Project Proposal Mycot Bigel.pdf [621708]

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PN-III-CERC -CO-PED -2-2019

FUNDING APPLICATION
„Innovative biobased bigel antimycotic formulations ” – MYCOT -BIGEL .

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PN-III-CERC -CO-PED -2-2019 B.2 Scientific description „Innovative biobased bigel antimycotic formulations ” – MYCOT -BIGEL
B. 2.1 Project Scope and Objectives
• Project scope, demonstration model to be developed and tested/validated
In the last peri od, disease related microorganisms exhibit an increase resistance to systemic antimicrobial
therapy and determine the use of more toxic drugs with obvious side -effects. Therefore topical antimicrobial
therapy, based on the absorbtion of high drug doses thr ough skin surface causing a reduction of microbial
proliferation at infected skin sites emer ges as an atractive alternative . Advantages of topical administration for
bioactive substances versus systemic one (parentheral, oral) reside in avoiding the enzymatic degradation and
rapid clearance in the gastrointestinal tract, reducing possible adverse effects, increasing patients compliance and
finaly reducing the treatment cost [1]. Topical delivery of antimicrobials requires new and improved
formulations with good encapsulation abilities of both hydrophilic and hydrophobic actives ensuring not only
skin penetration of these substances but also protection of skin barrier and avoiding of s ide-effcts such as atopic
dermatitis. Among these formulations for topical administration, recently developed bigels, superior to the
commonly used emulgels , are obtained by combining a hydrogel with an oleogel and possess characteristics of
both systems such as cooling effect, hydration of the stratum corneum, moisturizing and emollient effect,
spreadability, water washability after application [2]. Ratio of the constituent oleogel and hydrogel phases and
structural distributions of each phase allow manipulation of the bigels properties such as consistency, drug
release rate and stability [3, 4].
The aim of this proposal is formulation of innovative bigel systems based on biologically active oleogels and composite hydrogels containing antimicrobial silver microparticles with potential antimycotic activity
due to encapsulation of natural principles, Chelidonium majus L extracts and essential oils. The target of
antimycotic activity is a very extended affection of skin, Tinea pedis (Athletes’s foot disease) affecting 15 -20%
of the population, caused by three filamentous genera of f ungi, dermatophytes, such as Microsporum ,
Trichophyton and Epidermophyton, [5, 6]. Although systemic and topical treatments are available (drugs such as
Griseofulvin, Ketoconazone, Fluconazole, Terbinafine, etc) the increase drug -resistance reported for th ese fungi
and reported side effects determines the need for antifungal agents with low toxicity and high sensitivity, natural
actives being the most important [6]. The developed formulations resulted from this proposal combine the
advantages of biological activity of natural extracts with proved antimicrobial and antimycotic effects with the
biological activity and functional features of innovative bigels formulated from oleogel based on active
vegetable oils and composite hydrogels containing silver microparticles. Partners involved in this proposal have
initial experience (TRL 2) regarding all the components of the proposal as follows: UPB (Co) worked more than
10 years harnessing biologically active oils in lipid based carries loaded with synthetic and na tural actives and
formulation of organo- and oleogels; ICECHIM (P1) will use a previously developed concept of micro/nanogel
composites based on polyethylene glycol diacrylate (PEGDA) and natural zeolite and Plantavorel SA (P2) has
an extensive experience in the field of extraction and characterization of extracts from different medicinal plant
species. The final outcome of the proposal will be both validation of the laboratory technologies for the
preparation of bigels system based on mixture of microparti cle of hydrogel composites and organogels used as
controlled delivery systems of bioactive natural substances and laboratory technology for extraction of
phytocomplexes from Chelidonium majus L, in order to obtain innovative formulations with antimicrobial and
antifungal activity for potential applications in the pharmaceutical field (TRL4)
• Novelty and relevance of the preliminary results related to the project in relation to national and international state of the art
In the last five decades Tinea pedis (Athletes’s foot disease) has become a world wide epidemiological and
economic problem, although it is not life threatening, due to its high prevalence and its associated morbidity having negative consequences for patiens that may potentiallly undemine th eir work and social lives[5]. Tinea
pedis is caused mainly by dermatophytes such as Trichophyton mentagrophytes, Trichophyton rubrum,
Trichophyton tonsurans, Trichophyton interdigitale, Epidermophyton floccosum , etc. Infections may be
classified according to location: sole of the foot (vesicular), lateral aspects of the foot (moccasin) – the most
severe and chronic, between the toes (interdigital) – the most common. Left untreated, besides discomfort (e.g
itching) may lead to health complications such as secondary bacterial infections, immunological reactions and
perifolicular granulomatous inflammation [7]. Numerous treatment options are available, with topical treatments
as first line therapy but with supplementary oral antimycotics for extensive infection s. Due to the necessity of
treatment for an extended period of time, patients have a tendency to cease antimycotic administration when

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PN-III-CERC -CO-PED -2-2019 clinical symptoms have improved thus causing reinfection and relapse. Moreover, available antimycotic drug
therapies, alt hough efficient, may cause systemic toxic side effects, drug resistance [8] or in the case of topical
treatments, atopic dermatitis. As an addition, due to secondary infections it is beneficial for antimycotic drugs to have additional antibacterial activit y in order to avoid additional antibacterials in the treatment scheme [7].
Natural products with anti- dermatophytic activity represent a promising alternative for synthetic drugs in topical
treatment for Tinea pedis exhibiting excellent safety but their fo rmulation is important in order to compensate
volatility and instability and to enhance their antimycotic effect or to decrease skin irritability on topic
applications [6]. Suitable formulation of natural extracts and essential oils, due to the ability to carry substances
passing through the cell membrane determines improved biodisponibility. Essential oils, with their antimycotic
and antibacterial activity are amongst the most popular natural products recommended in treatment of topical
fungal infections, their activity and association being recently reported [9]. One of the most important essential
oil effective in topical treatment of mycoses is obtained from Melaleuca alternifolia (tea tree oil) playing a role
in the management of inflammatory/immune dis orders affecting the skin, with additional antioxidant and anti –
skin cancer activity. Antimycotic effect of tea tree oil against T. interdigitale is manifested at high concentrations
(25% and 50%) when used alone and only association with synthetic drugs decrease effective doses of tea tree
oil to 5% concentration. Although effective, several side -effects are reported such as skin irritation, allergic
contact dermatitis, systemic contact dermatitis, linear immunoglobulin A disease, erythema multiformelike
reactions, systemic hypersensitivity reactions, etc [10]. An explanation for these adverse effects may be the rapid
oxidation of components, mainly alfa terpinene (5- 13%) to skin allergens[11]. Atopic dermatitis is a type of
chronic eczematous skin inflammation with increased prevalence affecting 15 -30% of urban children and 1 to
3% of adults. A recent review paper evidenced the pharmaceutical and therapeutic advantages of the natural herbal medicines in the treatment of this skin affection [12]. Among all the investigated natural actives
Chelidonium majus L extract presented promising amelioration of atopic dermatitis symptoms. Taking into
account the major drawbacks of tea tree oil, the antimycotic activity of other essential oils has to be investigated and evaluated.
Based on these previous reported results the present proposal intent to use in innovative bigel formulation of
hydrophobic Foeniculum vulgare L (fennel ) essential oil ( FVeo ), in combination with hydrophilic
phytocomplexes extracted from Chelid onium majus L (celadine, CMpc ). This association of natural active
principles is sustained by reported literature data on their antimicrobial and antimycotic activity: (a) FVeo
exhibit stronger antimycotic activity against T. tonsurans, T. menagrophytes and T. rubrum than common
antifungal drug amphotericin B and fluconazole. This effect may be explain by damage of the intracellular
organelles and plasma membrane and inhibition of mitochondrial enzyme activities [13, 14]; (b) CMpc
antibacterial and antimyco tic activity is attributed to constituent alkaloids, flavonoids and phenolic acids,
different extracts and individual components being investigated [15]. Although the effect of CM extracts on
pathogenic fungi (e.g. Candida sp., Trichophyton sp) was signifi cantly weaker compared to the effect on
pathogenic bacteria ( Bacillus cereus, E. coli, Pseudomonas aeruginosa, S. aureus) the combination of these
activities is beneficial for the innovative bigel formulations aimed by the present proposal, as mentioned ab ove
formulation of natural actives having a great impact on their stability and biological activity.
The novelty of the present proposal is the use of biocompatible, biologically active ingredients for the
components of bigel formulations which are expect ed to enhance the antimicrobial and antimycotic activity of
the natural active principles ( FVeo and CMpc ) not only by improving the topical drug- delivery features but also
by the additional biological effect of vegetable oils in oleogels and silver micropa rticles in composite hydrogels.
The oleogel component of the innovative bigel formulations will be obtained from biologically active vegetable
oils such as Nigella sativa (black cumin) seed oil ( NSO ) and Echium plantagineum (viper -bugloss ) oil ( EPO )
with b iocompatible organogelators such as beeswax, monoglyceril stearate, sorbitan derivatives, etc. The
selection of these components was made taking into account the reported literature data. NSO has antibacterial
and antimycotic activity attributed to the pre sence of thymoquinone identified in cold- pressed oil in 3.5-8.7 mg/g
concentration [16], the MIC of thymoquinone constituent of NSO was found to be 0.05 mg/ml for all tested
dermatophytes [17], additional anti-histaminic, anti -oxidant and anti -inflammatory effects of NSO being also
reported [18]. Moreover, NSO is mainly composed of unsaturated fatty acids, the highest amount represented by
linoleic acid, LA, 55% which plays an important role in statum corneum , being one of the main components of
the ceramid es constituents of the lipid layer, preventing the peeling of skin and transepidermal water loss
(TEWL), thus improving skin softness and elasticity and regulating the process of epidermal keratinization [19].

