Maximized mucoadhesion and skin permeation of anti-AIDS-loaded niosomal gels.
The low permeability of the anti-AIDS, tenofovir, limits its antiretroviral clinical potency. The proposed study aimed at assessing the critical biological responses of tenofovir through the development and optimization of its surfactant-based niosomal gels intended for vaginal delivery. Fatty acid chain length of the amphiphile and cholesterol loading were optimized using a 3² full factorial design. Vesicular size, shape and surface charge, drug entrapment efficiency, in vitro release, and skin permeation were used to assess the gels. In addition, their biological performance on Lactobacillus crispatus viability and mucoadhesion to porcine vaginal tissue was also assessed. Within the design space, mucoadhesion percentage ranged from 6.2% to 28.6% and increased nonlinearly by decreasing niosomal vesicular size and linearly by increasing surface charge. Moreover, these gels were not cytotoxic to Lactobacillus crispatus for 48 h. For maximizing tenofovir entrapment, percutaneous permeation, and mucoadhesion while achieving sustained-release features, an optimum formulation was proposed with the shortest length of fatty chain and 0.48 mM cholesterol content. Overall, applying quality by design paradigm to the development of tenofovir niosomal gels not only offered a promising nanomedicine for the vaginal microbicide delivery but also unveiled the critical formulation interactions influencing its biological performance.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Ahmed S
AS
Zidan
Muhammad J
MJ
Habib
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D000268:Adhesiveness; D000279:Administration, Cutaneous; D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D002784:Cholesterol / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D004339:Drug Compounding; D005260:Female; D006601:Hexoses / Q000737:chemistry; D066298:In Vitro Techniques; D009092:Mucous Membrane / Q000378:metabolism*; D063065:Organophosphonates / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D034421:Sus scrofa; D000068698:Tenofovir; D057968:Transdermal Patch; D014621:Vagina / Q000378:metabolism*; D014622:Vaginal Creams, Foams, and Jellies
D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D006601:Hexoses; D063065:Organophosphonates; D013501:Surface-Active Agents; D014622:Vaginal Creams, Foams, and Jellies; C014822:sorbitan monolaurate; D002784:Cholesterol; D000068698:Tenofovir; D000225:Adenine
Formulation; Hydrogels; Mucosal drug delivery; Quality by Design; Surfactants; Transdermal; mucoadhesion; niosomal gels; tenofovir; vaginal delivery