Formulation of Natural Oil Nano-Emulsions for the Topical Delivery of Clofazimine, Artemisone and Decoquinate
The aim of this study was to formulate nano-emulsions comprising natural oils and the active pharmaceutical ingredients (APIs) clofazimine (CLF), artemisone (ATM) and decoquinate (DQ) in order to determine effectiveness of the nano-emulsions for topical delivery of the APIs. The APIs alone do not possess suitable physicochemical properties for topical drug delivery.
Nano-emulsions were formulated with olive and safflower oils encapsulating the APIs. Skin diffusion and tape stripping studies were performed. By using the lactate dehydrogenase (LDH) assay, in vitro toxicity studies were carried out on immortalized human keratinocytes (HaCaT) cell line to determine cytotoxicities due to the APIs and the nano-emulsions incorporating the APIs.
The nano-emulsions were effective in delivering the APIs within the stratum corneum-epidermis and the epidermis-dermis, were non-cytotoxic towards HaCaT cell lines (p < 0.05) and inhibited Mycobacterium tuberculosis in vitro.
Natural oil nano-emulsions successfully deliver CLF, ATM and DQ and in principle could be used as supplementary topical treatment of cutaneous tuberculosis (CTB).
Key Wordsartemisone clofazimine cutaneous tuberculosis decoquinate nano-emulsions
Middlebrook 7HP Broth Base and Middlebrook AODC growth supplement
Analysis of variance
Active pharmaceutical ingredient
Phage attachment site
Dulbecco’s modified eagle medium
Fetal bovine serum
Glycerol-alanine-salts containing iron
Green fluorescent protein
Immortalized human keratinocyte cells
High performance liquid chromatography
Hygromycin B resistance gene
Limit of detection
- Log D
Octanol-water distribution coefficient
Limit of quantitation
90% Minimum inhibitory concentration
Non-essential amino acids
Olive oil nano-emulsion containing clofazimine
Olive oil nano-emulsion containing artemisone
Olive oil nano-emulsion containing decoquinate
Olive oil nano-emulsion containing clofazimine, artemisone and decoquinate
Olive oil nano-emulsion placebo
Optical density reading taken at 600 nm
Phosphate buffer solution
Reactive oxygen species
Safflower oil nano-emulsion containing clofazimine
Safflower oil nano-emulsion containing artemisone
Safflower oil nano-emulsion containing decoquinate
Safflower oil nano-emulsion containing clofazimine, artemisone and decoquinate
Safflower oil nano-emulsion placebo
Acknowledgments and Disclosures
This research project was supported by the South African Medical Research Council (MRC) Flagship Project Scheme with funds from the National Treasury under its Economic Competitiveness and Support Package, The authors thank the Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, South Africa and the National Research Foundation of South Africa for their financial contribution to this project [grant number CPRR13091742482]. Marelize Pretorius of the Statistical Consultation Services is thanked for the statistical analysis of the data and Ms. A. Brümmer for the cytotoxicity studies at the North-West University, Potchefstroom Campus, South Africa. Any opinion, findings and conclusions, or recommendations expressed in this material are those of the authors and therefore the NRF does not accept any liability in regard thereto. The authors declare no conflict of interest.
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