Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA) to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA) was selected as model compound because of its sensitiveness of γ-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of M(w) and T(g) of the starting PLGA (M(w )(PLGA) = 26.3 ± 1.3 kDa vs. M(w )(g-CA-PLGA) = 22.8 ± 0.7 kDa; T(g)( PLGA) = 47.7 ± 0.8 °C vs. T(g)( g-CA-PLGA) = 47.4 ± 0.2 °C). By using a W(1)/O/W(2) technique, g-CA-PLGA improved the encapsulation efficiency (EE), suggesting that the presence of caffeic residues improved the compatibility between components (EE(PLGA) = 35.0% ± 0.7% vs. EE(g-CA-PLGA) = 95.6% ± 2.7%). Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were −25 mV and −15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of M(w) and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs.