Supercritical CO₂ - assisted production of PLA and PLGA foams for controlled thymol release

Amorphous, medical grade poly(d,l-lactic acid) (PLA) and poly(d,l-lactic-co-glycolic acid) (PLGA) were used to develop systems for controlled release of a natural bioactive substance - thymol. Supercritical carbon dioxide (scCO₂) was successfully used both as an impregnation medium for thymol incorporation into the polymer matrix and a foaming agent in a single-step batch process. Impregnation of samples using low to moderate scCO₂ densities (273 kg/m³ and 630 kg/m³) and short processing times (2 h and 4 h) enabled thymol loading of 0.92%-6.62% and formation of microcellular foams upon system depressurization. Thymol effect on structural and thermal properties on foamed samples was proven by FTIR and DSC. The effect of CO₂ under elevated pressure on the neat polymers was analysed by high pressure DSC. Foaming of polymers with lower molecular weight by CO₂ of higher density yielded foams with smaller pores. All tested foams released thymol in a controlled manner in phosphate buffered saline (PBS) at 37 °C within 3 to 6 weeks. Higher loading and lower cell density favoured thymol release rate, while its concentration in PBS for the tested period depended on foam interaction with the medium. Representative PLGA foam sample with the highest thymol loading (6.62%) showed controlled thymol release within 72 h in mediums having pH values from 1.1 to 7.4.