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PN-III-CERC -CO-PED -2-2019 Echium plantagineum seed oil ( EPO ) is enriched in highly unsaturated fatty acids (~14% linoleic acid, LA, 10%
gama – linolenic acid, GLA, 33% alfa -linolenic acid, ALA and 14% stearidonic acid, SA) with important
biological anti inflamatory activity and benefits when applied to skin [20, 21]. Topical administration of GLA
and LA rich vegetable oils help rehydrate and restore the skin and can provide assistance in dispatching on the
signs of aging, but also are very effective in preventing and treating inflammatory conditions and skin disorders
such as eczema and dermatitis [22]. The high content of EPO in stearidonic acid, SA, ~14% is considered to be
responsible, when administrated to skin cells, for two third inhibition of Prostaglandin E2 (PGE2) release as
compared to untreated tissue [23]. PGE2 is responsible for regulation of inflammatory responses and promotes
allergic contact dermatitis [24]. This concept of associating the therapeutic effects of synthetic and/or natural
actives with the biological effects of vegetable oils has been already exploited by UPB(CO) group in
formulating nanostructured lipid carriers, NLCs containing vegetable oils able to encapsulate synthetic antifungal drugs (Nystatin) and vegetable actives such as basil essential oil [25], laurel leaf essential oil [26] and
carrot extr act [28] with proved actions in the prevention of cellular damage [26], carotinoids mixture [27] and
luteine [29] as valuable nutraceutical supplements. The concept was extended to other types of carriers, hybrid PLGA nanoparticles with NSO oil able to encapsulate a lipophilic antimicrobial drug [30] or NSO and EPO oils
based hybrid PLGA nanoparticles decorated with PEG with improved performances in anti -inflammatory drug
Indometacin delivery [31].
The composite hydrogel component of innovative bigel form ulations is based on previously developed
concept by ICECHIM Team of micro/nanogels composites based on polyethylene glycol diacrylate (PEGDA)
and natural zeolite [32]. The embedding of silver nanoparticles with established antimicrobial and antimycotic
biological effect [33-38] and encapsulation of CMpc will lead to improved biological activity for the designed
formulations. Chelidonium majus L phytocomplexes, CMpc with antimycotic activity will be obtained and
characterized by Plantavorel SA (P2) team according to their well -established competences: phytochemical and
microbiological screening, selective extractions/conditioning of the phytocomplex in different preparations;
qualitative and quantitative analyses of active principles in aromatic and medicin al plants, algae and fungi,
obtaining and physical and chemical characterization of some extractive fractions with therapeutic potential; development of original technologies, modern and environmentally superior to allow processing of medicinal
plants; extracts conditioning; development of standardized, efficient and safe bio- products.

In conclusion, the novelty aspects that arise from the present proposal are provided by implementing the
following specific objectives:
I. Design of the technological models for components of biobased bigel antimycotic formulations:
vegetable oils (NSO and EPO) based oleogels, PEGDA – microparticle of hydrogel composites with silver
microparticles HC -Ag, phytocomplexes from Chelidonium majus L ., CMpc
II. Elaboration and vali dation of laboratory technologies for the preparation of biobased bigel
formulations loaded with antimicrobial and antimycotic natural actives, Foeniculum vulgaris L , essential
oil, FVeo and antimycotic phytocomplexes from Chelidonium majus L ., CMpc

III.Elaboration and validation of laboratory technology for the extraction of Chelidonium majus L . CMpc
phytocomplexes and phytochemical evaluation.

The proposal working hypotesis envisage innovative strategies which will solve the main drawbacks underlined
in the literature and will lead to the development of topical innovative formulations with antibacterial and
antimycotic activity, targeting Tinea pedis with the scope of reducing the side effects of classical drugs
formulations and increased therapeutic ef ficiency:
1) The use of natural active compounds against dermatophytes, Foeniculum vulgare L. essential oil, FVeo and
Chelidonium majus L. phytocomplexes, CMpc with reduced risk of developing drug resistance;
2) The use of active ingredients in the formul ations, silver microparticles and biologically active vegetable oils
(NSO and EPO ) aiming a synergistic effect with FVeo and CMpc
3) The use of innovative bigel formulations that will enhance the biodisponibility of both hydrophilic and
hydrophobic natur al active principles and will protect skin of reported side efects of clasical synthetic drug
topical formulations.

