Low melting point and amphiphilic polymer microspheres for therapeutic protein delivery
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Biodegradable microspheres have been extensively studied for controlled and minimally invasive in situ protein delivery. Their small size and thus ready injectability makes this device extremely popular for localized administration, which is particularly advantageous for protein delivery applications. In this study, amphiphilic low melting biodegradable tri-block copolymers of PEG, ε-caprolactone and glycolide monomers were synthesized using bulk ring-opening polymerization (ROP). The design and characterization of this biodegradable copolymer was focused on the formation of microspheres for localized, controlled delivery of the therapeutic chemokine protein SDF-1α. Molecular weight and compositional changes were used to tailor the thermal properties of the copolymers so that the produced materials were solid at room temperature but had minimum crystallinity after hydration at 37 °C. A complete degradation was achieved for the copolymers studied within eight weeks with minor acidic degradation effect on the external and internal microenvironment pH of the microspheres. The copolymers exhibited great ability for microsphere formation with high protein encapsulation efficiency (≥75%) using an electrospraying technique. Prolonged release of SDF-1α was observed with its bioactivity well retained after encapsulation and release, as analysed using cell-based assays.