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dc.contributor.authorN'Da, David D.
dc.contributor.authorBreytenbach, Jaco C.
dc.contributor.authorLegoabe, Lesetja J.
dc.contributor.authorBreytenbach, J. Wilma
dc.date.accessioned2014-08-05T09:30:20Z
dc.date.available2014-08-05T09:30:20Z
dc.date.issued2009
dc.identifier.citationN'Da, D.D. et al. 2009. Synthesis and in vitro transdermal penetration of methoxypoly(ethylene glycol) carbonate derivatives of stavudine. Medicinal chemistry, 5(6):497-506. [https://doi.org/10.2174/157340609790170470]
dc.identifier.issn1573-4064
dc.identifier.issn1875-6638 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/11028
dc.identifier.urihttp://www.eurekaselect.com/85507/article
dc.identifier.urihttps://doi.org/10.2174/157340609790170470
dc.description.abstractThe objective of this study was to synthesize derivatives of the anti-HIV drug stavudine (d4T) with more favourable physicochemical properties for transdermal delivery in an effort to increase transdermal penetration of stavudine and thus reduce the severe side effects associated with the dose-dependent oral therapy. The synthesis, hydrolytic stability, and in vitro human skin permeation flux of a series of novel methoxypoly(ethylene glycol) (MPEG) carbonates of stavudine are reported. The carbonates were synthesized in a two-step process by coupling the MPEG promoiety of various chain lengths to C-5' of d4T. In kinetic studies the carbonates proved to be markedly stable in weakly acidic phosphate medium (pH 5.0) with half-lives ranging from 16 to 58 days. The aqueous solubility increased as the ethylene oxide chain lengthened. However, there was no significant increase in the estimated solubility in octanol. In vitro in the phosphate buffer (200 mM; pH 5.0) almost all carbonates permeate the human skin. However, the most effective penetrant, the derivative with 3 ethylene oxide units in the side chain, exhibited a flux of 26.1 nmol/cm2/h as compared to 59.15 nmol/cm2/h of the parent drug stavudine. Thus, no permeation enhancement was observed during this study.en_US
dc.language.isoenen_US
dc.publisherBentham Scienceen_US
dc.subjectTransdermal penetrationen_US
dc.subjectMethoxypoly(ethylene glycol) (MPEG)en_US
dc.subjectEthylene oxide (EO)en_US
dc.subjectStavudineen_US
dc.titleSynthesis and in vitro transdermal penetration of methoxypoly(ethylene glycol) carbonate derivatives of stavudine (3TC)en_US
dc.typeArticleen_US
dc.contributor.researchID20883072 - N'Da, David Dago
dc.contributor.researchID10187081 - Breytenbach, Johanna Wilhelmina
dc.contributor.researchID12902608 - Legoabe, Lesetja Jan
dc.contributor.researchID10059768 - Breytenbach, Jaco Cornelius


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