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PN-III-CERC -CO-PED -2-2019 • Presentation and argumentation of TRL value
Technological Readiness Level 2 (TRL 2) for the innovative formulations from biologically activ e vegetable
oils has been already accomplished by the UPB (CO) group through publications and patents associated with
obtaining of other lipid carriers able to encapsulate different natural actives with demonstrated in vitro
aplicability in food, cosmetic and pharmaceutical fields [25-29, 40 -42]. The envisaged vegetable oils , NSO
and EPO have been already involved in developing innovative hybrid PLGA drug delivery systems with
improved encapsulation and release properties [30 -31]. Moreover the concept of association of a synthetic
antimicrobial drug with an biologically active essential oil [25] or an inorganic antimicrobial (TiO 2) [39]
proved to be succesful in antimicrobial and antifungal formulations. So, formulation of technological concept
(TRL2 ) of h ybrid formulations based on vegetable oils and natural actives is acchieved. These models for
oleogels based on NSO and EPO loaded with FVeo and corresponding bigels co-loaded with FVeo and CMpc
will be developed at laboratory scale (TRL3 ), the obtained f ormulations will be completelly characterized and
demonstation of their functionality as delivery vehicles for bioactive natural extracts as well as their antimycotic
activity will be achieved. Finaly the elaborated laboratory technology for innovative bio based bigel
formulations loaded with natural antimicrobial and antimycotic actives will be validated and homologated
(TRL 4 ).
The other component of innovative bigel formulation that will be developed by ICECHIM (P1) group refers
to designing innovative po lyethylene glycol diacrylate (PEGDA) microparticle of hydrogel composites which
contains silver microparticles for the preparation of bigels system with antimicrobial and a ntimyc otic activity for
potential applications in the pharmaceutical field . For this matter, the project uses a previously developed
concept of micro/nanogels composites based on polyethylene glycol diacry late (PEGDA) and natural zeolite .
Proposed demonstration model (from TRL 2 to TRL 4 ). The project focuses on up -grading the concept of t he
innovative microparticle of hydrogel composites for the preparation bigels system used as controlled delivery
systems of bioactive natural substances as phytoextract solution with antimicrobial and antifungal activity for
potential pharmaceutical applic ations (TRL 3) and testing the innovative bigels system based on mixture of
microparticle of hydrogel composites and organogels (TRL 4). The project on- set refers to micro/nanogels
composites bas ed on polyethylene glycol diacr ylat (PEGDA) and natural zeoli te and natural bioactive
substances –TRL 2, developed on project TE44/2015 BIOGELFARM). Starting from this point, the project
targets first the upgrade of this concept, with the addition of silver microparticles to generate microparticle of
hydrogel compos ites which contains silver microparticles system with antimicrobial activity used as controlled
delivery systems (TRL 3 ). The formerly mentioned TE 44/2015 project assumes the preparation
micro/nanoparticles of covalently crosslinked hydrogels based on pol yethylene glycol diacrilate (injectable
micro/nanogels) consists of the embedding in their structure of natural nanozeolites but also of natural bioactive
substances, with potential pharmaceutical applications, and, herein, the final microparticle of hydro gel
composites will be achieved by poly(ethylene glycol) diacrylate ( PEGDA ) oligomer polymerization in the
presence of silver microparticles in aqueous environment in the presence of redox – initiation systems . The
polymerisaton is in fact a cross -linking reaction which takes place in the inverse microemulsion by dispersing the
aqueous solution of reactants in an organic liquid immiscible with water, in the presence of an emulsifier . The
technologies for the preparation bigels system based on mixture of microparticle of hydrogel composites and
organogels used as controlled delivery systems of bioactive natural substances with antimicrobial and
antifungal activity for potential applications in the pharmaceutical field will be thus validated (TRL 4) .
The tec hnological concept for the extraction o phytocomplexes from Chelidonium majus L and experimental
model on laboratory scale ( TRL 2 ) is based on the previous experience of Plantavorel (P2) group i n the field of
extraction and characterization of natural acti ves from different medicinal plant species is attested by the projects
carried out in the field, published works and communications at scientific events. The model ( TRL 2) will
consist of preliminary reasearch activities such as conitioning of starting mat erials, selection of extraction
solvents, selection of analytical and control methods, establishing of laboratory protocols for extraction of
phytocomplexes from CM , phytochemical screening of extracts. TRL 3 phase will be achieved by elaboration of
labora tory extraction technology with selection of the most suitable solvents, comparative studies of extraction
using clasical and unconventional procedures for That will ensure extraction of the envisaged bioactive
compounds. Finally validation of elaborated e xtraction laboratory technology for phytocomplexes from
Chelidonium majus L . wiil be achieved ( TRL 4)

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PN-III-CERC -CO-PED -2-2019 B.2.2. Presentation of the concept of technology/product or existing model which constitutes the starting
point of the project
• Preliminary experimental results available prior the project application
The present proposal represents a continuation of the main research topics developed by the UPB (CO) team by
exploiting the functional and biologic activity of vegetable oils in innovative formulations efecti ve as drug
delivery vehicles for synthetic drugs, natural extracts or essential oils. Thus the synthesis and characterization of
novel nanostructured lipid carriers based on vegetable oils (grape seed oil, fish oil, raspberry seed oil, rice- bran
oil, pomeg ranate seed oil, amaranth oil, hemp seed oil, etc) encapsulating synthetic antifungal drugs (Nystatin)
and vegetable actives such as basil essential oil [25], laurel leaf essential oil [26] and carrot extract [28] with proved actions in the prevention of c ellular damage [26], carotinoids mixture [27] and luteine [29] as valuable
nutraceutical supplements. The fatty acid composition of vegetable oil and presence of other lipid actives, for example squalene, influence not only the overall biological activity of the formulation but allows co-
encapsulation of active principles lipophilic and hydrophilic – synthetic drug Pemetrexed and natural compound
Hesperidine achieving a dual sustained release of both actives from the same delivery vehicle [43]. The briefly
summarized research activities demonstrate that vegetable oils and phytochemicals have an important role in
developing new lipid based drug- delivery systems in order to develop innovative, safe commercial formulations
with multiple pharmacological effects .

National patents – in the framework of the
present proposal Research grants

Lacatusu, M.N Badea., LGR Stan, A Hanganu, A
Meghea, Nanoparticule lipidice antioxidante si
procedeu de obtinere a acestora , RO128703-B1,
2018 PN-II-PT-PCCA -2013 -4-1761 – project aimed to synthesize advanced and
functiona l nanocarrier systems based on Hemp oil, Linseed oil, Safflower oil
and Wheat Germ oil and loaded with selective natural extracts (e.g. Marigold
extracts, Carrot extract) and to explore their efficiency in developing safe bio –
cosmetic products with anti -acne properties.
G Niculae, I Lacatusu, M N Badea, R Stan, A
Meghea, Lipid Nanocarriers Based on Vegetable
Oils with Photoprotection and Antioxidant
Properties, RO130098-B1 , 2018 PN-II-ID-PCE -2012 -4-0111 – involved the c o-encapsulation of plant extracts
in b ioactive nanostructured lipid carriers which are able to release two
bioactivecompounds originated from ivy leaf extract and willow bark extract .
The main objective was to develop new pharmacological formulations based
on medicinal extracts with enhanced a nti-inflammatory performance.
G Badea, N Badea, N Bordei, D Istrati, I Lacatusu,
A Meghea, L Moldovan, I Panteli, M Popescu, I
Rasit, R Stan., Lipidic Nanotransporters Charged
with Vegetal And Synthetic Active Principles
Providing Amplified Anti -Inflammat ory Effect ,
Patent Number(s): RO131955 -B1, 2019 -Synthesis of New Organogelatorss with complexing properties suitable for
production of metallic naniwires”, CNCSIS 1427, 2004-2006
-Synthesis of nanostructured silica mediated by organogelators, 2007- 2008
-Synthesis of Low Shrinkage Dental Materials Mediated by Organogelators PCE ID_1718, 2009 -2011

The use of vegetable oil was extended by UPB (CO) team to other delivery systems, namely hydrophilic PLGA
nanoparticles in developing hybrid PLGA -vegetable oi l carriers with enhanced ability to encapsulate
hydrophobic drugs with antimicrobial [30] and anti -inflammatory [31] activity, respectively. In designing these
formulations the biological activity of the involved vegetable oils (also envisaged in this prop osal), antimicrobial
(NSO ) and anti -inflammatory ( EPO ), respectively, was considered and the same dependence of encapsulation/
release performance on the fatty acid composition of vegetable oil was observed.
Earlier research activities of the UPB team were devoted to synthesis and characterization of new
organogelators and exploiting their ability as structure directing agents in the preparation of nanostructured
inorganic materials and performant polymers.
The prior research activity of ICECHIM (P1) team includes developement of the concept of micro/nanogels
composites based on polyethylene glycol diacrylate (PEGDA) and natural zeolite , with potential use as drug
delivery vehicles [32] using the mini -emulsion polymerization technique [44]. The team experti se in the
polymeric based hydrogels is sustained by elaboration of biocomposites based on acrylic gels [45] triblock
copolymers of poly(ethylene glycol) (B) and copolyacrylates of oligo(ethylene glycol)s [46], etc.

