Affordable Access

deepdyve-link
Publisher Website

Balanced lipase interactions for degradation-controlled paclitaxel release from lipid cubic phase formulations.

Authors
  • Dully, Michele1
  • Bhattacharya, Shayon2
  • Verma, Vivek1
  • Murray, David3
  • Thompson, Damien4
  • Soulimane, Tewfik5
  • Hudson, Sarah P6
  • 1 Department of Chemical Sciences, SSPC the Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland. , (Ireland)
  • 2 Department of Physics, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland. , (Ireland)
  • 3 COOK Ireland Limited, O'Halloran Rd, Castletroy, Co., Limerick, Ireland. , (Ireland)
  • 4 Department of Physics, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland. Electronic address: [email protected] , (Ireland)
  • 5 Department of Chemical Sciences, SSPC the Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland. Electronic address: [email protected] , (Ireland)
  • 6 Department of Chemical Sciences, SSPC the Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland. Electronic address: [email protected] , (Ireland)
Type
Published Article
Journal
Journal of Colloid and Interface Science
Publisher
Elsevier
Publication Date
Sep 24, 2021
Volume
607
Issue
Pt 2
Pages
978–991
Identifiers
DOI: 10.1016/j.jcis.2021.09.024
PMID: 34571316
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Lipid cubic phase (LCP) formulations enhance the intestinal solubility and bioavailability of hydrophobic drugs by reducing precipitation and facilitating their mass transport to the intestinal surface for absorption. LCPs with an ester linkage connecting the acyl chain to the glycerol backbone (monoacylglycerols), are susceptible to chemical digestion by several lipolytic enzymes including lipases, accelerating the release of hydrophobic agents from the lipid bilayers of the matrix. Unlike regular enzymes that transform soluble substrates, lipolytic enzymes act at the interface of water and insoluble lipid. Therefore, compounds that bind to this interface can enhance or inhibit the activity of enzymes to varying extent. Here, we explore how the lipolysis rate can be tuned by the interfacial interaction of porcine pancreatic lipase with monoolein LCPs containing a known lipase inhibitor, tetrahydrolipstatin. Release of the Biopharmaceutical Classification System (BCS) class IV drug, paclitaxel, from the inhibitor-modified LCP was examined in the presence of lipase and its effectors colipase and calcium. By combining experimental dynamic digestion studies, thermodynamic measurements and molecular dynamics simulations of the competitive inhibition of lipase by tetrahydrolipstatin, we reveal the role and mode of action of lipase effectors in creating a precisely-balanced degradation-controlled LCP release system for the poorly soluble paclitaxel drug. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times