NANOEMULSION GEL OF NUTRACEUTICAL CO-ENZYME Q10 AS AN ALTERNATIVE TO CONVENTIONAL TOPICAL DELIVERY SYSTEM TO ENHANCE SKIN PERMEABILITY AND ANTI-WRINKLE EFFICIENCY
Keywords:Coenzyme Q10, Nanoemulsion gel, Topical delivery, Skin wrinkles, Permeability
Objective: The object of our investigation was to develop and characterize nanoemulsion gel (NEG) as transdermal delivery systems for the poorly water soluble drug, Co-enzyme Q10 (CoQ10), to improve its solubility and skin permeability and thus improving its anti-wrinkle efficiency.
Methods: An optimized nanoemulsion (NE) formula was chosen according to its particle size and stability and converted into nanoemulsion gel using different gelling agents, including; carbopol 934 (1%), xanthan gum (2%) and sodium carboxymethyl cellulose(NaCMC) (2%). Drug loaded nanoemulsion gels were characterized for particle size, zeta potential, viscosity and rheological behavior, conductivity, spreadability, drug content and permeation studies using Franz diffusion cell.
Results: NEG containing 10% w/v isopropyl myristate (IPM) as oil, 60% w/v tween 80 and transcutol HP as surfactant/co-surfactant mixture (S/CoS), 30%w/v water, 2%w/v drug, and 1% w/v carbopol 934 as gelling gent was concluded as an optimized NEG formula. It exhibited pH, viscosity, drug content, particle size, zeta potential, polydispersity index(PDI) and spreadability, as 5.4Â±0.011, 27588Â±2034.34 cps,101.51Â±0.93%,120.5Â±1.19 nm,-29.8Â±1.46, 0.273 and 6.16Â±0.28 cm, respectively. Also, it showed significantly higher cumulative amount of drug permeated through dialysis membrane (281.71Â±0.97Î¼g/cm2) and through rat skin (20.73Â±2.5 Î¼g/cm2) than the other formulae and marketed formulation (P<0.001). In addition, its permeability parameters like drug flux (Jss), enhancement ratio (Er) and permeability coefficient (Kp) exhibited the highest values; 12.79Âµg/cm2/h, 95.92Ã—10-4 cm2/h and 57.35, respectively for in vitro permeation study and 0.968Âµg/cm2/h, 7.26Ã—10-4 cm2/h and 1.183, respectively for ex-vivo permeation study.
Further histopathological evaluation test showed that CoQ10 NEG has a good anti-wrinkle efficacy compared to the conventional topical dosage form.
Conclusion: These results judged NEG to be a promising alternative carrier for topical delivery of CoQ10 to enhance its solubility, skin permeability and thus anti-wrinkle efficiency.
Adnan A, Sushama T, Lalit MN, Farhan JA, Roop KK, Zeenat I. Oil based nanocarrier system for transdermal delivery of ropinirole: a mechanistic, pharmacokinetic and biochemical investigation. Int J Pharm 2012;422:436-44.
Sunil KY, Manoj KM, Anupamaa T, Ashutosh S. Emulgel: a new approach for enhanced topical drug delivery. Int J Curr Pharm Res 2017;9:15-9.
Panwar AS, Upadhyay N, Bairagi M. Emulgel: a review. Asian J Pharm Life Sci 2011;1:333-4.
Rania H, Marwa, Tamadur A, Suhair S, Ola T. Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies. Pharm Dev Technol 2015:1-10. Doi:10.3109/10837450.2015.1086372
Baboota S, Shakeel F, Ahuja A. Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib. Acta Pharm 2007;57:315â€“32.
Koteswari P, Krishna SR, Reddy VP, Narasu LM. Formulation and preparation of felodipine nanoemulsions. Asian J Pharm Clin Res 2011;4:116-7.
Gupta PV, Pandit JK, Narain PJ. Design, optimization and evaluation of nanoemulsion formulations by ultrasonication as vehicle for transdermal delivery of diclofenacdiethylamine. Pharmbit 2011;23:26â€“39.
Shah P, Bhalodia D, Shelat P. Nanoemulsion: a pharmaceutical review. Sys Rev Pharm 2010;1:24â€“32.
Singh M, Jain S. Nanoemulsion for skin targeting: present status and future prospects. Drug Delivery Lett 2011;1:159â€“70.
Ambade K, Jadhav SL, Gambhire MN, Kurmi SD, Kadam VJ, Jadhav KR. Formulation and evaluation of flurbiprofen microemulsion, Curr Drug Delivery 2008;5:32â€“41.
Shokri J, Azarmi S, Fasihi Z. Effects of various penetration enhancers on percutaneous absorption of piroxicam from emulgels. Res Pharm Sci 2012;7:225â€“34.
