Zein Microneedles for Localized Delivery of Chemotherapeutic Agents to Treat Breast Cancer: Drug Loading, Release Behavior, and Skin Permeation Studies
- 160 Downloads
Localized delivery of chemotherapeutic agents to treat breast cancer could limit their adverse drug reactions. The aim of this study was to investigate the influence of physico-chemical properties of chemotherapeutic agents in their loading, release behavior, and skin permeation using microneedles. Zein microneedles were fabricated using the micromolding technique containing 36 microneedles in a 1-cm2 area. These microneedles were loaded with two anti-breast cancer drugs, tamoxifen and gemcitabine, having different water solubilities. Entrapment or surface coating of chemotherapeutic agents in zein microneedles was optimized to achieve greater loading efficiency. The greatest loading achieved was 607 ± 21 and 1459 ± 74 μg for tamoxifen and gemcitabine using the entrapment approach, respectively. Skin permeation studies in excised porcine skin showed that the coating on microneedles approach results in greater skin deposition for tamoxifen; while the poke-and-patch approach would provide greater skin permeation for gemcitabine. Taken together, it can be concluded that different loading strategies and skin penetration approaches have to be studied for delivery of small molecules using polymeric microneedles.
KEY WORDStamoxifen gemcitabine zein microneedles drug release skin permeation
This work was financially supported by BITS Pilani. The texture analyzer and multimode plate reader were procured using a grant from the Department of Science and Technology—Fund for Improvement of Science and Technology infrastructure (DST FIST).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
- 2.Junwei L, Mingtao Z, Shan H, Chunyi T. Microneedle patches as drug and vaccine delivery platform. Curr Med Chem. 2017;24(22):2413–22. https://doi.org/10.2174/0929867324666170526124053. Google Scholar
- 5.Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE, et al. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine. 2006;24(10):1653–64. https://doi.org/10.1016/j.vaccine.2005.09.049.CrossRefPubMedGoogle Scholar
- 12.Donnelly RF, Majithiya R, Singh TR, Morrow DI, Garland MJ, Demir YK, et al. Design, optimization and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique. Pharm Res. 2011;28(1):41–57. https://doi.org/10.1007/s11095-010-0169-8.CrossRefPubMedGoogle Scholar
- 28.Poulin P, Chen Y-H, Ding X, Gould SE, Hop CE, Messick K, et al. Prediction of drug distribution in subcutaneous xenografts of human tumor cell lines and healthy tissues in mouse: application of the tissue composition-based model to antineoplastic drugs. J Pharm Sci. 104(4):1508–21. https://doi.org/10.1002/jps.24336.
- 31.Osborne TB. Classification of vegetable proteins. In: Osborne TB, editor. The vegetable proteins. New York: Longmans, Green and Co.; 1924. p. 25–35.Google Scholar
- 34.Wilson CM. Proteins of the kernel. In: Watson SA, Ramstad PE, editors. Corn: chemistry and technology. St. Paul: Am. Assoc. Cereal Chem; 1987. p. 273–310.Google Scholar
- 36.Jane J, Lim S, Paetau I, Spence K, Wang S. Biodegradable plastics made from agricultural biopolymers. ACS Publications; 1994.Google Scholar