Effect of divalent cations on pore formation and degradation of poly(D,L-lactide-co-glycolide)

Poly(D,L-lactide-co-glycolide) (PLG) is probably the biodegradable polymer most often used for polymeric controlled-release formulations. Different salts have been shown to affect the swelling and degradation of PLG, which, in turn, affect the release of encapsulated drugs. In this investigation the effect of divalent cations was especially investigated. Films of PLG were incubated in phosphate buffer saline (PBS), a buffer containing salts similar to plasma, Hepes buffer, and Hepes buffer with ZnCl2, CaCl2, MgCl2, or Na2CO3 added. Pore formation at the surface and inside the film was analyzed by scanning electron microscopy. The samples were also analyzed gravimetrically at predetermined intervals to determine the mass loss, and for some samples the pH within the PLG films was determined by confocal microscopy. Pores were formed faster in the presence of all divalent cations, and the results indicated a greater degradation rate in the presence of Zn2+. The catalyzing effect of the divalent cations on degradation was attributed to their ability to act as Lewis acids. Pores were formed more slowly in PBS than in a buffer containing salts similar to plasma, which should be considered when choosing the in vitro release medium.