In vitro and in vivo Research of Sustained Release ketotifen fumarate for Treatment of asthma

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology Vol. 24; no. 5
• Main Authors: Zhang, Lihong, Peng, Yahong, Ren, Ming, Li, Yanyan, Tang, Hui
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.05.2022; Springer Nature B.V
• Subjects: Asthma; Bioavailability; Characterization and Evaluation of Materials; Chemistry and Materials Science; Controlled release; Cube texture; Drug delivery; Entrapment; Gels; Image transmission; Inorganic Chemistry; Irritation; Lasers; Lipids; Materials Science; Nanoparticles; Nanotechnology; Optical Devices; Optics; Pharmacokinetics; Photonics; Physical Chemistry; Poloxamers; Research Paper; Skin; Sustained release; Transmission electron microscopy; Viscosity; Zeta potential; Ex vivo studies; Cubosomes; Ketotifen fumarate; Drug delivery; Transdermal; Nanomedicine; Pharmacokinetic studies
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-022-05475-7

Ketotifen fumarate, a mast cell stabilizer, is frequently prescribed in low doses to manage chronic asthma of allergic origin. However, it shows several limitations, including high-first pass metabolism, poor oral bioavailability (50%), and short half-life of 3 h. In this work, a novel non-invasive transdermal ketotifen fumarate–loaded cubosome-laden gel was formulated to achieve sustained drug release for effective treatment of asthma. Cubosomes were prepared by fragmentation method by SolEmuls technology using phytantriol and Pluronic F127. The cubosomes were characterized for size, zeta potential, morphology, entrapment efficacy, drug content, viscosity, pH, and texture analysis profiles. Cryo-transmission electron microscopy images confirmed the cubic crystalline phase of cubosomes. The cubosomes particle size, viscosity, and entrapment efficacy increase with the level of lipid phytantriol. The ex vivo permeation study showed sustained ketotifen fumarate release for 120 h from cubosomal gels compared to 48 h from control gel. A rabbit skin irritation study showed no sign of irritation after application of cubosomal gel. The pharmacokinetic parameters in the rat model showed 6.9-fold higher bioavailability with cubosomal gel compared to control gel. In conclusion, the study demonstrated the potential of cubosomes for effective transdermal delivery of ketotifen fumarate to replace oral tablet dosage forms. Graphical abstract