Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across Porcine Skin and Possible Interaction with Fish Oil Fatty Acids
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Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle, CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel, oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear skin was then evaluated. Furthermore, the effects of the omega-3 fatty eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from fish oil on skin permeation were investigated by means of nuclear magnetic resonance (NMR) and computerised molecular modelling docking experiments. The highest drug permeation was achieved with the bigel formulation that proved to be the most effective vehicle in delivering CoQ10 across the skin membrane due to a combination of its adhesive, viscous and lipophilic properties. Furthermore, the interactions between CoQ10 and fatty acids revealed by NMR and molecular modelling experiments likely accounted for skin permeability of CoQ10. NMR data showed dose-dependent changes in proton chemical shifts in EPA and DHA. Molecular modelling revealed complex formation and large binding energies between fatty acids and CoQ10. This study advances the knowledge about bigels as drug delivery vehicles and highlights the use of NMR and molecular docking studies for the prediction of the influence of drug–excipient relationships at the molecular level.
KEY WORDSnuclear magnetic resonance molecular modelling eicosapentaenoic acid docosahexaenoic acid bigel
The authors would like to thank the Ministry of Education, Malaysia, for providing research grant ERGS/1/2013/SKK02/UKM/02/3 and Faculty of Pharmacy, Universiti Kebangsaan Malaysia, for the additional support during this study.
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Conflict of Interest
The authors declare that they have no conflict of interest.
- 4.Muta-Takada K, Terada T, Yamanishi H, Ashida Y, Inomata S, Nishiyama T, et al. Coenzyme Q10 protects against oxidative stress-induced cell death and enhances the synthesis of basement membrane components in der-mal and epidermal cells. Biofactors. 2009;35(5):435–41. https://doi.org/10.1002/biof.56.CrossRefPubMedGoogle Scholar
- 5.Gokce HE, Korkmaz E, Tanriverdi TS, Dellera E, Sandri G, Bonferonia MC, et al. A comparative evaluation of coenzyme Q10-loaded liposomes and solid lipid nanoparticles as dermal antioxidant carriers. Int J Nanomedicine. 2012;7:5109–17. https://doi.org/10.2147/IJN.S34921.PubMedPubMedCentralGoogle Scholar
- 17.Rehman K, Tan CM, Zulfakar MH. Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents. Drug Res. 2014;64:159–65.Google Scholar
- 23.Heard CM, Gallagher SJ, Harwood J, Maguire PB. The in vitro delivery of NSAIDs across skin was in proportion to the delivery of essential fatty acids in the vehicle—evidence that solutes permeate skin associated with their solvation cages? Int J Pharm. 2003;261(1):165–9. https://doi.org/10.1016/S0378-5173(03)00297-7.CrossRefPubMedGoogle Scholar
- 24.Huri DF, Shiow NF, Zulfakar MH. Fish oil-based oleogels: physicochemicals characterisation and in vitro release of betamethasone dipropionate. Int J Pharm Pharma Sci. 2013;5(3):458–67.Google Scholar
- 30.Hussain Z, Katas H, Amin MCIM, Kumolosasi E, Buang F, Sahudin S. Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: an ex vivo and in vivo study using an NC/Nga mouse model. Int J Pharm. 2013;444(1-2):109–19. https://doi.org/10.1016/j.ijpharm.2013.01.024.CrossRefPubMedGoogle Scholar
- 31.Sri P, Adimoolam S, Mahmud A. Percutaneous absorption of triacyglycerols (tags), tocols and carotenoids: comparison studies of crude and refined palm oil. Malay J Pharm Sci. 2013;11(1):33–48.Google Scholar
- 32.Al-Nuri IJ, Rahawi KY, Sharif NB. UV-derivative of spectra of co-enzyme Q0 determination of trace elements. Iraqi Natl J Chem. 2011;43:424–35.Google Scholar
- 33.Al-Faraji G, Shanshal M. Determination of ubiquinone, 10 in ten different sorts of Iraqi dates “phoenix dactylefra” at different stages of fruit maturation Jordan. J Chem. 2010;5(4):389–400.Google Scholar
- 35.Rullah K, Aluwi MFFM, Yamin BM, Abdul BMN, Wei LS, Ahmad S, et al. Inhibition of prostaglandin e2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation. Bioorg Med Chem Lett. 2014;24(16):3826–34. https://doi.org/10.1016/j.bmcl.2014.06.061.CrossRefPubMedGoogle Scholar
- 36.Rullah K, Aluwi MFFM, Yamin BM, Baharuddin MS, Ismail NH, Teruna HY, et al. Molecular characterization, biological activity, and in silico study of 2-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)-6-methoxy-4h-chromen-4-one as a novel selective cox-2 inhibitor. J Mol Struct. 2015;1081:51–61. https://doi.org/10.1016/j.molstruc.2014.10.004.CrossRefGoogle Scholar