Abstract
Poly (lactide-co-glycolide) (PLGA), one of the FDA approved polymer, has widely applied in the drug delivery system for many years. PLGA is a non-toxicity, good biocompatibility and biodegradability polymer. The PLGA polymer biodegrades into lactic and glycolic acids. Lactic acid enters the tricarboxylic acid cycle and is metabolized and subsequently eliminated from the body as carbon dioxide and water. Our group synthesizes five platinum complexes, including sulfoplatin and its derivative, PtCl(sulindac-S=O)[η2-C5H4SN(O)], PtCl(sulfinpyrazone)[η2- C5H4SN(O)], Pt(1-(2-tetrahydrofuryl)-5-fluorouracil-3-yl)(DMSO)[η2-C5H4S- N(O)] and [Κ-(5-fluorouracil-3-yl)]Pt2(DMSO)2[η2-C5H4SN(O)]2. In this study we applied three kinds of molecular weight size polymer and nanoprecipitation method to prepare PLGA nanoparticles loaded with platinum complexes. The yield, drug content, entrapment efficiency determined by UV-Vis spectrophotometer. The yield were 1.54%–12.3%; drug content were 0.915%–14.6% and entrapment efficiency were 0.337%–23.0%. The effect of different size molecular weight polymer and platinum complexes on entrapment efficiency was investigated. The larger molecular weight polymer and more lipophilic platinum complexes has the better entrapment efficiency. The physical property of platinum complexes has the affect on drug content. The nanoparticle recovery step however needs further mprovements, since bridges between particles which cause focculation could be observed. It was found that a molecular weight of 49.67-69.58KD and loaded with platinum complex 2 PLGA nanoparticles has the yield 5.65%, drug content 14.6% and entrapment efficiency 23.0%. Approaches investigated for the enhancement of drug entrapment efficiency included the infuence of initial platinum complexes content and organic to aqueous phase volume ratio. Increase in platinum complexes content resulted in increase in drug content, but no effect on yield and entrapment efficiency. It was found that a molecular weight of 49.67-69.58KD and loaded with platinum complex 3 PLGA nanoparticles, when platinum complexes content was 10.0% has the yield 17.6%, drug content 21.5% and entrapment efficiency 37.6%. Increase in organic to aqueous phase volume ratio resulted in increase in drug content but decrease in yield and entrapment effciency. It was found that a molecular weight of 49.67-69.58KD and loaded with platinum complex 2 PLGA nanoparticles, when organic to aqueous phase volume ratio was 0.05 has the yield 17.6%, drug content 21.5% and entrapment efficiency 37.6%. The formulation variable could be exploited in order to enhance the incorporation of platinum complexes into PLGA nanoparticles. Hence the developed platinum complexes loaded PLGA is suitable for drug delivery in treatment of cancer.