Modulating the release of pharmaceuticals from lipid cubic phases using a lipase inhibitor

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:573

Article

Dully, Michele¹  Brasnett, Christopher²  Djeghader, Ahmed¹  Seddon, Annela^2,3  Neilan, John⁴  Murray, David⁴  Butler, James⁴  Soulimane, Tewfik¹  Hudson, Sarah P.¹ 

[1] Univ Limerick, Bernal Inst, Dept Chem Sci, Castletroy, Co Limerick, Ireland

[2] Univ Bristol, Sch Phys, Tyndall Ave, Bristol BS8 1FD, Avon, England

[3] Univ Bristol, Bristol Ctr Funct Nanomat, HH Wills Phys Lab, Tyndall Ave, Bristol BS8 1FD, Avon, England

[4] Cook Ireland Ltd, OHalloran Rd, Castletroy, Co Limerick, Ireland

关键词: Lipid cubic phase;    Controlled delivery;    Hydrophobic active pharmaceuticals;    Enzyme degradation;    Lipase inhibitor;    SAXS;   

DOI  :  10.1016/j.jcis.2020.04.015

来源: Elsevier

【 摘 要 】

Lipid cubic phase formulations have gained recognition as potential controlled delivery systems for a range of active pharmaceutical and biological agents on account of their desirable physiochemical properties and ability to encapsulate both hydrophobic and hydrophilic molecules. The most widely studied lipid cubic systems are those of the monoacylglycerol lipid family. These formulations are susceptible to lipolysis by a variety of enzymes, including lipases and esterases, which attack the ester bond present on the lipid chain bridging the oleic acid component to the glycerol backbone. The release of poorly soluble molecules residing in the lipid membrane portions of the phase is limited by the breakdown of the matrix; thus, presenting a potential means for further controlling and sustaining the release of therapeutic agents by targeting the matrix stability and its rate of degradation. The aims of the present study were twofold: to evaluate an approach to regulate the rate of degradation of lipid cubic phase drug delivery systems by targeting the enzyme interactions responsible for their demise; and to study the subsequent drug release profiles from bulk lipid cubic gels using model drugs of contrasting hydrophobicity. Here, hybrid materials consisting of cubic phases with monoacylglycerol lipids of different chain lengths formulated with a potent lipase inhibitor tetrahydrolipstatin were designed. Modulation of the release of a hydrophobic model pharmaceutical, a clofazimine salt, was obtained by exploiting the matrices' enzyme-driven digestion. A stable cubic phase is described, displaying controlled degradation with at least a 4-fold improvement compared to the blank systems shown in inhibitor-containing cubic systems. Sustained release of the model hydrophobic pharmaceutical was studied over 30 days to highlight the advantage of incorporating an inhibitor into the cubic network to achieve tunable lipid release systems. This is done without negatively affecting the structure of the matrix itself, as shown by comprehensive small-angle x-ray scattering experiments. (C) 2020 The Authors. Published by Elsevier Inc.

【 授权许可】

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