Entrapment ability and release profile of corticosteroids from starch-based microparticles

We previously described the synthesis of starch- based microparticles that were shown to be bioactive (when combined with Bioactive Glass 45S5) and noncytotoxic. To further assess their potential for biomedical applications such as controlled release, three corticosteroids with a sim- ilar basic structure— dexamethasone (DEX), 16’-methyl- prednisonole (MP), and 16’-methylprednisolone acetate (MPA)—were used as models for the entrapment and re- lease of bioactive agents. DEX, MP, and MPA were en- trapped into starch-based microparticles at 10% wt/wt of the starch-based polymer and the loading efficiencies, as well as the release profiles, were evaluated. Differences were found for the loading efficiencies of the three corticosteroids, with DEX and MPA being the most successfully loaded (82 and 84%, respectively), followed by MP (51%). These differ- ences might be explained based on the differential distribu- tion of the molecules within the matrix of the microparticles. Furthermore, a differential burst release was observed in the first 24 h for all corticosteroids with DEX and MP being

INTRODUCTION

Because of the considerable advantage of their clear- ance from the body after the release of therapeutic agents, biodegradable polymers are among the most widely used materials for controlled drug delivery applications.1 Starch-based polymers have been stud- ied mainly by Reis et al.2–5 for a wide range of bone- related applications, ranging from tissue engineering scaffolds,6 –11 to bone cements,12–14 and drug delivery

Correspondence to: G. A. Silva; e-mail: gsilva@dep. uminho.pt.

Contract grant sponsor: Portuguese Foundation for Sci- ence and Technology; contract grant number: SFRH/BD/ 4648/2001

Contract grant sponsor: Portuguese Foundation for Sci- ence and Technology through funds from the POCTI and/or FEDER programs

© 2005 Wiley Periodicals, Inc.

more pronounced (around 25%), whereas only 12% of MPA was released during the same time period. Whereas the water uptake profile can account for this first stage burst release, the subsequent slower release stage was mainly attributed to degradation of the microparticle network. Dif- ferences in the release profiles can be explained based on the structure of the molecule, because MPA, a more bulky and hydrophobic molecule, is released at a slower rate compared with DEX and MP. In this work, it is shown that these carriers were able to sustain a controlled release of the entrapped corticosteroids over 30 days, which confirms the potential of these systems to be used as carriers for the delivery of bioactive agents.