Supercritical emulsion extraction fabricated PLA/PLGA micro/nano carriers for growth factor delivery. Release profiles and cytotoxicity

Controlled delivery of human growth factors is still a challenge in tissue engineering protocols, and poly-lactic acid and poly-lactic-co-glycolic acid carriers have been recently proposed for this purpose. Here, the microencapsulation of two human growth factors, namely Growth Differentiation Factor −5 (hGDF-5) and Transforming Growth Factor β1 (hTGF-β1) was tested, by processing different emulsions with Supercritical Emulsion Extraction (SEE) technology. Polymer molecular weight, co-polymer ratio and surfactant amount in aqueous phases as well as phases mixing rate were varied to fabricate carriers with suitable size and loadings. Carriers with different mean sizes from 0.4 ± 0.09 μm up to 3 ± 0.9 μm were obtained by SEE technology when processing emulsions with different formulations; carriers were loaded with 3 μg/g and 7 μg/g for hGDF-5 and hTGF-β1 with controlled growth factor release over 25 days. Carriers displayed extremely low cytotoxicity when evaluated in Chinese Hamster Ovary cells (CHO-K1). Further, they also exhibited reduced cytotoxicity with respect to carriers obtained by conventional evaporation techniques, and low reactivity on human peripheral blood mononuclear cells (hPBMCs), suggesting their safety and potential use in tissue engineering protocols.