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).
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- 7H9/OADC :
Middlebrook 7HP Broth Base and Middlebrook AODC growth supplement
- ANOVA :
Analysis of variance
- API :
Active pharmaceutical ingredient
- ATM :
- attB :
Phage attachment site
- CFU :
- CLF :
- CTB :
- DMEM :
Dulbecco’s modified eagle medium
- DMSO :
- DQ :
- ED :
- EDTA :
- EE% :
- FBS :
Fetal bovine serum
- GAST/Fe :
Glycerol-alanine-salts containing iron
- GFP :
Green fluorescent protein
- HaCaT :
Immortalized human keratinocyte cells
- HPLC :
High performance liquid chromatography
- Hyg 50 :
Hygromycin B resistance gene
- INH :
- LDH :
- LOD :
Limit of detection
- Log D :
Octanol-water distribution coefficient
- LOQ :
Limit of quantitation
- M.tb :
- MDR-TB :
- MIC 90 :
90% Minimum inhibitory concentration
- NEAA :
Non-essential amino acids
- O :
- O1 :
Olive oil nano-emulsion containing clofazimine
- O2 :
Olive oil nano-emulsion containing artemisone
- O3 :
Olive oil nano-emulsion containing decoquinate
- O4 :
Olive oil nano-emulsion containing clofazimine, artemisone and decoquinate
- O5 :
Olive oil nano-emulsion placebo
- OD 600 :
Optical density reading taken at 600 nm
- PBS :
Phosphate buffer solution
- Pen/Strep :
- PVDF :
Reactive oxygen species
- S :
- S1 :
Safflower oil nano-emulsion containing clofazimine
- S2 :
Safflower oil nano-emulsion containing artemisone
- S3 :
Safflower oil nano-emulsion containing decoquinate
- S4 :
Safflower oil nano-emulsion containing clofazimine, artemisone and decoquinate
- S5 :
Safflower oil nano-emulsion placebo
- SCE :
- TB :
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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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Burger, C., Aucamp, M., du Preez, J. et al. Formulation of Natural Oil Nano-Emulsions for the Topical Delivery of Clofazimine, Artemisone and Decoquinate. Pharm Res 35, 186 (2018). https://doi.org/10.1007/s11095-018-2471-9
- cutaneous tuberculosis