pH-sensitive hydrogels based on poly(methacrylic acid), casein and liposomes for targeted delivery of poorly water-soluble active substances

Abstract

Polymeric carriers for targeted delivery of poorly water-soluble active substances (PWSAS) are facing two challenges. First, encapsulation of PWSAS depends on structure of the carrier. Second limitation is caused by the phenomenon of burst drug release. Despite the fact that the fast release of drug in a burst stage is utilized in certain drug administration strategies, the negative effects brought about by burst can be pharmacologically dangerous and economically inefficient. This study presents a novel strategy for encapsulation and targeted delivery of PWSAS - caffeine without the possibility of burst effect. Hydrophilic carrier based on poly(methacylic acid) was modified by amphiphilic substances - casein and centrifuged liposomes to ensure caffeine encapsulation. The caffeine was encapsulated in liposomes which further were incorporated into the carrier networks during the synthesis of the carriers. The release kinetic of caffeine was analyzed with respect to morphology of the carriers and interactions that could be established between the components of the carrier. The swelling of carriers and release of caffeine were further investigated depending on the neutralization degree of methacrylic acid in two media with different pH simulating the path of the carrier through the upper and lower human gastrointestinal tract. Synthesized carriers showed significant potential for encapsulation and targeted delivery of PWSAS.

Kod razvoja polimernih nosača za ciljano otpuštanje slabo vodorastvornih aktivnih supstanci (SVAS) postoje dva ograničenja. Prvo, inkapsulacija SVAS zavisi od strukture nosača. Drugo ograničenje je vezano za naglo oslobađanje leka. Uprkos činjenici da je naglo oslobađanje leka, tzv. burst efekat poželjno kod nekih sistema, negativni efekti naglog oslobađanja leka u većini slučajeva mogu biti farmakološki opasni i ekonomski neefikasni. U ovom radu je prikazana nova strategija za inkapsulaciju i ciljano otpuštanje SVAS – kofeina bez burst efekta. Hidrofilni nosač na bazi poli(metakrilne kiseline) je modifikovan amfifilnim supstancama – kazeinom i centrifugiranim lipozomima kako bi se postigla inkapsulacija kofeina. Kofein je inkapsuliran u lipozome koji su zatim inkorporirani u mrežu nosača tokom sinteze nosača. Analiziran je uticaj morfologije nosača i interakcija koje su se uspostavile između njegovih komponenti na kinetiku otpuštanja kofeina. Zatim je analiziran uticaj stepen neutralizacije metakrilne kiseline na bubrenje nosača i otpuštanje kofeina u dve sredine različitih pH vrednosti koje su simulirale pH sredinu u gastrointestinalnom traktu čoveka. Pokazano je da sintetisani nosači imaju veliki potencijal za inkapsulaciju i ciljano otpuštanje SVAS