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Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension

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Abstract

Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs possess certain ideal physicochemical properties. The lack thereof would require that APIs be included in drug delivery vehicles to enhance skin permeation. Hence, diclofenac was incorporated into various drug delivery vehicles (i.e., nano-emulsions, nano-emulgels, and a colloidal suspension containing drug-loaded nanoparticles) to investigate the transdermal delivery thereof, while nano-emulsions and nano-emulgels had varying concentrations of evening primrose oil (EPO). The aim of the study was to compare the topical and transdermal diclofenac delivery from the different types of vehicles and to investigate the influence the different EPO concentrations had on diclofenac delivery. After characterization, membrane release studies were performed (to determine whether the API was successfully released from the vehicle) followed by in vitro skin diffusion studies and tape stripping (to establish whether the vehicles assisted the API in reaching the target site (transdermal delivery)). Lastly, cytotoxicity studies were conducted via methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on human keratinocyte (HaCaT) cells. Results showed minimal cytotoxic effects at concentrations equivalent to that which had permeated through the skin, while the membrane release and in vitro skin diffusion studies indicated that the nano-emulsions and the 10% EPO vehicles increased API release and diffusion when compared to the other vehicles. However, the colloidal suspension had the highest concentrations of API within the skin. Hence, all the vehicles were non-toxic and effectively delivered diclofenac through the transdermal route.

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Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

A sincere word of appreciation to Dr. Marike Cockeran at the Statistical Consultation Services, North-West University (NWU), for the statistical data analysis and Prof. Frank van der Kooy from the Analytical Technology Laboratory (ATL), Pharmacen™, NWU for his excellent guidance during HPLC method validation. Dr. Anine Jordaan from the Laboratory for Electron Microscopy (LEM), Chemical Resource Beneficiation, NWU, performed the transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analysis.

Funding

The authors express gratitude to the research funds of Prof. M. Gerber and The Centre of Excellence for Pharmaceutical Sciences (Pharmacen™) of the North-West University (NWU), South Africa, for the financial support and facilities provided to complete this study.

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Authors and Affiliations

  1. Centre of Excellence for Pharmaceutical Sciences (Pharmacen™), North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa

    Estelle-Vionè Louw, Wilna Liebenberg, Clarissa Willers & Minja Gerber

  2. School of Pharmacy, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, Cape Town, 7535, South Africa

    Admire Dube & Marique E. Aucamp

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Contributions

E-VL performed the experiments, interpreted the results, and drafted the original manuscript. MG, WL, and MEA supervised, attained funding for the project, and assisted in writing the manuscript through critical reviewing and editing. MG conceptualized and designed the project. CW maintained the in vitro cell cultures and assisted with the cytotoxicity experiments. AD provided assistance and critical input into the formulation of drug delivery vehicles, especially the nanoparticles. All authors have read, edited, and approved the final version of the manuscript.

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Correspondence to Minja Gerber.

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Ethical approval and consent to participate

The study was approved by the North-West University Health Research Ethics Committee (NWU-HREC) (Ethics approval no: NWU-00111–17-A1-10) and conformed with the Declaration of Helsinki. Written informed consent was obtained from each patient.

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All the authors gave their consent for publication of this manuscript in the CRS Local Chapter Special Issue of Drug Delivery and Translational Research (DDTR). Although informed consent was attained from all participants, the manuscript contains no personal data of any participant in any form. No children were included in the study.

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Louw, EV., Liebenberg, W., Willers, C. et al. Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension. Drug Deliv. and Transl. Res. 13, 1372–1389 (2023). https://doi.org/10.1007/s13346-022-01267-7

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  • DOI: https://doi.org/10.1007/s13346-022-01267-7

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