Preparation of Drug Delivery Biodegradable PLGA Nanocomposites and Foams by Supercritical COsub2 Expanded Ring Opening Polymerization and by Rapid Expansion from CHCIF2 Supercritical Solutions

The synthesis of polylactic-co-glycolic acid PLGA by the ring opening copolymerization of D,L-lactide and glycolide was performed at 110 deg C to 130 deg C using SnOct2 as catalyst, 1,10-decanediol as initiator in a supercritical sc-CO2 expanded medium at pressures of up to 2,500 psi. Due to the limited monomer solubility in sc-CO2 at low temperatures 70 deg C, only Mn2,500 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 deg C - 130 deg C even in the absence of fluorinated surfactants. Biodegradable drug delivery nanocomposites based on dexamthasone and polylactic acid PLA and polylactide-co-glycolide PLGA were prepared by the rapid expansion of the corresponding supercritical CHCIF2 solutions 110 deg 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.