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The development of simple flow injection analysis tandem mass spectrometric methods for the cutaneous determination of peptide-modified cationic gemini surfactants used as gene delivery vectors.

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dc.contributor.authorAl-Dulaymi, Mays
dc.contributor.authorMichel, Deborah
dc.contributor.authorChitanda, Jackson M
dc.contributor.authorBadea, ildiko
dc.contributor.authorEl-Aneed, Anas
dc.date.accessioned2019-09-20T15:15:09Z
dc.date.available2019-09-20T15:15:09Z
dc.date.issued2018-09-10
dc.description.abstractDiquaternary ammonium gemini surfactants are a class of non-viral gene delivery vectors, primarily studied for their dermal applications. However, their biological fate has rarely been investigated. In this work, we developed simple flow injection analysis tandem mass spectrometric methods, (FIA)-MS/MS, to understand the fate and biodistribution of topically applied gemini surfactant-based therapeutics in an ex-vivo skin model. Three peptide-modified gemini surfactants with varied structures and transfection efficiencies were evaluated. For each compound, two methods were developed to quantify their presence in skin tissue and in phosphate buffered saline (PBS). The methods were developed using single-point calibration mode. Skin penetration was assessed on CD1 mice dorsal skin tissue mounted in a Franz diffusion cell after extraction. Amongst the five evaluated liquid-liquid extraction protocols, the Folch method provides the highest extraction efficiency for all compounds. Weak cationic exchange solid phase extraction was also used to further isolate gemini surfactants from endogenous skin lipids. FIA–MS/MS analysis of the skin revealed that all compounds were detected in the skin with minimal partition into the PBS compartment, which represents circulation. Interestingly, the detected amounts of gemini lipids in the skin were correlated with their transfection efficiencies.en_US
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada (NSERC), Canadian Institutes of Health Research Training grant in Health Research Using Synchrotron Techniques (CIHR-THRUST), Western Economic Diversification Canada, College of Pharmacy and Nutritionen_US
dc.description.versionPeer Revieweden_US
dc.identifier.citationAl-Dulaymi, M., Michel, D., Chitanda, JM, Badea, I., El-Aneed, A. (2018) The Development of Simple Flow Injection Analysis Tandem Mass Spectrometric Methods for the Cutaneous Determination of Peptide-Modified Cationic Gemini Surfactants Used as Gene Delivery Vectors. J Pharm Biomed Anal. 2018 Sept. 10, 159: 536-547. https://doi.org/10.1016/j.jpba.2018.06.063en_US
dc.identifier.doi10.1016/j.jpba.2018.06.063
dc.identifier.pmid30056225
dc.identifier.urihttp://hdl.handle.net/10388/12341
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivs 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/ca/*
dc.titleThe development of simple flow injection analysis tandem mass spectrometric methods for the cutaneous determination of peptide-modified cationic gemini surfactants used as gene delivery vectors.en_US
dc.typePostprinten_US

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