Aplicatii ale nanomedicinii in imunomodulare si transplant renal [614704]

Aplicatii ale nanomedicinii in imunomodulare si transplant renal
Introducere
La ora actuala lumea medicala incepe sa cunoasca din ce in ce mai multe aplicatii ale
nanomedicinii. Este si cazul nanoparticulelor utilizate in imunomodulare. Sistemul imun reprezinta
un mecanism complex care protejeaza organismul de structuri straine (non-self). Nanoparticulele
sunt capabile sa interactioneze cu sistemul imun stabilind directia spre imunostimulare sau
imunosupresie. Aceaste interactiuni pot aduce beneficii dar in acelasi timp pot crea situatii
periculoase. De exemplu unele nanoparticule pot avea efecte anti-atumorale in vitro (inhiba
cresterea tumorala) dar aplicate in vivo pot avea efect contrare de stimulare a dezvoltarii tumorale.
De aceea potentialul imunomodulator al nanoparticulelor ar trebui aplicat cu precautie in cadrul
trialurilor clinice datorita posibilelor efecte adverse extrem de grave.
Transplantul renal aspecte generale
Transplantul renal reprezinta o solutie terapeutica in cazul insuficientei renale spre deosebire de
hemodializa care doar substituie functia renala fara sa amelioreze comorbiditatile (in special cele
legate de sistemul cardiovascular). Este din ce in ce mai folosit datorita eficientei crescute, a
costurilor mai mici comparate cu hemodializa cronica sau dializa peritoneala si a reintroducerii
pacientului in viata pe care o avea inainte de stadiul terminal al bolii. Succesul terapeutic depinde
de perfectiunea actului chirurgical pe termen scurt (prin evitarea complicatiilor acute printre care
pe primul loc tromboza) si de monitorizarea postoperatorie de durata ce combina tratamentul
imunosupresor cu diferite terapii ce tin stationare diversele patologii asociate (diabetul zaharat,
boala coronariana, ateroscleroza etc.). De aceea este foarte important ca tratamentul imunosupresor
sa tina cont de interactiunile medicamentoase (prin modificarea nivelelor plasmatice) si sa fie
monitorizat atent pe toata perioada de viabilitate a grefei renale.
Exemple de nanoparticule implicate in imunomodulare
1. Carbon nanotubes
Induc imunosupresie sistemica, (studiata la soareci), includ eliberarea de prostaglandine si
interleukine si alterarea mecanismelor celulelor T.
2. Fullerene
Elimina radicalii liberi, este recunoscut ca un antiinflamator puternic ce actioneaza scaderea
eliminarii de specii reactive de oxigen, a nivelului de histamina si a factorului de necroza tumorala
alfa.
3. Gold Nanoparticles
Studiile arata ca particulele de anumite dimensiuni pot inhiba raspunsul celular indus de
interleukina 1 beta.
4. Silver Nanoparticles
Interactioneaza cu expresia genelor Malt1 si Sema7a asociate cu functionalitatea celulelor implicate
in sistemul imunitar.
5. Magnetic Nanoparticles
Diferente mari in ceea ce priveste efectul intre studiile efectuate in vitro si cele efectuate in vivo.
Doza mari pot induce stresul oxidativ.
6. CeO2 Nanopaticles