International, National patents , patent s applications – in the
framework of the present proposal Research grants
A.Sarbu, A. -L Ciripoiu., A Lungu ., F.Bacalum, L.Sarbu, M. Bombos,
Process for the obtaining of hybrid polymer inorganic -organic
nanocomposites based on natural or synthetic zeolites and BIOGELFARM Nr. 44/2015 ( PN II – Human
Resources Programme – Young research teams 2014)
„New drug delivery systems based on micro/nanogel

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PN-III-CERC -CO-PED -2-2019 polyacrylonitrile, EP 2505596B1/02.03.2016 composites containing natural bioactive substances
A Zaharia, A-L Rad u, A Sarbu, M Teodorescu, B Cursaru, C P
Spatarelu,T.V Iordache, T. Sandu, AM Florea “ Nanohydrogels for slow
release of drugs and process for preparaing the same A 2016 – 00105 /
07.09.2016
A-L Radu, A Zaharia , A Sarbu, M Teodorescu, B Cursaru, C P S patarelu,
T., Sandu “ Inorganic -Organic Hybrids based on nanozeolites and
Nanogels for Controlled Release of Drugs and Process for Preparing the
Same, A 2017 -00105 / 23.02.2017 PLAnano, Nr. 91/2018 „Ligand -free targeted delivery
nanogels for phospholipa se A2 retentio n

Previous experience of Plantavotel SA (P2) team in the field of extraction procedures [50], characterization of
selective components [47, 49], authentication [48] and phytochemical evaluation [51- 53] of phytocomplexes
from different medic inal plant species is attested by publications and patents and eveloped research projects

National patents applications – in
the framework of the present
proposal Research grants
S Apostol, S Iancu, E.Ionescu, A. L
Radu, Sandu T, A.Sârbu, A.Stoica,., M.
C., Stroescu, C. Tebrencu , Zaharia A,
“Process for Preparing Hybrid
Hydrogels Containing Bioactive
Phytoextra cts”, RO132253-A2;
A/00365 / 23.05.2016. Project PN -III-P2-2.1-PED -2016 -1604 – Research contract 192PED/2017 –
”Advanced and emergent technologies to obtain vegetal extracts used in innovator food
supplements ” – TEVIS , 2017 -2018;
PN-II-PT-PCCA -2011 -3.2-0548 – Exploitation of spontaneous flora resources by
nanotechnology for the obtaining of high bioactive hypericin concentrates
Project CEEx -AGRAL – Research contract 15/2005 – „ Characterization of some plant
and fungal bioactive principles with cytostati c, immunomodulatory, metabolic and
neurotropic actions and its application in functional food ”, 2005 -2008,

• The expertise of experienced researchers and postdoctoral researchers from the project team
UPB (CO) team: the project leader, Prof.Ph. D.Habil. Ra luca Stan (U-1700 -038G -7870) , h-index 9, has
extended professional experience in the field of organic chemistry, molecular organized systems, nanostructured
materials, exploiting natural compounds (e.g. vegetable oils) for preparation of performant materia ls and drug
delivery systems – subject of the habilitation thesis UPB 2016. She is the author of 4 books and 3 book chapters
(2 international), 67 scientific publication (57- ISI), co -author of 3 national patents and one patent application,
director of 6 n ational research grants and participant in other 18 grants. In the domain of the project – 1
international book chapter regarding authentication of vegetable oils [54], 8 ISI papers [25- 31, 39], 3 national
patents [40 -42]. Assoc prof. Ph.D.Habil Ioana Laca tusu, key person ( U-1700 -036U -0780) h -index14, has an
extensive experience in formulating lipid based nanocarriers, author of 26 ISI papers and 3 national patents in
the field of the project. Assoc prof. Ph.D Habil Nicoleta Badea, key person,( U-1700 -039Z -0057) h -index17
extensive experience in formulating and characterization of lipid based nanocarriers (26 ISI papers, 3 national patents), preparation and characterization of silver nanoparticles generated in the presence of different
phycomplexes (5 ISI papers). Lect . Ph.D Brindusa Balanuca (U-1700- 037R -3224 ), has a significant experience
in synthesis and characterization of functional organic compounds and polymers based on vegetable oils
specialist in characterization of vegetable oils and TGA, DSC, FT -IR, UV -Vis analyses, her research domain
being at the interface of organic synthesis and materials science. The expertise related to the project topic is
highlighted by 9 ISI papers. The other members of UPB team are: Lect . Ph.D Cristina Ot t, (U -1700 -035X –
0271 ) – specialist in preparation of oleogel/ bigel sistems , 7 ISI paper – lipid based carriers, 3 ISI papers
organogelators, Ph. D . Andrada Serafim (U-1700- 036L -5550) specialist in rheological characterization , 23 ISI
papers. The Ph.D , students (R. Stan scientific advisor) involved in the project, Emilian Ghibu (U-1900 -062J –
0196), Elena Danila (U-1700- 038Q -0223) and Alina Morosan (U-1700- 037Z -8078) are involved in synthesis
and characterization of the materials developed in the proposal, with at least 1 I SI paper in the project domain.
ICECHIM (P1) team – person in charge- SR.I. Ph.D Anamaria Zaharia (U-1700- 039U -3018), h-index7, 1
Book Chapter, 30 ISI and 2 non -ISI articles, , 1 European Patent, 4 National Patent and 9 National Patent
Claims, 2 research gr ants as leader in the field of the proposal, 2 as ICECHIM person in charge, 15 grants as
participant, 5 International and 5 National awards for Inventions and research results. SR I .Ph.D . Andrei
Sarbu (U-1700 -038H -2911) h -index13, outstanding expertise i n the field of synthesis, chemical modification,
characterization and processing of polymers and biopolymers, 90 ISI articles, 4 book chapters, 32 Patents (from which 1 European) and 18 patents applications. SR I, Ph.D . Tanta Verona Iordache ( U-1700- 039T -3246), Key
person, h-index 9, research domains molecularly imprinted polymers, innovative materials for waste -water

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PN-III-CERC -CO-PED -2-2019 purification systems, host -guest synthesis of hybrid polymer nanocomposites for water and soil protection, and
biosensors development, 31 ISI publications, 1 book chapter, author of 2 patents and 9 patent applications,
project leader for 2 national and 2 international grants, person in charge for 1 national grant.
SR1 Ph.D. Anita -Laura Chiriac (Radu) (U -1700- 039M -2871), Key person, h-index 8, S pecialist in Composite
Hydrogels Preparation, X -Ray Diffraction (SAX/USAX, GIXRD), 1 book chapter, 30 ISI and 10 non -ISI
articles, 6 national and 1 European patents, 10 patent applications, 4 research grants as leader and 1 as person in
charge. Participati on in 22 national, 2 bilateral, 3 inter -academic, 5 European projects. The expertise of the other
persons involved in the project is detailed in section B2.3
PLANTAVOREL S.A. (P2) team- person in charge – SR. 1 Ph.D. Carmen Elena Țebrencu (U-1700- 033B –
6117), research interest: phytochemical study of plant species; exploitation of indigenous medicinal plants,
phytochemical screening of plants and plant extracts; extraction of p lant metabolites: development of original
technology, modern and environmentally superior for processing of medicinal plants; 60 scientific papers, 15 patents, 9 research project as coordinator and 26 as key person, international and national prizes for pa tents and
scientific results. SR.1 Ph.D Elena Ionescu, (U-1700- 033B -0852), Key person, member of Academy of
Romanian Scientists. Research interest: kinetic and thermodynamic studies; mass transfer and thermal
equilibrium; equipment and flow optimization through mathematical modeling technology, advanced purification, residual gas purification and wastewater treatment, vegetable raw materials research and
processing, active phytocomplex conditioning; 1 book, 63 scientific papers, 40 patents 38 national grant s, 4 as
leader and 1 as, person in charge; international and national prizes for patents. M ember of « International
Alliance of Dietary/ Food Supplement Associations” and “European federation of Associations of Health
Product Manufacturers”, Belgia, “Associ ation for the Medicinal & Aromatic Plants of Southeast European
Countries” Austria, “Society for Medicinal Plant Research and Natural Product Reseach”, Germany. Eng Oana
Teodora Ciupercă, Ph D student, (U -1700 -036Z -7086) Key person , Specialist in phytochem ical studies on
medicinal and aromatic plants , investigation of antioxidant activity, UV-VIS and FT -IR Spectrometry, data
interpretation/processing and dissemination activities, 10 scientific papers (2 ISI) participant in 10 research
grants. The expertise of the other persons involved in the project is detailed in section B2.3.

