Lipid-Based Ionic-Liquid-Mediated Nanodispersions as Biocompatible Carriers for the Enhanced Transdermal Delivery of a Peptide Drug

Uddin, S. and Islam, M.R. and Chowdhury, M.R. and Wakabayashi, R. and Kamiya, N. and Moniruzzaman, M. and Goto, M. (2021) Lipid-Based Ionic-Liquid-Mediated Nanodispersions as Biocompatible Carriers for the Enhanced Transdermal Delivery of a Peptide Drug. ACS Applied Bio Materials, 4 (8). pp. 6256-6267. ISSN 25766422

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Abstract

Lipid-based biocompatible ionic liquids (LBILs) have attracted attention as carriers in transdermal drug delivery systems (TDDSs) because of their lipophilic character. In this study, we report the formulation of a peptide-LBIL complex microencapsulated in an oil phase as a potential carrier for the transdermal delivery of leuprolide acetate as a model hydrophilic peptide. The peptide-LBIL complexes were prepared via a water-in-oil emulsion composed of 1,2-dimyristoyl-sn-glycerol-3-ethyl-phosphatidylcholine (EDMPC), a fatty acid (stearic, oleic, and linoleic acid)-based LBIL, and cyclohexane followed by freeze-drying to remove the water and cyclohexane. Then, the peptide-LBIL complexes were nanodispersed and stabilized in isopropyl myristate (IPM) using sorbitol laurate (Span-20). Ionic-liquid-in-oil nanodispersions (IL/O-NDs) were prepared with varying weight ratios of LBILs and Span-20 as the surfactant and the cosurfactant, respectively. Keeping the overall surfactant constant at 10 wt in IPM, a 5:5 wt ratio of surfactant (IL) and cosurfactant (Span-20) in the IL/O-NDs significantly (p < 0.0001) increased the physiochemical stability, drug-loading capacity, and drug encapsulation efficiency. The in vitro and in vivo peptide delivery across the skin was increased significantly (p < 0.0001) using IL/O-NDs, compared with non-IL-treated groups. Of all of the LBIL-based formulations, EDMPCLinoleate/O-ND was considered the most preferable for a TDDS based on the pharmacokinetic parameters. The transdermal delivery flux with EDMPCLinoleate/O-ND was increased 65-fold compared with the aqueous delivery vehicle. The IL/O-NDs were able to deform the lipid and protein arrangements of the skin layers to enhance the transdermal permeation of the peptide. In vitro and in vivo cytotoxicity studies of the IL/O-NDs revealed the biocompatibility of the LBIL-based formulations. These results indicated that IL/O-NDs are promising biocompatible carriers for lipid-peptide TDDSs. © 2021 American Chemical Society.

Item Type: Article
Additional Information: cited By 15
Uncontrolled Keywords: Biocompatibility; Controlled drug delivery; Cyclohexane; Drug products; Emulsification; Emulsions; Ionic liquids; Linoleic acid; Nanocapsules; Peptides; Surface active agents, Drug encapsulation efficiency; Drug loading capacity; Lipophilic character; Pharmacokinetic parameters; Transdermal delivery; Transdermal drug delivery systems; Transdermal permeation; Water in oil emulsions, Targeted drug delivery, drug carrier; ionic liquid; linoleic acid; peptide; surfactant; water, chemistry; skin absorption, Drug Carriers; Ionic Liquids; Linoleic Acid; Peptides; Skin Absorption; Surface-Active Agents; Water
Depositing User: Mr Ahmad Suhairi UTP
Date Deposited: 10 Nov 2023 03:29
Last Modified: 10 Nov 2023 03:29
URI: https://khub.utp.edu.my/scholars/id/eprint/14575

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