Star-Block Biodegradable polymers for Drug Delivery

Abstract

“Self-assembly of Linear block copolymers” rely heavily on critical micelle concentration for “loading and delivery of drugs”. In my MS project we wanted to tackle the problem and for that, we have chosen a unimolecular micelle approach. The choice of initiator was important as it decides how many arms the polymer will have. We have chosen dipentaerythritol as the 6-arm initiator and for the backbone of the polymer, we have chosen caprolactone and substituted caprolactone which play the role of hydrophobic core and hydrophilic outer layer respectively and can be enzymatically degraded by the lysosomal esterase enzyme in the cells. Monomer and polymers were “characterized using 1H NMR and the molecular weights of the polymers were determined by gel permeation chromatography (GPC)” using CHCl3 solvent. “Differential scanning calorimetry” was used to study the semi-crystalline and amorphous nature of polymers. Post polymerization reactions were done to deprotect the Star- PCL60-b-BPCL60 polymer and then further introduced surface charge by converting -COOH to -COONa group. To determine the unimolecular nature of the polymers “Pyrene was used as a probe” and the change in I1/I3 was recorded against log (concentration of polymer). I1/I3 was independent of the concentration which confirms the unimolecular nature of the “star block copolymers” formed. The size of the “star block copolymer” nano carriers were measured by DLS and for Star- PCL60-b-COOH-PCL60, Star- PCL60-b-COONa-PCL60 and Star- PCL60-b-COONa-PCL60 with loaded curcumin drug were found to be 33 d. nm, 38 d. nm, 79 d. nm respectively. “Drug loading content (DLC) and efficiency (DLE)” were recorded using Curcumin as a anti-bacterial and anti-cancer drug and Topotecan hydrochloride as a anti-cancer drug. Curcumin was loaded in COO-Na+-deprotected star-BPCL polymer with DLC of 4% and DLE of 40%. For topotecan hydrochloride no loading was seen. To measure the cytotoxicity of the “nascent and drug loaded polymers” MTT assay was conducted. Nascent polymer was found to be non-toxic upto 1µg/mL and drug loaded polymer achieved a killing of 40% at 1µg/mL. Rate of biodegradability was studied by performing release kinetics studies and was found to be proportional with time till 18 h after which saturation happened and complete release was achieved in 24 h.