Functionalized Three-Arm Poly(??-Caprolactone) Maleic Acid Microspheres for Controlled Protein Release

Abstract

IntroductionThe objective of this work was to fabricate a novel class of protein carriers from double-bond-functionalized multiarm poly(ε-caprolactone) maleic acid (PGCLM) microspheres and to examine protein sustained-release profiles in vitro over a period of a few months.MethodsThe double-emulsion technique was used to formulate terminal functionalized three-arm PGCLM microspheres having three different types of functional groups (-OH, -COOH, and -C = C-), and one of the functional groups (>C = C< bonds) was used to formulate surface-crosslinked microspheres (NPGCLM). Ovalbumin (OVA) was used as a model protein for examining its release profiles from PGCLM and NPGCLM microspheres in 0.1M phosphate-buffered saline (PBS) at 37°C. These microspheres were also characterized in terms of their morphology, size distribution, and stability.ResultsThe mean size of fabricated microspheres ranged from 21.9µm to 51.1µm. An OVA protein was successfully encapsulated into these biodegradable PGCLM microspheres with loading efficiency ranging from 34.2% to 46% (w/w), depending on the ratio of PGCLM to polyvinyl alcohol (PVA) stabilizer. Depending on the polymer to PVA stabilizer ratio, the cumulative OVA release % (w/w) in 0.1M PBS at 37°C ranged from 30% to 40% within 50 days. We further demonstrated the availability of the functional >C = C< bonds on the surface of PGCLM microspheres, which we expect could be used for either covalent binding of bioactive agents or imparting different chemical characteristics onto the surface of the microspheres for broadening of their applications.Discussion/ConclusionA method for the preparation of biodegradable microspheres from water/oil emulsion of multiarm and functionalized poly(ε-caprolactone) [PGCL, PGCLM, and NPGCLM] was reported as a potential means of developing injectable therapeutic formulations for drugs. The most unique aspect of these biodegradable microspheres is the availability of two functional groups (>C = C< bonds and -COOH pendant group) on the microsphere surface for potential additional chemical or/and biochemical modifications, such as the formation of crosslinked network surface structure. The incorporation of terminal hydrophilic functional maleic acid into hydrophobic three-arm PGCL chains significantly improved the loading efficiency of OVA and its release profiles. These functionalized biodegradable microspheres may provide a good alternative to linear aliphatic polyester-based drug delivery systems and resulted in development of a long-acting, injectable drug carrier for sustained drug release over a period of few months.