B.2.3. Method of project implementation
The work plan of MYCOT -BIGEL proposal is structured in 3 work packages , WPs and specific activities taking
into consideration the project specific goals. Team members are implicated in activities according to the
competences presented in a Table below. All the staff will be involved in dissemination (A1.8, A2.9 and A3.5).
The project leader and the key persons will be involved in Homologation of the technology innovative bigels,
A3.5 as well as intellectual property protection A 2.9.
WP1. Researches on technological model for components of biobased bigel antymycotic formulations (M1 –
M8, TRL2) .
A.1.1. Formulation and characterization of oleogel s based on vegetable oils with natural or/and synthetic
gelators for innovative bigel formulations (CO-UPB ). Formulation of NSO and EPO oleogels with
biocompatible gelators. Optimal synthetic conditions established by varying nature and gelator concentrati on,
mixing time, temperature, post treatment. Characterization of NSOg and EPOg : structure by FT -IR, thermal
behaviour by DSC, morphology by polarized microscopy and SEM, viscosity, deformation by rheology.(M1-
M5, RS, BB, CO, AS, EG, ED)
A.1.2. Formulation and characterization of selected biobased oleogels loaded with antimycotic FVeo (CO –
UPB ) The most performant NSOg and EPOg oleogels will be loaded with different amounts of FVeo
(composition assesed by GC -MS), characterization of NSOg -FVeo and EPO -FVeo (FT-IR, DSC, microscopy,
rheology), encapsulation eficiency and controled release studies (Frantz cell, UV -vis, HPLC – MS) .(M6 -M8, RS,
IL, NB, BB, CO, AS, EG, ED, AM).
A.1.3. Up- grading the Concept of micro/nanogels composites based on PEGDA and natural ze olite to PEGDA –
microparticle of hydrogel composites with silver microparticles HC -Ag for the preparation of bigels system with
antimicrobial activity (P1-ICECHIM ): Synthesis of microparticles of HC-Ag by polymerization of PEGDA
oligomer in the presence o f commercial Ag microparticles in aqueous environment with redox – initiation systems
using the previously developed inverse microemulsion technique [44] . Optimal synthetic conditions will be
established varying the nature of the dispersion medium, type of emulsifier, the organic solvent/aqueous phase

9
PN-III-CERC -CO-PED -2-2019 ratio, the emulsifier/aqueous phase ratio, the mode of stirring and the reaction time . (M1-M6, AZ, AS, VI, TS,
MD, AC, RB, AI, ED)
A.1.4. Physico- chemical and morphological characterization of microparticle s of HC-Ag for the preparation of
bigels system with antimicrobial activity (P1-ICECHIM ). Complete characterization of HC-Ag: a.
Dimensionally – particle size, assembly, polydispersity index, zeta potential – DLS; b. Rheology; c. Structural –
NMR, FTIR, d. Morphology and porosity- TEM, BET e. Thermal and mechanical properties – TGA and
DSC(M7 -M8, AR, RI, MG, LC, AM, MD, SA, MB, BT, CC).
A.1.5. Formulation of technological concept, experimental laboratory model for antimycotic phytocomplexes
from Chelidonium m ajus L.( CMpc ).(P2-Plantavorel ) Preliminary actions for laboratory model: vegetable
starting material (aerial parts and roots) conditioning and investigation, selection of extraction solvents, selection
of analysis and control methods, laboratory protocols for characterization of vegetable starting materials,
extraction of phytocomplexes, testing and demonstation of the extraction technology.(M1- M3, TCE, IE, COT,
CM, PCF, PM, CL)
A.1.6. Phytochemical screening for antimycotic phytocomplexes from Chelidonium majus L (P2- Plantavorel)
Evaluation and quantification of phenolic , alcaloid, flavonoids components by HPTLC and UV -vis (M4 -M8,
TCE, COT, CI, IE, CM)
A.1.7. Evaluation of biological antimycotic activity of CMpc and FVeo (P1-ICECHIM) The antimycotic
susceptibility test of the actives CMpc and FVeo will be performed by a broth microdilution method in
agreement with the EUCAST recommendations on T. mentagrophytes, T. t onsurans, M. Canis and M. gypseum
from P1 collection. (M6- M8, LJ, MA, AG, IC, IR, CM)
A.1.8. Dissemination of research results by communication at National and International Scientific Conferences
– realized by partner CO and P1 and P2: 3 communications. Deliverables : Preparation Methodologies and
Product Sheet for NSOg , EPOg and NSOg -FVeo and EPO -FVeo, respectively , Preparation Methodologies and
Product Sheet for HC -Ag, Experimental model and product Sheet for CMpc , Report of biological test with Fveo
and CMpc . Milestone: Procedures for preparation of Oleogels and FVeo oleogels, Procedure f or preparation of
HC-Ag , Laboratory experimental model and analytical report for CMpc (M8)
WP2 Elaboration of the laboratory experimental demonstrator of the technology for obtaining of
biobased bigel formulations with antimycotic activity M9 -M20 (TRL3)
A.2.1 Laboratory technology and characterization of biobased oleogels loaded with antimycotic actives (CO-
UPB) Laboratory technology for NSOg and EPOg unloaded and loaded with FVeo will be established based on
the experiments of WP1. Selection of final pa rameters based on best functional determined by complex
characterization (M9 -M14, RS, IL, NB, BB, CO, AS, EG, ED, AM)
A.2.2. Laboratory technology for innovative antimicrobial microparticle of hydrogel composites loaded with
CMpc with antimycotic activity (P1-ICECHIM ). Study on the encapsulation of CMpc in microparticle s of HC-
Ag, by: a. Direct adsorption by the microparticle of HC-Ag from CMpc solution until the maximum degree of
swelling is reached and b. Obtaining of HC -Ag microparticle directly in the CMpc solution. Encapsulation
efficiency determination and presence of the encapsulated phytocomplex evidenced by FTIR spectroscopy (M9 –
M17, AZ, AS, VI, TS, MD, AC, RB, AI, ED),
A.2.3. Study on the capacity of controled release and physico- chemical and mor phological characterization of
microparticle of hydrogel composites loaded with antimycotic actives (P1-ICECHIM) Study of controlled
release of CMpc from HC-Ag microparticles in saline phosphate buffer (PBS) by UV -vis spectroscopy or
HPLC coupled with ref ractive index, by conductivity and by pH measurements (M18- M20, AZ, AR, RI, MG,
LC, AM, MD, SA, MB, BT, CC)
A.2.4. Extraction studies of antimycotic phytocomplex from Chelidonium majus L., CMpc – laboratory phase
(Plantavorel -P2) Selection of extraction so lvents, processing of vegetal material experiments, obtaining of raw
vegetable extracts, selective extraction methods, conventional at different temperatures and sonication, MW
(M9- M16, TCE, IE, PCF, BGE, PM, CL, MM, BE, JC, PA)
A.2.5.Elaboration of labo ratory technology for the extraction of CMpc and phytochemical evaluation
(Plantavorel -P2). This activity will establish the functionality and utility of the laboratory technology for CMpc
extraction highlighting the pass from TRL2 to TRL 3. The reproducib ility of the extraction protocol will be
confirmed by repeated experiments. Quantification of composition of elaborated CMpc , by HPTLC, UV -vis
using specific methods for polyphenols, flavonoids, alcaloids, etc. (M17- M20, TCE, IE, PCF, BGE, PM,
CL,COT, CM, CA, DM)

