One-step synthesis of poly(lactic-co-glycolic acid)-g-poly-1-vinylpyrrolidin-2-one copolymers

In this work we present a one-pot synthetic process leading to poly(lactide-co-glycolide)-g-poly(1-vinyl-2-pyrrolidone) (PLGA-g-PVP) copolymers consisting of high molecular weight PLGA carrying oligomeric PVP side chains. PLGA is a lipophilic biodegradable polymer, whereas PVP is hydrophilic, biocompatible and bioeliminable for molecular mass < 40,000. Both polymers have been approved for human use by the US Food and Drug Administration, therefore PLGA-g-PVP copolymers are eligible for medical applications. The water-soluble PVP portion imparts amphiphilic properties to the otherwise hydrophobic PLGA, thus modifying its behaviour in aqueous systems. The title copolymers were prepared by bulk radical polymerization of 1-vinyl-2-pyrrolidone in the presence of PLGA 50:50 acting as polymeric chain transfer agent, and characterized by 1H-NMR, FT-IR, DSC, TGA.They were also saponified giving PLGA degradation products and PVP with molecular mass in the range 2.7K-28K, lower than the renal filtration threshold. The MALDI-TOF spectra of the PVP obtained after PLGA-g-PVP saponification were consistent with low molecular weight PVP chains bearing at one end a hydrogen atom and at the other end monomeric, dimeric or, to a minor extent, trimeric residues of lactic- and glycolic acid or their combinations. These data unambiguously confirmed that the PVP chains had been covalently grafted onto the PLGA backbone. The orthogonal solvent pair ethyl-acetate/methanol was used to fractionate PLGA-g-PVP. Preliminarily, the effectiveness of this pair was tested on PLGA/PVP intimate blends obtained by co-precipitation of PLGA/PVP co-solutions. In this case, the complete separation of the two components was achieved. However, in the case of PLGA-g-PVP only PLGA- and PVP-rich fractions with widely different compositions, but not pure homopolymers could be separated. All un-fractionated PLGA-g-PVP samples and their fractions gave stable nanodispersions in water by the solvent evaporation technique, irrespective of the PVP content. Similar results were obtained with PLGA/PLGA-g-PVP blends, but not with PLGA/PVP blends, which gave unstable nanodispersions in water. These data suggest that the PLGA-g-PVP copolymers have a potential as components of bioeliminable and nanodispersed drug delivery systems.