Topical delivery of bee venom through the skin by a water-in-oil nanoemulsion

Document Type : Research Paper

Authors

1 Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

3 Tehran University of Medical Sciences

4 Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

5 Khalil Abad Health Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Bee venom (BV) contains peptides that do not pass through healthy skin due to their high molecular weight. Nanoemulsions (NEs) are capable of facilitating drug permeation through the skin.
Materials and Methods: We prepared water-in-oil (W/O) NEs containing BV with a mixture of Span 80, Tween 80, and olive oil by low energy method. Then, based on stability studies, four different NE formulations with 3, 5, 7, and 9% aqueous phase were chosen, each having different BV concentrations and characterized for their particle size, polydispersity index (PDI), viscosity, and refractive index. Afterwards, an NE preparation having 5% BV solution was used for skin permeation studies by Franz diffusion cell at three BV concentrations (i.e., 5000, 2500, and 1250 µg/ml).
Results: The results showed that by increasing the percentage of BV content (from 3 to 9 %) and surfactants (from 30 to 60 %), the size of NEs decreased while increasing BV concentration at a fixed percentage of BV content, led to increase in size and PDI. Skin permeation studies showed that after 12 h, NEs could permeate approximately 10 % of initial BV through the skin, depending on BV concentration in the NE.
Conclusion:  The data showed that NEs could be used for topical delivery of peptides of BV through the skin.

