INTRODUCTION Dexamethasone is a poorly soluble and crystalline corticoid that is often used for the treatment of diabetic macular edema administered as an implant (Posurdex, Oculex Pharmaceuticals).1 Micelle systems are known to solubilise poorly soluble hydrophobic drugs in an aqueous solution, thus increasing their bioavailability in the body.2The goal of this work is to demonstrate the encapsulation of dexamethasone from biodegradable polymer micelles, composed of a triblock copolymer of poly(polycaprolactone)-b-poly(2-ethyl-2-oxazoline)-b-polymer(polycaprolactone) (PCL-PEtOz-PCL) for intravitreal injection. The potential of PCL-PEtOz-PCL micelles as carriers for dexamethasone was evaluated by estimating the loading efficiency. A the end, to ensure that the materials studied are appropriate for biomedical application, the cell cytotoxicity of the micelle was evaluated using macrophages cell RAW 264.7.EXPERIMENTAL METHODS The triblock copolymers were synthesized in a three step reaction process. Firstly, PEtOz with di-acrylate end groups was prepared by cationic ring opening polymerization; acrylate end group was introduced by end capping of acrylic acid after polymerization. Secondly, mono thionic acid PCL block were synthesized by ring opening polymerization and termination group was modified with glutaric thioanhydride. The triblock copolymers were then prepared by thioic-ene addition reaction at RT.3 This block copolymer was self-assembled into micelles in an aqueous solution using nano-precipitation method.4 The block copolymer were characterized by 1H NMR spectra and GPC. The loading efficiency and content of dexamethasone for micelles was determined by HPLC.RESULTS AND DISCUSSION Table 1 show the characteristics of the PLA-PEtOz-PLA triblock copolymer studied. Dexamethasone loading into PCL-PEtOz-PCL micelles occurred simultaneously with self-assembly of block copolymers into micelles. Polymer micelles of PCL-PEtOz-PCL block copolymer exhibited a remarkable capability for carrying dexamethasone. Up to 14.86 wt% of drug was successfully loaded into nanoparticles. No precipitated drug crystals were observed and a clear aqueous solution was obtained, and the particle sizes were in a range of 86 nm with a narrow size distribution (PDI = 0.12). In addition, the biocompatibility of the micelles was investigated macrophages cell RAW 264.7. Study of the MTT assays showed that PCL-PEtOz-PCL micelles were quite biocompatible because they showed minimal influence on cell viability in a concentration of up to 1 mg mL-1.CONCLUSION In conclusion, we have successfully synthesized a block copolymer micelle system that are show good biocompatibility as drug delivery vehicles. Dexamethasone was successfully loaded into PCL-PEtOz-PCL micelles up to 14.86wt%. These results suggest that PCL-PEtOz-PCL micelles can be regarded as promising carriers for dexamethasone.REFERENCES 1. C. G�mez-Gaete et al., Int. J. Pharm. 331 (2007), 153-1592. R. Luxenhofer et al., Biomaterals, 2010 (31), 4972-49793.a) WO2007/028612 (b) WO2010/ 070132 A.A. Dias et al.4.US201110223206A1, J. Lebouille et al.ACKNOWLEDGMENTS The authors acknowledge European Union (7th Research Framework Programme: PANOPTES/246180) for providing financial support to this project.

Biodegradable polyoxazoline based nanoparticles as a drug carrier

248th National Meeting (2014)

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