10
PN-III-CERC -CO-PED -2-2019 A.2.6. Elaboration of laboratory technology for the preparation of biobased bigel formulations loaded with
antimicrobial and antimycotic natural actives (CO-UPB ) Synthesis of innovative bigels by combination of
NSOg -FVeo and EPOg -FVeo with HC-Ag-CMpc . Technological parameters: oleogel:hydrogel ratio,
temperature, post treatment, homogenization procedure, additional additives. (M15- M20, RS, IL, NB, BB, CO,
AS, EG, ED, AM);
A.2.7. Evaluation of biological activity of innovative bigel formulations l oaded with antimicrobial and
antimycotic actives (P1-ICECHIM ) – antimycotic susceptibility test of bigel co -loaded with CMpc and FVeo
will be performed by a broth microdilution method in agreement with the EUCAST recommendations on T.
mentagrophytes, T. to nsurans, M. Canis and M. gypseum from P1 collection. (M19- M20, LJ, AG, MA, IC, IR).
A.2.8. Complex functional characterization of innovative biobased bigel formulation loaded with natural
antimicrobial and antimycotic actives ( CO-UPB , P1 -ICECHIM ) Control led release studies- UV-vis, HPLC –
MS, rheology, morphology – SEM,TEM, Structure – FT-IR, XRD, Thermal properties – DSC) (M18 -M20, CO –
RS, IL, NB, BB, CO, AS, EG, ED, AM, P1- RI, AR, BT) A.2.9. Dissemination of research results by
communication at National and International Scientific Conferences and publication of 2 papers in ISI journals
Intelectual property rights – submiting of a national patent application for the bigel formulations (realized by
partner CO and P1 and P2, 2 ISI articles, 2 communications ,1 patent application)
Deliverables: Experimental reports, innova tive laboratory technology for oleogels, HC -Ag and bigels, from, 2
scientific communications, 2 ISI sent articles. Milestone : Laboratory technology for preparing FVeo loaded
oleogels, HC-Ag-CMpc microparticles and innovative bigels loaded with anti microbial and anmycot ic actives;
Laboratory technology for extraction of CMpc ; Demonstration reports for all elaborated technologies (M 20)
WP3. Laboratory validation of the elaborated technology for biobased bigel formulations loaded with
natural antimicrobial and antimycotic actives M21 -24 (TRL4)
A.3.1. Validation of the laboratory technology for biobased oleogels loaded with FVeo (CO-UPB, M21- M22) ;
A. 3.2. Validation of the laboratory technology for innovative composite hydrogels loaded with CM pc (P1-
ICECHIM M21- M22); A.3.3. Validation of the laboratory technology for innovative biobased bigel
formulations loaded with natural antimicrobial and antimycotic actives (CO-UPB M22- M23); A.3.4.Validation
of elaborated extraction technology for CMpc (P2-Plantavorel ) A. 3.5 Homologation of laboratory technology
for innovative biobased bigel formulations loaded with natural antimicrobial and antimycotic actives ( CO, P1,
P2, M24) A.3.6. Dissemination of research results by communication at National and Int ernational Scientific
Conferences and publication of 2 papers in ISI journals with impact factor ≥ 2 . Deliverables : functional model:
validated laboratory technologies for oleogels, composite hydrogel, bigels, CMpc,. Milestone : Homologation of
laboratory t echnologies. ( M 24)
Project management – permanent activity (M1 -M24) performed by project leader in collaboration with P1 and
P2 based on proven project management methodologies : (i) Organisation : clear definition, agreement and
update of roles and respo nsibilities; (ii) Planning : preparation of an achievable and agreed statement of what the
project is going to produce, when and how it is to be produced and assigned to the different Tasks; (iii) Controls :
regular review of the status and update of the wor k plan. Quality Reviews : identification of errors in end-
products by means of a planned and documented inspection, ensuring that all deliverables are of acceptable
standard before delivery
Dissemination of results : 4 papers in ISI journals with FI>1.5, 5 communications , 1 patent application .
Intellectual property protection of the original aspects by patents: In this direction will be applied and owned
only by the research partners (UPB and ICECHIM) and could be transfered in the legal conditions to the
industrial partner (Plantavorel). Authors could be from all 3 partners. The patents will reflect the contribution of
each research partner to each new solution. ,This contribution will be agreed in written by the research
partners. All patents will be owned jointly by the 2 research partners . The partner having the biggest
contribution to the patent will apply for it, after signing a convention of ownership sharing with the other partner.
In case that no written agreement is reached about the contribution o f each research partner to the patent, the
patent will belong to the 2 research partners in equal percent of 50% and the application will be made by the coordinator. The problem of all aspects about the intellectual property, according to the law, will be clearly
established in the partnership agreement, in the case of grant approval. At least 1 patent will be applied for.

Gantt Chart with planned activities of MyCOT -BIGEL during the project implemention

11
PN-III-CERC -CO-PED -2-2019

Research Infrastructure available for implementa tion of proposal
Nr
crt Laboratory Equipments ERRIS
UPB(CO)
Organic Synthesis
and Structural
Analysis Laboratory
OSSAL . The High Resolution Fourier -Transform Ion -Cyclotron -Resonance (FT -ICR)
Spectrometer, SolariX XR 15T, Bruker Daltonics , equipped with ESI, APCI
ionisation and infusion direct sample introduction, GC, HPLC, MALDI imaging
systems. FT-IR Spectrometer with microATR accesory and Raman module ;
•UV-VIS Spectrometer; Gas chromatograph coupled with mass spectrometer
(quadrupole) ; Gas chromatog raph coupled with ion trap mass spectrometer
(MS/MS) ; High performance liquid chromatograph with diode array UV -VIS
detector and fraction collector ; Automated polarimeter ; Optical microscope
equipped for phase contrast and fluorescence imaging ; Polariz ed light optical
microscope ; Melting point apparatus (Boetius); Preparative liquid
chromatography system (MPLC) ; Laboratory centrifuge; Spin coater ; Muffle
furnace (max. 1100 deg. C) ; Tube furnace ; Schlenk inert gas/vacuum lines ;
Computer cluster for computational/theoretical chemistry ; Photochemical
reactor with Hg medium pressure UV lamp (150 W) ; Screen printing machine https://erris.gov.ro/O
SSAL
Research Centre for
Environmental
Protection and
Friendl y
Environmental
Technologies –
CPMTE Spectrophotometer UV -VIS-NIR ; Atomic Absorption Spectrometer
TOC/TN Analyzer ; Gas Chromatograph – DANI ; High Performance Liquid
Chromatograph (HPLC) ; Gas chromatograph with mass spectrometer
Ion Chromatograph (IC) – SYKAM ; Direct mercury analyzer ; Luminometer ;
ZETA -NANOSIZER ; Photochemiluminometer ; UV Irradiation – Bio-Sun ;
Freeze Dryer ; Luzchem Photore actor ; Quantachrome NOVA 2200e ;
Spectrometer HR2000+ ; Spectrometer USB2000+ ; Force Tensiometer Sigma
702 ; Small Equipments ; High Pressure Homogenizer APV 2000 Lab ; High –
shear Homogenizer PRO250 , Franz diffusion cells ; Profilometer https://erris.gov.ro/C
PMTE –UPB