Efect dependent de diametrul nanoparticulelor, efect semnificativ antiinflamator.
7. Polymeric Nanoparticles
Efect antiinflamator desi studiile in vivo au aratat ca nu influenteaza imunitatea gazdei.
Medicamente dezvoltate prin intermediul nanomedicinii
Unul din medicamentele utilizate in cadrul terapiei la pacientul transplantat este sirolimus. Acesta
este un compus insolubil in apa, cu puternic efect imunosupresor, al carui aspecte legate de
biodisponibilitate, stabilitate in vivo si transportul catre tinte a fost imbunatatit prin dezvoltarea
formulei orale cu ajutorul tehnologiei Nanocrystal. Acest medicament prezinta o serie de avantaje si
dezavantaje. Proprietatile ce tin de siguranta, eficacitate si biodisponibilitate difera semnificativ
intre forma lichida si forma solida dezvoltata cu ajutorul nanoparticulelor. Fiind incadrat ca un
medicament din clasa imunosupresoarelor, acesta demonstreaza un raport cost-eficienta superior
spre deosebire de alti compusi inruditi cum ar fi tacrolimus sau ciclosporina.
Concluzii
Cu o populatie din ce in ce mai imbatranita la nivel global, este de asteptat ca medicina sa dezvolte
noi solutii pentru a mentine sub control si pentru a trata patologiile corespunzator. Noi aplicatii ale
nanomedicinii sunt testate si introduse in practica medicala in fiecare zi.
Pe de alta parte, trebuie sa incercam sa maximizam beneficiile nanoparticulelor in ceea ce priveste
imunomodularea fiind atenti de asemenea la efectele adverse care pot fi cu raspuns
sistemic.Nanomedicina la acest capitol este inca la inceput dar viitorul suna optimist.
Applications of nanomedicine in immunomodulation and renal transplantation
Introduction
Nowadays the medical world is starting to know more and more applications of
nanomedicine. This is also the case of nanoparticles used in
immunomodulation. The immune system is a complex mechanism that protects
the body from non-self structures. Nanoparticles are able to interact with the
immune system by directing towards immunostimulation or
immunosuppression. These interactions can bring benefits but at the same
time can create dangerous situations. For example, some nanoparticles may
have anti-tumor effects in vitro (inhibit tumor growth) but applied in vivo may
have the opposite effect of stimulating tumor growth. Therefore, the
immunomodulatory potential of nanoparticles should be applied with caution in
clinical trials due to the potentially serious side effects.
Renal transplantation general issues

Renal transplantation is a therapeutic solution for kidney failure in contrast to
hemodialysis that only substitutes renal function without improving
comorbidities (especially those related to the cardiovascular system). It is
increasingly being used due to the increased effectiveness of lower costs
compared to chronic hemodialysis or peritoneal dialysis and to the reinsertion
of the patient to life before the terminal stage of the disease. The therapeutic
success depends on the perfection of short-term surgery (avoiding acute
complications such as thrombosis) and post-operative follow-up combining
immunosuppressant therapy with therapies that keep stable the various
pathologies associated (diabetes, coronary artery disease, atherosclerosis
etc .). Therefore, it is very important that immunosuppressant treatment take
into account drug interactions (by altering plasmatic levels) and be closely
monitored for the entire lifetime of the renal graft.
1. Carbon nanotubes
They induce systemic immunosuppression (studied in mice), including the
release of prostaglandins and interleukins and alteration of T cell mechanisms.
2. Fullerene
Eliminating free radicals, is recognized as a powerful anti-inflammatory that
reduce the reactive oxygen species, histamine level and alpha tumor necrosis
factor.
3. Gold Nanoparticles
Studies show that particles of certain sizes can inhibit cellular response induced
by interleukin 1 beta.
4. Silver Nanoparticles
It interacts with the expression of the Malt1 and Sema7a genes that are
associated with cell function involved in the immune system.
5. Magnetic Nanoparticles
Significant differences in effect between in vitro and in vivo studies. The high
dose can induce oxidative stress.
6. CeO2 Nanopaticles
Significant anti-inflammatory effect dependent on nanoparticle diameter.
7. Polymeric Nanoparticles

Anti-inflammatory effect although in vivo studies have shown that it does not
affect host immunity.
Drugs developed through nanomedicine
One of the drugs used in transplanted patient therapy is sirolimus. This is a
water-insoluble compound with a strong immunosuppressive effect, whose
aspects of bioavailability, in vivo stability and transport to targets has been
improved by developing the oral formula with Nanocrystal technology. This
drug has a number of advantages and disadvantages. The safety, efficacy and
bioavailability properties differ significantly between the liquid form and the
solid form developed with nanoparticles. Being a drug of the
immunosuppressive class, it demonstrates a higher cost-effectiveness ratio
than other related compounds such as tacrolimus or cyclosporine.
Conclusions
With an increasingly aging global population, it is expected that medicine will
develop new solutions to keep it under control and to treat the appropriate
pathologies. New applications of nanomedicine are tested and introduced into
medical practice every day.
On the other hand, we must try to maximize the benefits of nanoparticles in
terms of immunomodulation, also paying attention to the side effects that can
be systemically responsive. Nano-medicine in this chapter is still at the
beginning but the future sounds optimistic.