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

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Show simple item record Dully, Michele Bhattacharya, Shayon Verma, Vivek Murray, David Thompson, Damien Soulimane, Tewfik Hudson, Sarah P. 2021-10-05T07:39:14Z 2021-10-05T07:39:14Z 2022
dc.description peer-reviewed en_US
dc.description.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 en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries Journal of Colloid and Interface Science;607,pp. 978–991
dc.subject Lipid cubic phase en_US
dc.subject Pancreatic lipase en_US
dc.subject Tetrahydrolipstatin en_US
dc.title Balanced lipase interactions for degradation-controlled paclitaxel release from lipid cubic phase formulations en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1016/j.jcis.2021.09.024
dc.contributor.sponsor IRC en_US
dc.contributor.sponsor SFI en_US
dc.relation.projectid EPSPG/2016/85 en_US
dc.relation.projectid 15/CDA/3491 en_US
dc.relation.projectid 12/RC/2275_P2 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US

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