Veerawat T, Eliana BS, Varaporn BJ, Rainer HM. Cetyl palmitate-based NLC for topical delivery of coenzyme Q10â€“development, physicochemical characterization and in vitro release studies. Eur J Pharm Biopharm 2007;67:141â€“8.
Joe V, Sunil A. Comparative topical absorption and antioxidant effectiveness of two forms of coenzyme Q10 after a single dose and after long-term supplementation in the skin of young and middle-aged subjects. IFSCC Magazine 2005;8:1-6.
Ljiljana D, Marija P. The influence of co-surfactants and oils on the formation of pharmaceutical microemulsions based on PEG-8 caprylic| capric glycerides. Int J Pharm 2008;352:231-9.
Singh BP, Kumar B, Jain SK. Development and characterization of a nanoemulsion gel formulation for transdermal delivery of carvedilol. Int J Drug Devand Res 2012;4:151-6.
Varaporn BJ, Veerawat T, Eliana BS, Prapaporn B, Rainer HM. Q10-loaded NLC versus nanoemulsions: stability, rheology and in vitro skin permeation. Int J Pharm 2009;377:207â€“14.
Sheela AY, Sushilkumar SP. Formulation, in vitro and in vivo evaluation of nanoemulsion gel for transdermal drug delivery of nimodipine. Asian J Pharm Clin Res 2015;8:119-24.
Abeer K, Soha I. Formulation and evaluation of oxiconazole nitrate mucoadhesive nanoemulsion based gel for treatment of fungal vaginal infection. Int J Pharm Pharm Sci 2016;8:33-40.
Sajid AMD, Sarfaraz AMD, Nawazish A, Syed A, Shah Q, Intakhab AMD. Formulation, characterization and in vivo assessment of topical nanoemulsion of betamethasone valerate for psoriasis and dermatose. Int J Pharm 2013;3:186-99.
Mahesh B, Vasanth KP, Gowda DV, Atul S, Raghundan HV, Chetan SG. Enhanced permeability of cyclosporine from a transdermally applied nanoemulgel. Der Pharm Sinica 2015;6:69-7.
Elnaggar YSR, Talaat SM, Bahey-El-Din M, Abdallah OY. Novel lecithin-integrated liquid crystalline nanogels for enhanced cutaneous targeting of terconazole: development, in vitro and in vivo studies. Int J Nanomed 2016;11:5531-47.
Doaa AH, Dalia AE, Sally AA, Mohamed AE. Formulation and evaluation of fluconazole topical gel. Int J Pharm Pharm Sci 2012;4:176-83.
Zhao YI, Changguang W, Albert HL, Ren K, Tao G, Zhirong Z. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of zedoary essential oil: formulation and bioavaliability studies. Int J Pharm 2010;383:170-7.
Sripriya VR, Payal A, Jun S. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs II. In vitro transport study. Int J Pharm 2008;362:10-5.
Songkro S, Purwo Y, Becket G, Rades T. Investigation of newborn pig skin as an in vitro animal model for transdermal drug delivery. STP Pharma Sci 2003;13:133â€“9.
Junyaprasert VB, Boonme P, Songkro S, Krauel K, RadesT. Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o brij97 based microemulsions. J Pharm Pharm Sci 2007;10:288â€“9.
Sandig AG, Calpena CAC, Fernandez CF, Martin VMJ, Clares NB. Transdermal delivery of imipramine and doxepin from newly oil-in-water nanoemulsions for an analgesic and anti-allodynic activity: development, characterization and in vivo evaluation. Colloids Surf B 2013;103:558â€“65.
Baboota S, Faiyaz S, Alka A, Javed A, Sheikh S. Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib. Acta Pharm 2007;57:315â€“32.
Duraivel S, Asma SS, Rabbani BS, Eesaf PS, Jilani S. Formulation and evaluation of anti-wrinkle activity of cream and nanoemulsion of moringaoleifera seed oil. IOSR J Pharm Biol Sci 2014;9:58-73.
Banchroft JD, Stevens A, Turner DR. Theory and practice of histological techniques. Fourth Ed. Churchil Livingstone, 1996, New York, London, San Francisco, Tokyo. 4th ed. Ch 6; 1996. p. 99-112.
Khurana S, Jain NK, Bedi PMS. Nanoemulsion based gel for transdermal delivery of meloxicam: physico-chemical, mechanistic investigation. Life Sci 2013;92:383â€“92.
Marta PA, Renata PR, Solange BF. Rheological behavior of semisolid formulations containing nanostructured systems. Nanocosmetics and nanomedicine; 2011. p. 37-45.
