Biodegradable comb polyesters containing polyelectrolyte backbones facilitate the preparation of nanoparticles with defined surface structure and bioadhesive properties

A major challenge in oral peptide and protein delivery remains the search for suitable carrier systems. Therefore, a new concept was investigated combining a modified three-dimensional architecture, increased hydrophilicity of poly(lactic-co-glycolic acid) (PLGA) and charged groups in a single polymer. Biodegradable comb PLGA were synthesized by grafting short PLGA chains onto different poly(vinyl alcohol) (PVA) based backbone polyols, poly(2-sulfobutyl-vinyl alcohol) and poly(diethylaminoethyl-vinyl alcohol). The polyelectrolyte backbones were obtained by etherification of PVA with charge-containing pendent groups. The comb polymer structure could be confirmed by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, elemental analysis and measurement of intrinsic viscosity. Nanoparticles (NP), as potential mucosal carriers systems, were prepared by controlled precipitation and investigated as a function of polymer composition. The amphiphilic character and the three-dimensional architecture of the novel polyesters allowed the preparation of small nanoparticles even without the use of surfactants. Surface NMR, surface charge and hydrophobicity determination indicate a core–corona-like NP structure, especially in the case of negatively charged polyesters. A structural model is proposed for the NP with an inner polyester core and an outer charged-groups-containing surface, depending on polymer composition and backbone charge density. The higher the polymer backbone charge density, the more pronounced its influence on the nanoparticle surface properties. The possibility of preparing NP without the use of a surfactant, as well as of designing the NP surface characteristics by polymer backbone charge density and polymer hydrophilic–hydrophobic balance, will be a major advantage in protein adsorption, bioadhesion and organ distribution. This makes these biodegradable polymers promising candidates for colloidal protein and peptide delivery. Copyright © 2003 John Wiley & Sons, Ltd.