Biodegradable graft polyesters based on copolymer of lactic acid and glycolic acids grafted onto poly(vinyl alcohol) for oral vaccine delivery

Abstract

Small nanospheres prepared by spontaneous polymer - protein self-assembling are an attractive concept for the preparation of nanoscale drug delivery systems, since the use of solvents and surfactants can be avoided. For this purpose, polyesters were prepared by grafting poly(lactic acid-co-glycolic acid) (PLGA) chains onto poly(vinyl alcohol) (PVAL) or the negatively charged sulfobutylated poly(vinyl alcohol), P(SBVE). Adjustment of PLGA chain lengths by feed composition allowed to modify polymer properties, such as molecular weight and solubility. While polyesters with a chain length of 5-10 lactic or glycolic acid units showed on average good solubility in acetone, further chain length reduction yielded water-soluble polymers. In aqueous solution, a lower critical solution temperature was observed. Spontaneous formation of colloidal polymer - protein conjugates with a variety of proteins, such as tetanus toxoid, recombinant human nerve growth factor and insulin was investigated. Sizes ranging from ca. 100 nm to several μm and protein loading of up to 200 % could be attained by changing factors, such as pH, temperature and polymer type. Complex formation was fully reversible. Bioadhesion in a Caco-2 cell culture model and measurable antibody titers in mice using tetanus toxoid - polymer conjugates suggest that these polymers could be of interest for protein delivery and mucosal vaccination.