ICECHIM (P1)
Research
Infrastructure for
Circular Agro –
Bioeconomy -Agri-
Flux SmartLab High Resolution X -ray Dif ractometer (HR -XRD) with Ultra -Small -angle
X-ray scattering (U -SAXS) from Rigaku; Transmission electron microscope
(TEM) Tecnai G2 F20 TWIN (FEI) with simultaneous STEM and EDX modules (http://erris.go v.ro/
Circular –
Bioeconomy
Research Centre for
Producing, Conditioning and
Characterization of
Advanced Materials High pressure liquid chromatographer (HPLC) 1200 Series coupled with refractive
index (RID) from Agilent Technologies ; Jenway 3540 pH -metre -Conductometer;
Infrared Spectrometer (FTIR) Thermo Scientific equipped with an ATR unit (with
2 crystals Ge and Zn -Se) and a unit for liquid samples; NMR Spectrometer Oxford
Instruments –Pulsar H&F&C for liquid samples (with the possibility for 2D
mapping) ; UV -visEVOLUTION 260 BIO UV -VIS Spectrophotometer; Autolab
Potentiostat/Galvanostat from Metrohm; (http://erris.gov.ro/
advanced –
materials )
Laboratory for Environmental scanning electron microscope (SEM) Quanta 200 (magnifications (http://erris.gov.ro/123456789101112131415161718192021222324
1 A.1.1 CI
2 A.1.2 CI
3 A.1.3 CI
4 A.1.4 CI
5 A.1.5 CF
6 A.1.6 CI
7 A.1.7 CI
9 A.2.1 CI
10 A.2.2 CI
11 A.2.3 CI
12 A.2.4 CI
13 A.2.5 CI
14 A.2.6 CI
15 A.2.7 CI
16 A.2.8 CI
18 A.3.1 DE
19 A.3.2 DE
20 A.3.3 DE
21 A.3.4 DE
A.3.6 DTASK 3
23A.3.5 DE22SCHEDULE (M1-M24)
TASK 1
A.1.8 8
A.2.917TASK 2D
DTASKS/ ACTIVITY/TYPE
OF ACTIVITY Nr. crt2020 2021 2022CO P1 P2

12
PN-III-CERC -CO-PED -2-2019 Physico -Chemical
Characterization,
Analysis and Testing
of Micro – and
Nanostructured
Hybrid Materials of over 100000x) for polymers, inorganic, hybrid and biological samples; Infrared
Spectrometer (FTIR) Tensor 37 from Bruke r; Dynamic light scattering Instrument
Zetasizer Nano series (DLS). Heterogeneous_Sy
stems )
PLANTAVOREL S.A ( P2)
The Research and
Processing Center
for Medicinal Plants
PLAN TAVOREL
S.A. 1Chopper grinder ROSTOK ; Laboratory mill Kinematica Microtron MB550;
Electric water baths – Precisterm, Univeba, Raypa BAD -2, GFL 1042; Ultrasonic
bath isolab; Microwave extraction system Ethos X; Randall extraction system;
Sepacore Easy Pu rification System; Distillators – Simax, GFL; Binder stove with
natural convection ED 53; Rotary evaporator – Laborota 4000 Efficient; Analytical
balances – Precisa, Mettler Toledo; Technical balance – Mettler Toledo;
Thermobalance Sartorius, Kern; Centri fuges – Rotofix, Hettich ; Thin layer
chromatography system (HPTLC) – Camag Linomat IV, Scanner CAmag TLC 3,
Wincats Planar Chromatography Manager; Spectrophotometer FT -IR Varian
640; Spectrophotometer UV/VIS: Cary 50, UV/VIS GBC Cintra; Magnetic stirrer
with heating VELP -ARE; pH -meter Seven Easy, Inolab Multy 9310; Autoclave
MLS -3870; Binder incubator – BD 115; Colony counter Scienceware; Laminar
flow hood, safety class II ABS 1000. https://erris.gov.ro/
The-Research -and-
Processing –1

• Structure of research teams and justification o f salary expences
First name and
last name Task in the project according to specialization and expertise PMs Costs
lei
UPB (CO)
Liane Raluca Stan
(RS) Prof., PhD, Project Management , Specialist in Oleogel/BigelSynthesis,
Veget able oil and natural extracts characterization, data
interpretation/processing and dissemination activities, 1.00 33600
Ioana Lacatusu , (IL) Assoc Prof., PhD, Key person Lipid based delivery systems, In vitro
controled release tests; efficiency analysis (UV -VIS, HPLC); Data
processing and Dissemination 0.25 8400
Nicoleta Badea
(NB) Assoc Prof., PhD, Key person Lipid based delivery systems, in vitro
controled release tests; in vitro antioxidant activity; efficiency analysis(UV –
VIS, HPLC); Data processing and Dissemination 0.25 8400
Brindusa Balanuca (BB) Lecturer, PhD, specialist in characterization of vegetable oils and TGA,
DSC, FT -IR, UV -Vis analyses, Data processing and Dissemination 1.00 25200
Cristina Ott (CO) Lecturer, PhD. specialist in oleogel/ bigel synthesis and characterization
Data processing and Dissemination 1.00 25200
Andrada Serafim
(AS) Researcher, PhD. specialist in rheological characterization of the new
developed formulations, Data processing 0.38 9600
Emilian Ghibu (EG) PhD stude nt, synthesis and characterization of developed oleogels/bigels 0.79 13200
Elena Danila (ED) PhD student, specialist in isolation and characterization of natural active
principles, oleogel synthesis 0.64 10800
Alina Morosan (AM) PhD student, specialist i n High Resolution Fourier -Transform Ion –
Cyclotron -Resonance (FT -ICR) Spectrometer manipulation 0.38 6400
TOTAL 5.69 140800
ICECHIM (P1)
Anamaria Zaharia, (AZ) CS I, PhD, Person in charge for P1 , Specialist in Hydrogel/Nanogels
Synthesis, High Pressu re Liquid Chromatography (HPLC), data
interpretation/processing and dissemination activities, 1.5 14250

Andrei Sarbu, (AS) CS I, Key person, PhD, IPR Management , Synthesis specialist 1.5 14250/
Tanta -Verona Iordache ,
(VI) CS I, PhD, Key person , Spec ialist in Polymer Composites Synthesis, UV –
vis Spectroscopy, data interpretation/processing, and dissemination
activities 1.5 14250
Anita Laura Chiriac
(Radu), (AR) CS I, PhD, Key person , Specialist in Composite Hydrogels Preparation, X –
Ray Diffraction ( SAX/USAX, GIXRD), data interpretation and processing 1.25 11875
Raluca Ianchis, (RI) CS I, PhD, Specialist TGA/DSC operator and data processing and
dissemination activities 0.5 4750
Luiza Jecu (LJ) CSI, Specialist specialized in microbial strains for b iodegradation of organic
contaminants 1 10310
Melania Liliana Arsene CSI, PhD, Specialist in biotechnology, enzymology, (bio)sensors, 1 6566

