Preparation of drug delivery biodegradable PLGA nanocomposites and foams by supercritical CO2 expanded ring opening polymerization and by rapid expansion from CHCIF2 supercritical solutions

Abstract

ABSTRACTThe synthesis of poly(lactic-co-glycolic acid) (PLGA) by the ring opening copolymerization of D, L-lactide and glycolide was performed at 110 °C to 130 °C using Sn(Oct)2 as catalyst, 1, 10-decanediol as initiator in a supercritical sc-CO2 expanded medium at pressures of up to 3, 500 psi. Due to the limited monomer solubility in sc-CO2 at low temperatures (70 °C), only Mn = 2, 500 is typically obtained. However, molecular weight increases with both temperature and sc-CO2 pressure. Thus, Mn = 13, 000 (PDI = 1.28) was obtained at 110 °C - 130 °C even in the absence of fluorinated surfactants. Biodegradable drug delivery nanocomposites based on dexamethasone and poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) were prepared by the rapid expansion of the corresponding supercritical CHClF2 solutions (110 °C, 200-300 bar) in air (RESS) and in toluene (RESOLV). The RESS process leads to a broad particle size distribution (100-500 nm) while the RESOLV generates a narrower distribution centered around 100 nm and is accompanied by the formation of a few large particles, most likely due to aggregation.