Protein encapsulation in polymeric microneedles by photolithography

Abstract

Background

Recent interest in biocompatible polymeric microneedles for the delivery of biomolecules has propelled considerable interest in fabrication of microneedles. It is important that the fabrication process is feasible for drug encapsulation and compatible with the stability of the drug in question. Moreover, drug encapsulation may offer the advantage of higher drug loading compared with other technologies, such as drug coating.

Methods and results

In this study, we encapsulated a model protein drug, namely, bovine serum albumin, in polymeric microneedles by photolithography. Drug distribution within the microneedle array was found to be uniform. The encapsulated protein retained its primary, secondary, and tertiary structural characteristics. In vitro release of the encapsulated protein showed that almost all of the drug was released into phosphate buffered saline within 6 hours. The in vitro permeation profile of encapsulated bovine serum albumin through rat skin was also tested and shown to resemble the in vitro release profile, with an initial release burst followed by a slow release phase. The cytotoxicity of the microneedles without bovine serum albumin was tested in three different cell lines. High cell viabilities were observed, demonstrating the innocuous nature of the microneedles.

Conclusion

The microneedle array can potentially serve as a useful drug carrier for proteins, peptides, and vaccines.

Video abstract

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Keywords:

• poly (ethylene glycol) diacrylate
• microneedles
• protein stability
• photolithography
• biocompatibility

Acknowledgments

The authors would like to acknowledge Joleen Lim for her assistance with imaging the microneedle samples. We also thank Sathya Unudurthi, Sandeep Shelar, and Jun Yan for their help with the experiments in this study, and Brian W Dymock for his careful proofreading. We would also like to thank Joyce Lee and Aparna Saigal for their assisstance in preparation of the video abstract. Jaspreet Singh is the recipient of a National University of Singapore research scholarship. This study was supported by a startup grant from the National University of Singapore.

Disclosure

The authors report no conflicts of interest in this work.