13
PN-III-CERC -CO-PED -2-2019 (MA) (bio)materials.
Monica -Mirela Duldner ,
(MD) CS II, Eng, Specialist on Organic synthesis development and d issemination
activities 0.5 3800
Ana Maria Gurban ,
(AG) CSI, PhD, Specialist in biotechnology, applied microbiology, biochemistry;
bioproducts obtainment, microbiological experiments. 0.5 5503
Teodor Sandu, (TS) CS II, PhD, Post -doc, Specialist FT -IR on data processing and
dissemination activities 1.25 9500
Ana-Mihaela Gavrila
(MG) CS III, PhD, Post -doc, Specialist HPLC and UV -vis on data processing and
dissemination activities 1.25 8125
Iuliana Caras
(IC) CS III, PhD, Specialist in Immune and ce ll-based Studies, data interpreta –
tion/processing, and dissemination activities 0.5 3250
Iuliana Răut
(IR) CS III, PhD, Specialist IN in isolation, screening, identification and
characterization of microorganisms, maintenance of microbial collection 0.5 4984
Călin Mariana
(CM) CS III, PhD, Specialist in in isolation, screening, identificatio n and
characterization of microorganisms, maintenance of microbial collection 0.5 3777
Steluta Apostol
(SA) CS III, Process Engineer on technology development 0.5 3250
Bogdan Trica
(BT) CS, Ph.D. Student, Specialist on Transmission Electron Microscopy and
Tomography (S/TEM) and data interpretation 0.5 2250
Alina Elena Coman (EC) CS, Ph.D. Student, Assistance in the synthesis of the new microparticles of
hydrogelcomposites and dissemination 1 4500
Elena -Bianca Stoica (BS) CS, Ph.D. Student, NMR Spect roscopy Operator 1 4500
Razvan Edward Botez
(RB) ACS, MSc, , Synthesis of microparticles of composite hydrogels 1 3500
Crina Thea Cojocaru
(CC) ACS, MSc, Preparation bigel systems 1 3500
Ana Lorena Ciurlica
(LC) ACS, MSc, FT -IR Spectroscopy Operator 1 3500
Andeea Miron
(AM) ACS, MSc, BET Porosity Operator 1 3500
Marinela Victoria
Dumitru (MD) ACS, MSc, UV -vis Spectroscopy Operator 1 3500
Antoaneta Iordachescu
(AI) Subeng, Process Engineer on technology development 0.5 1750
Marioara Berbec , (MB) Technician, Responsible with the consumables 0.6 1750
TOTAL 16.75 150690
Plantavorel SA (P2)
Țebrencu Carmen Elena,
(TCE) CS I, Person in Charge for P2 extracts , development of original, modern
and environmental friendly technologies , data interp retation/processing and
dissemination 15.36 38400
Ionescu Elena
(IE), CS I, Key person, PhD, Specialist in studies on vegetable raw materials
research and processing, screening, identification and characterization of
extracts , data interpretation/proces sing and dissemination 1.2 900
Ciuperc ặ Oana Teodora,
(COT) CS, PhD student , Key person , Specialist in phytochemical studies on
medicinal and aromatic plants , investigation of antioxidant activity, UV-VIS
and FT -IR Spectrometry, data interpretation/processing and dissemination 14.40 28080
Chiriac Maria, (CM) CS III, Specialist in qualitative and quantitative analyses of active
principles in aromatic and medicinal plants by UV/VIS spectrophotometry
and HPTLC densitometry methods , data interpretation and processing 7.20 14400
Pặduraru Catrinel
Florentina , (PCF) CS, PhD , Specialist in extraction techniques in the solid -liquid system,
studies on conditioning techniques, data interpretation and processing 0.90 1958
Bașag Geanina Elena,
(BGE) CS, Bioeng., Specialist in biotechnology, extraction technologies of
bioactive compounds , technology development 1.20 2520
Popovici Maria
(PM) CS, Eng., Specialist in processing and conditioning of extracts from
aromatic and medicinal plants 0.72 1055
Cioclu Lucia, (CL) CS, Eng, Specialist on pr eparation of raw materials for extraction process 0.6 672
Chilat Iulia, (CI) Eng., Specialist in qualitative and quantitative analyses of phytocomplexes
by HPTLC , data interpretation and processing 1.40 1890
Scripcaru Andra Elena, Biologist,Specia list in microbiological analysis, data interpretation and 0.6 766

14
PN-III-CERC -CO-PED -2-2019 (SAE) processing
Iacob Elena, (IE) Subeng., ACS, development of new methods of characterization of
phytocompounds using HPTLC , data interpretation and processing 1.40 2240
Munteanu Mărioara
(MM ) Laboratory Technician, responsible with the laboratory consumables 2.40 2520
Bobu Elena (BE) Laboratory Technician, physico -chemical analyzes, preparation of the
reagents, reference substances solutions. 4.20 4410
Dumitrache Ana Mihaela
(DAM) Laborator y Technician, performing of UV -VIS spectrophotometric analyzes
respecting the methods established by researchers 0.6 630
Damian Ecaterina, (DE) Laboratory Technician, performing of microbiological analyzes respecting
the methods established by researcher s 1.40 1610
Cămărașu Aspazia (CA) Laboratory Technician, preparation of chromatographic reagents respecting
the procedure established by researchers 0.6 630
Dediț ặ Mirela (DM) Laboratory Technician, preparation of chromatographic reference
substances solutions resp ecting the procedure established by researchers 1.52 2566
Jbanca Cornelia
(JC) Laboratory Technician, preparation of raw materials using laboratory
equipments respecting the technology established by researchers 0.60 624
Patac ặ Ana (PA) Laboratory Techni cian, preparation of raw materials using laboratory
equipments respecting the technology established by researchers 0.60 630
TOTAL 56.90 106500

Risks associated with the project
Risks Level
risks Back -up solutions
The selected organogelators produce w eak
gels from NSO and ESO Medium Mixture of gelators and surfactants will be tested
Loss of active compounds at FVoe
encapsulation during gelation Medium Selection of gelators and/or surfactant with lower temperature
requirements
Difficulty in selecting reliabe markers for
encapsulation efficiency and release studies
from CMpc Low Use of the performant Spectrometer, S olariX XR 15T, Bruker
Daltonics , equipped with ESI, APCI ionisation and infusion direct
sample introduction, GC, HPLC, MALDI imaging system s
Removal of the embeded Ag microparticle
from HC-Ag during work -up Medium Bigel synthesis followed by Ag grafting or selection of
another monomer for HC which do not require opurication
The biological activity of the bigels loaded
with natural principl es is unsatisfactory Association of natural principles with a synthetic drug,
favorized by the dual nature of the vehicle
Characterization equipment’s failure Low Fault remediation will be t aken, or the use of research
collaboration alternative with oth er entities that possess similar
equipment
Dissemination channels not appropriate Low Discussion of all the partners and redesigning the
dissemination strategy
Reallocation the initially plannedmounts
from one year to another, by UEFISCDI,
could create d iscontinuities High The work plan will be reconsidered by application of crisis
management in order to achieve the key points of the project

Project Budget :

Justification of total cost for each line of the budget
CO-UPB : Logistics – 30500 lei ( consumables 27500 lei, audit expenses 3000 lei) -vegetable oils, NSO and EPO
~ 500 lei/ Kg, organogelators and surfactants (beeswax, Span 60, Tween 60, Glycerilmonostearat, 12-Allocated budget / costs (Lei)
Personal costs Logistics Travel Indirect costs Total
UPB (CO) Public budget 140800 30500 13300 45400 230000
ICECHIM ( P1) Public budget 150690 16610 9000 43700 220000
PLANTAVOREL
(P2) Public budget 106500 13500 0 30000 15000
Own
contribution 28145 3873 7550 9892 49460
Total 426135 64809 29850 128992 649460

15
PN-III-CERC -CO-PED -2-2019 hydroxystearic acid, lecithin Hydroxypropilcellulose ), FVeo, HPLC solvents, Standards for chromatography, He
gas, Ar gas, liquid nitrogen, plastic and glass ware, consumables for therma l analyses, DSC, usual solvents ,
maintanence of infrastructure, Travel :13300 lei : Partner meeting s and 3 conferences/national and international
scientific events i.e.participation fees, accommodation, diurnal fees and transport (airplane, train, bus and
internal transport ), Overhead 45400 lei were calculated as 25% relative to direct costs meaning per sonnel,
logistics and travel without equipments and services.
P1-ICECHIM ; Logistic s 16310 Lei (Consumables: 8310 Lei, Open Access Fee 8000 Lei): Precursors for
macromonomers (PEG, methacryloyl chloride and solvents1284 lei) and other precursors for micropa rticle of
hydrogel composites –silver microparticles ( 1526 lei ), consumables for the antifungal susceptibility test of the
antimycotic in agreement with the EUCAST recommendations (4060lei) plastic and glass ware (480 lei), Liquid/
Gas Nitrogen (960 lei) .Travel (9000 Lei): Costs for 2 conferences/national and international scientific events
i.e.participation fees, accommodation, diurnal fees and transport (airplane, train, bus and internal transport) were
included in this category. Overheads (44000 Lei) were calculated as 25% relative to direct costs meaning
personnel, logistics and travel without equipments and services.
P2- Plantavorel – Logistics: (consumables – 10266 lei – solvents, laboratory ware, standards, reagents)
Overheads (30000 Lei )

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