Preparation of drug delivery biodegradable PLGA nanocomposites and foams by supercritical CO_2 expanded ring opening polymerization and by rapid expansion from CHClF_2 supercritical solutions

摘要

The synthesis of poly(lactic-co-glycolic acid) (PLGA) by the ring opening copolymerization of D,L-lactide and glycolide was performed at 110℃ to 130℃ using Sn(Oct)_2 as catalyst, 1,10-decanediol as initiator in a supercritical sc-CO_2 expanded medium at pressures of up to 3,500 psi. Due to the limited monomer solubility in sc-CO_2 at low temperatures (70℃), only Mn = 2,500 is typically obtained. However, molecular weight increases with both temperature and sc-CO_2 pressure. Thus, Mn = 13,000 (PDI = 1.28) was obtained at 110℃ - 130℃ 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 CHClF_2 solutions (110℃, 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.