Design, Development, and Characterization of Imiquimod-Loaded Chitosan Films for Topical Delivery
- 87 Downloads
Aldara™ (5% w/w imiquimod) topical cream is approved by the US FDA for the treatment of superficial basal cell carcinoma. However, the cream formulation suffers from dose variability, low drug availability due to the incomplete release, and poor patient compliance. To achieve sustained and complete release of imiquimod, chitosan films were prepared by casting using propylene glycol as a plasticizer. Chitosan films had appropriate physicochemical characteristics for wound dressing and excellent content uniformity and maintained the original physical form of imiquimod. Films were capable of releasing a defined dose of imiquimod over a period of 7 days. The bioactivity of imiquimod was not affected by its entrapment in chitosan matrix as indicated by the results of in vitro growth inhibition assay. In addition, the film formulation showed significantly (p ˂ 0.05) higher drug accumulation in the skin when compared to commercial cream formulation.
Key Wordschitosan imiquimod basal cell carcinoma film formulation topical drug delivery
The authors would like to thank Hanna Iaizzo and Mamta Kapoor for conducting the preliminary studies. The mechanical tests were performed at the Characterization Facility, University of Minnesota, Minneapolis, MN.
- 14.Layek B, Singh J. 8 - Chitosan for DNA and gene therapy A2 - Jennings, J. Amber. In: Bumgardner JD, editor. Chitosan Based Biomaterials Volume 2: Woodhead Publishing; 2017. p. 209–44.Google Scholar
- 17.Rinaudo M. Chitin and chitosan: properties and applications. Prog Polym Sci. 2006;31(7):603–32. https://doi.org/10.1016/j.progpolymsci.2006.06.001.CrossRefGoogle Scholar
- 22.Córdoba-Díaz M, Nova M, Elorza B, Córdoba-Díaz D, Chantres JR, Córdoba-Borrego M. Validation protocol of an automated in-line flow-through diffusion equipment for in vitro permeation studies. J Control Release. 2000;69(3):357–67. https://doi.org/10.1016/S0168-3659(00)00306-0.CrossRefPubMedGoogle Scholar
- 23.Layek B, Sadhukha T, Prabha S. Glycoengineered mesenchymal stem cells as an enabling platform for two-step targeting of solid tumors. Biomaterials. 2016;88:97–109. https://doi.org/10.1016/j.biomaterials.2016.02.024.CrossRefPubMedGoogle Scholar
- 27.Sasikala L, Durai B, Rathinamoorthy R. Manuka honey loaded chitosan hydrogel films for wound dressing applications. 2013.Google Scholar
- 31.Allegrini P, Razzetti G, Bologna A, Magrone D, Ventimiglia G. A process for the purification of imiquimod. Google Patents; 2007.Google Scholar
- 33.Wiedmann TS, Naqwi A. Pharmaceutical salts: theory, use in solid dosage forms and in situ preparation in an aerosol. Asian J Pharm Sci. 2016. https://doi.org/10.1016/j.ajps.2016.07.002.
- 40.S-h H, Whu SW, Tsai C-L, Wu Y-H, Chen H-W, Hsieh K-H. Chitosan as scaffold materials: effects of molecular weight and degree of deacetylation. J Polym Res. 2004;11(2):141–7. https://doi.org/10.1023/B:JPOL.0000031080.70010.0b.CrossRefGoogle Scholar
- 43.Kowapradit J, Opanasopit P, Ngawhiranpat T, Apirakaramwong A, Rojanarata T, Ruktanonchai U, et al. Methylated N-(4-N,N-dimethylaminobenzyl) chitosan, a novel chitosan derivative, enhances paracellular permeability across intestinal epithelial cells (Caco-2). AAPS PharmSciTech. 2008;9(4):1143–52. https://doi.org/10.1208/s12249-008-9160-7.CrossRefPubMedPubMedCentralGoogle Scholar