Optimization of Olive Oil-Based Nanoemulsion Preparation for Intravenous Drug Delivery

Abstract

A seven-factor Box-Behnken design was used for the optimized development of an olive oil-based nanoemulsion (NE) intended for intravenous drug delivery. The independent variables of olive oil concentration, tween 80 concentration, span 80 concentration, rate of adding of oil in aqueous phase, homogenization speed, homogenization time, and preparation temperature, were used as inputs of the factorial design. The response variables were mean droplet diameter, zeta potential (ZP), and polydispersity index (PDI). A quadratic, linear and 2FI model was established to predict the responses based on the multivariate model developed. The obtained experimental responses were in good agreement with predicted values from expert design, showing residual standard error (RSE) less than 10 %. TEM revealed that the optimized nanoemulsions were almost spherical with mean diameter about 40 nm. The developed formulation showed only about 4.6% of hemolysis and was safe for intravenous delivery. As well, the other in vitro characterization of the optimal nanoemulsion such as viscosity, percent transmittance, physical stability, and solubility study revealed it to be promising as an intravenous drug delivery system.

Key words

Nanoemulsion - Box-Behnken Design - Intravenous Drug Delivery System - Optimization

• References

• 1 Li W, Li Z, Weil L. et al. Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo. Drug research 2018; 68: 205-212
• 2 Karami Z, Hamidi M. Cubosomes: Remarkable drug delivery potential. Drug discovery today 2016; 21: 789-801
• 3 Yang S. Preparation, in vitro Characterization and Pharmacokinetic Study of Coenzyme Q10 Long-Circulating Liposomes. Drug research 2017
• 4 Karami Z, Sadighian S, Rostamizadeh K. et al. Naproxen conjugated mPEG–PCL micelles for dual triggered drug delivery. Materials Science and Engineering: C. 2016; 61: 665-673
• 5
• 6 Hörmann K, Zimmer A. Drug delivery and drug targeting with parenteral lipid nanoemulsions—A review. Journal of Controlled Release. 2016; 223: 85-98
• 7 Sutradhar KB, Amin M. Nanoemulsions: Increasing possibilities in drug delivery. European Journal of Nanomedicine 2013; 5: 97-110
• 8 Tamilvanan S. Formulation of multifunctional oil-in-water nanosized emulsions for active and passive targeting of drugs to otherwise inaccessible internal organs of the human body. International journal of pharmaceutics 2009; 381: 62-76
• 9 Tripoli E, Giammanco M, Tabacchi G. et al. The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutrition research reviews 2005; 18: 98-112
• 10 Ueda CT, Lemaire M, Gsell G. et al. Intestinal lymphatic absorption of cyclosporin A following oral administration in an olive oil solution in rats. Biopharmaceutics & drug disposition 1983; 4: 113-124
• 11 Singh VK, Ramesh S, Pal K. et al. Olive oil based novel thermo-reversible emulsion hydrogels for controlled delivery applications. Journal of Materials Science: Materials in Medicine 2014; 25: 703-721
• 12 Alonso A, Martínez-González MÁ. Olive oil consumption and reduced incidence of hypertension: The SUN study. Lipids 2004; 39: 1233-1238
• 13 López-Miranda J, Pérez-Martínez P, Pérez-Jiménez F. Health benefits of monounsaturated fatty acids Elsevier (2006)
• 14 Nasr M, Nawaz S, Elhissi A. Amphotericin B lipid nanoemulsion aerosols for targeting peripheral respiratory airways via nebulization. International Journal of Pharmaceutics 2012; 436: 611-616
• 15 Nanjwade BK, Varia PJ, Vikrant T. Development and evaluation of nanoemulsion of Repaglinide. Nanotechnol. Nanomed 2013; 1: 1-8
• 16 Hua Y, Li W, Cheng Z et al. Solidification of Nanostructured Lipid Carriers Loaded Testosterone Undecanoate: In Vivo and In Vitro Study. Drug research 2018
• 17 Liu W, Sun D, Li C. et al. Formation and stability of paraffin oil-in-water nano-emulsions prepared by the emulsion inversion point method. Journal of colloid and interface science 2006; 303: 557-563
• 18 Aditya NP, Aditya S, Yang H. et al. Co-delivery of hydrophobic curcumin and hydrophilic catechin by a water-in-oil-in-water double emulsion. Food chemistry 2015; 173: 7-13
• 19 Kanimozhi V, Sridhar S. Optimization of process parameters using Box–Behnken Design towards uptake of acid orange 10 using casuarina charcoal. Adv. Biotechnol 2013; 12: 5-9
• 20 Krupa AND, Abigail MEA, Santhosh C. et al. Optimization of process parameters for the microbial synthesis of silver nanoparticles using 3-level Box–Behnken Design. Ecological Engineering. 2016; 87: 168-174
• 21 Singh U, Meher JG, Raval K. et al. Nanoemulsion: Concepts, development and applications in drug delivery. Journal of Controlled Release. 2017; 252: 28-49
• 22 Peng LC, Liu CH, Kwan CC. et al. Optimization of water-in-oil nanoemulsions by mixed surfactants. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2010; 370: 136-142
• 23 Saberi AH, Fang Y, McClements DJ. Fabrication of vitamin E-enriched nanoemulsions: factors affecting particle size using spontaneous emulsification. Journal of colloid and interface science 2013; 391: 95-102
• 24 Azeem A, Rizwan M, Ahmad FJ. et al. Nanoemulsion components screening and selection: A technical note. Aaps Pharmscitech. 2009; 10: 69-76
• 25 Araújo FA, Kelmann RG, Araújo BV. et al. Development and characterization of parenteral nanoemulsions containing thalidomide. European Journal of Pharmaceutical Sciences. 2011; 42: 238-245
• 26 Sintov AC, Shapiro L. New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo. Journal of Controlled Release. 2004; 95: 173-183