Keywords

References

1. Wiechers JW. The barrier function of the skin in relation to percutaneous absorption of drugs. Pharm Weekbl Sci. 1989;11(6):185-198.
2. Bartosova L, Bajgar J. Transdermal drug delivery in vitro using diffusion cells. Curr Med Chem. 2012;19(27):4671-4677.
3. Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol . 2008;26(11):1261.
4. López A, Llinares F, Cortell C, Herraez M. Comparative enhancer effects of Span® 20 with Tween® 20 and Azone® on the in vitro percutaneous penetration of compounds with different lipophilicities. Int J Pharm. 2000;202(1-2):133-140.
5. Yousefpoor Y, Bolouri B, Bayati M, Shakeri A, Eskandari Y. The combined effects of Aloe vera gel and silver nanoparticles on wound healing in rats. Nanomed J. 2016;3(1):57-64.
6. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997;23(1-3):3-25.
7. Abbasifard M, Yousefpoor Y, Amani A, Arababadi MK. Topical Bee Venom Nano-emulsion Ameliorates Serum Level of Endothelin-1 in Collagen-Induced Rheumatoid Arthritis Model. Bionanoscience. 2021.
8. Junqueira LA, Amaral TN, Leite Oliveira N, Prado MET, de Resende JV. Rheological behavior and stability of emulsions obtained from Pereskia aculeata Miller via different drying methods. Int J Food Prop. 2018;21(1):21-35.
9. Chime S, Kenechukwu F, Attama A. Nanoemulsions—advances in formulation, characterization and applications in drug delivery: chapter; 2014.
10. Osanloo M, Amani A, Sereshti H, Abai MR, Esmaeili F, Sedaghat MM. Preparation and optimization nanoemulsion of Tarragon (Artemisia dracunculus) essential oil as effective herbal larvicide against Anopheles stephensi. Ind Crops Prod. 2017;109:214-219.
11. Eid AM, Baie SH, Arafat O, editors. Development and stability evaluation of olive oil nanoemulsion using sucrose monoester laurate. AIP Conf Proc; 2012: AIP.
12. Kotta S, Khan AW, Pramod K, Ansari SH, Sharma RK, Ali J. Exploring oral nanoemulsions for bioavailability enhancement of poorly water-soluble drugs. Expert Opin Drug Deliv. 2012;9(5):585-598.
13. Azizi M, Esmaeili F, Partoazar A, Ejtemaei Mehr S, Amani A. Efficacy of nano-and microemulsion-based topical gels in delivery of ibuprofen: an in vivo study. J Microencapsul. 2017;34(2):195-202.
14. Wu H, Ramachandran C, Weiner ND, Roessler BJ. Topical transport of hydrophilic compounds using water-in-oil nanoemulsions. Int J Pharm. 2001;220(1-2):63-75.
15. Wu H, Ramachandran C, Bielinska AU, Kingzett K, Sun R, Weiner ND, et al. Topical transfection using plasmid DNA in a water-in-oil nanoemulsion. Int J Pharm. 2001;221(1-2):23-34.
16. Shakeel F, Ramadan W. Transdermal delivery of anticancer drug caffeine from water-in-oil nanoemulsions. Colloids Surf B Biointerfaces. 2010;75(1):356-362.
17. Abd E, Namjoshi S, Mohammed YH, Roberts MS, Grice JE. Synergistic skin penetration enhancer and nanoemulsion formulations promote the human epidermal permeation of caffeine and naproxen. J Pharm Sci. 2016;105(1):212-220.
18. Yousefpoor Y, Amani A, Divsalar A, Mousavi SE, Torbaghan YE, Emami O. Assessment of hemolytic activity of bee venom against some physicochemical factors. J Asia Pac Entomol. 2019;22(4):1129-1135.
19. Mahmoodzadeh A, Morady A, Zarrinnahad H, Bagheri KP, Ghasemi-Dehkordi P, Mahdavi M, et al. Isolating Melittin from Bee Venom and Evaluating its Effect on Proliferation of Gastric Cancer Cells. Basic & Clinical Cancer Research. 2013;5(4):26-32.
20. Fidelio GD, Maggio B, Cumar FA. Interaction of myelin basic protein, melittin and bovine serum albumin with gangliosides, sulphatide and neutral glycosphingolipids in mixed monolayers. Chem Phys Lipids. 1984;35(3):231-245.
21. Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther. 2007;115(2):246-270.
22. Oršolić N. Bee venom in cancer therapy. Cancer Metastasis Rev. 2012;31(1-2):173-194.
23. Zhang S, Liu Y, Ye Y, Wang X-R, Lin L-T, Xiao L-Y, et al. Bee venom therapy: Potential mechanisms and therapeutic applications. Toxicon. 2018;148:64-73.
24. Ali M. Studies on bee venom and its medical uses. Int J Adv Res Technol. 2012;1(2):69-83.
25. Benton AW, Morse RA, Stewart JD. Venom collection from honey bees. Science. 1963;142(3589):228-230.
26. Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M, et al. Nanoemulsion components screening and selection: a technical note. AAPS PharmSciTech. 2009;10(1):69-76.
27. Najafi-Taher R, Ghaemi B, Amani A. Delivery of adapalene using a novel topical gel based on tea tree oil nanoemulsion: Permeation, antibacterial and safety assessments. Eur J Pharm Sci. 2018;120:142-151.
28. Arzenšek D, Podgornik R, Kuzman D, editors. Dynamic light scattering and application to proteins in solutions. Seminar, Department of Physics, University of Ljubljana; 2010.
29. Shakeel F, Baboota S, Ahuja A, Ali J, Aqil M, Shafiq S. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech. 2007;8(4):191.
30. Akhtar N, Rehman M, Khan H, Rasool F, Saeed T, Murtaz G. Penetration enhancing effect of polysorbate 20 and 80 on the in vitro percutaneous absorption of lascorbic acid. Trop J Pharm Res. 2011;10(3).
31. Alkilani AZ, Hamed R, Al-Marabeh S, Kamal A, Abu-Huwaij R, Hamad I. Nanoemulsion-based film formulation for transdermal delivery of carvedilol. J Drug Deliv Sci Technol. 2018;46:122-128.
32. Khurana S, Jain N, Bedi P. Nanoemulsion based gel for transdermal delivery of meloxicam: physico-chemical, mechanistic investigation. Life sciences. 2013;92(6-7):383-392.
33. Harwansh RK, Patra KC, Pareta SK, Singh J, Rahman MA. Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin. Braz J Pharm Sci 2011;47(4):769-778.
34. Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and Transdermal Drug Delivery Systems: Current and Future Prospects. Drug Delivery. 2006;13(3):175-187.
35. Abbasi-Ghahramanloo A, Safiri S, Gholami A, Yousefpoor Y, Babazadeh S, Torkamannejad Sabzevari J. Spatio-temporal epidemiologic mapping, modeling and prediction of tuberculosis incidence rate in northeast of Iran. J Anal Res Clin Med. 2017;5(3):103-109.
36. Prausnitz MR, Elias PM, Franz TJ, Schmuth M, Tsai J-C, Menon GK, et al. Skin barrier and transdermal drug delivery. Dermatology. 2012;3:2065-2073.
37. Valizadeh A, Shirzad M, Pourmand MR, Farahmandfar M, Sereshti H, Amani A. Levofloxacin nanoemulsion gel has a powerful healing effect on infected wound in streptozotocin-induced diabetic rats. Drug Deliv Transl Res. 2021;11(1):292-304.
38. Tadros TF. Emulsion formation, stability, and rheology. Emulsion formation and stability. 2013;1:1-75.
39. Fu Z, Liu M, Xu J, Wang Q, Fan Z. Stabilization of water-in-octane nanoemulsion. Part I: Stabilized by mixed surfactant systems. Fuel. 2010;89(10):2838-2843.
40. Porras M, Solans C, González C, Martínez A, Guinart A, Gutiérrez JM. Studies of formation of W/O nano-emulsions. Colloids Surf A Physicochem Eng Asp. 2004;249(1-3):115-8.
41. Shakeel F, Baboota S, Ahuja A, Ali J, Faisal M, Shafiq S. Stability evaluation of celecoxib nanoemulsion containing Tween 80. Thai J Pharm Sci. 2008;32:4-9.
42. Kassem MG, Ahmed A-MM, Abdel-Rahman HH, Moustafa AH. Use of Span 80 and Tween 80 for blending gasoline and alcohol in spark ignition engines. Energy Reports. 2019;5:221-230.
43. Sinzato YZ, Dias NJS, Cunha FR. An experimental investigation of the interfacial tension between liquid-liquid mixtures in the presence of surfactants. Exp Therm Fluid Sci. 2017;85:370-378.
44. Jaffar AF, Akram IN, Salman AM, Al-Taai QA. Nonlinear properties of olive oil films doped with poly (methyl methacrylate), polystyrene and their blend by using z-scan technique. International Journal. 2020.
45. Alvarado H, Abrego G, Souto E, Garduño-Ramirez M, Clares B, García M, et al. Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: in vitro, ex vivo and in vivo characterization. Colloids Surf B Biointerfaces. 2015;130:40-47.
46. Khani S, Abbasi S, Keyhanfar F, Amani A. Use of artificial neural networks for analysis of the factors affecting particle size in mebudipine nanoemulsion. J Biomol Struct Dyn. 2019;37(12):3162-3167.
47. Kumar A, Kushwaha V, Sharma PK. Pharmaceutical microemulsion: Formulation, characterization and drug deliveries across skin. Int J Drug Dev Res. 2014;6(1):1-21.
48. Kaur R, Ajitha M. Transdermal delivery of fluvastatin loaded nanoemulsion gel: Preparation, characterization and in vivo anti-osteoporosis activity. Eur J Pharm Sci. 2019;136:104956.
Nanomedicine Journal
Volume 9, Issue 2
April 2022
Pages 131-137

Files

Share

How to cite

Statistics