Alina O, Cristina DP, Mihaela VG, Lidia MP, Lucian I. Rheological study of a liposomal hydrogel based on carbopol. Romanian Biol Lett 2011;16:47-54.
Kesavan B, Jayaraman A, Velayutham R, Vobalaboina V, Yamsani MR. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies. Lipids Health Disease 2009;8:1-15.
Carla V, LuÄ±Â´s A, Filipe EA, Joao JS, Alberto ACC. Design of a dual nanostructured lipid carrier formulation based on physicochemical, rheological, and mechanical properties. J Nanopart Res 2013;15:1993.
Hamed M, Chin PT. Effect of various hydrocolloids on physicochemical characteristics of orange beverages emulsion. J Food Agric Environ 2010;8:308-13.
Leila A, Shekoufeh B, Hamed H. The impact of variables on particle size of solid lipid nanoparticles and nanostructured lipid carriers; a comparative literature review. Adv Pharm Bull 2016;6:143â€“51.
Saharudin SH, Ahmad Z, Basri M. Role of xanthan gum on physicochemical and rheological properties of rice bran oil emulsion. Int Food Res J 2016;23:1361-6.
Pensak J, Warintorn R. Carbopol-guar gum gel as a vehicle for topical gel formulation of pectin beads loaded with rutin. Asian J Pharm Clin Res 2014;7:231-6.
Cheng LN, Mahiran B, Minaketan T, Roghayeh AK, Emilia A. Physicochemical characterization and thermodynamic studies of nanoemulsion-based transdermal delivery system for fullerene. Sci World J 2014:1-12. http://dx.doi.org/10.1155/2014/219035
Mohd S, Asmal R, Siti R, Azizan A, Nor SM. Biopolymer electrolyte based on derivatives of cellulose from kenaf bast fiber. Polymers 2014;6:2371-85.
Hanan R, Randa T. Development and characterization of sponge-like acyclovir ocular minitablets. Drug Delivery 2011;18:38-45.
Sareen R, Kumar S, Gupta GD. Meloxicam carbopol-based gels: characterization and evaluation. Curr Drug Delivery 2011;8:407â€“15.
Gaikwad VL, Yadav VD, Dhavale RP, Choudhari PB, Jadhav SD. Effect of carbopol 934 and 940 on fluconazole release from topical gel formulation: a factorial approach. Curr Pharma Res 2012;2:487â€“93.
Bhalekar MR, Madgulkar AR, Kadam GJ. Evaluation of gelling agents for Clindamycin phosphate gel. World J Pharm Pharm Sci 2015;4:2022â€“33.
Vinod KR, Santosh V, Sandhya S, David B, Otilia B, Yamsani MR. Comparative study of mucoadhesive polymers carbopol 974p and sodium carboxymethyl cellulose for single unit dosage of imatinib mesylate. Malaysian J Pharm Sci 2012;10:61â€“77.
Gautam S, Abhishek S, Nilesh Y, Ranendra NS. Study the effect of formulation variables on drug release from hydrophilic matrix tablets of milnacipran and prediction of in vivo plasma profile. Pharm Dev Technol 2013;13:1â€“9.
Elahe T, Zahra JA, Seyed AM. Development and in vitro evaluation of a contraceptive vagino-adhesive propranolol hydrochloride gel. Iran J Pharm Res 2012;11:13â€“26.
Siang YL, Yeong YP, Boon KK, Wei EK, Cai TT, Siew YT. Lipid-based delivery system for topical phenytoin. J Appl Pharm Sci 2016;6:14-20.
Yin Z, Wu-Qing O, Yun-Peng W, Shahid FS, Chao-Shuang H, Bo-Zhen W, et al. Effects of carbopolÂ® 934 proportion on nanoemulsion gel for topical and transdermal drug delivery: a skin permeation study. Int J Nanomed 2016;11:5971â€“87.
Gaur PK, Mishra S, Purohit S, Dave K. Transdermal drug delivery system: a review. Asian J Pharm Clin Res 2009;2:14-20.
Marks R, Knight A, Laidler P. Atlas of skin pathology. Curr Histopathol 2015;11:9.
Jie S, Christopher RS. Benign versus malignant parakeratosis: a nuclear morphometry study. Modern Pathol 2010;23:799â€“803.
Chung JH, Seo JY, Choi HR, Lee MK, Youn CS, Rhie G, et al. Modulation of skin collagen metabolism in aged and photoaged human skin in vivo. J Invest Dermatol 2001;117:1218â€“24.
Zhang M, Dang L, Guo F, Wang X, Zhao W, Zhao R. Coenzyme Q10 enhances dermal elastin expression, inhibits IL-1a production and melanin synthesis in vitro. Int J Cosmet Sci 2012;34:273â€“9.