Sains Malaysiana 51(6)(2022): 1861-1873

http://doi.org/10.17576/jsm-2022-5106-21

Fusidic Acid/Tea-Tree Oil Nanoemulsions: A Potentially Safe and Effective Anti MRSA/MSSA Topical Agent for Chronic Wound Healing

(Nanoemulsi Asid Fusidik/Minyak Tea Tree: Agen Topikal Anti MRSA/MSSA yang Berpotensi Selamat dan Berkesan untuk Penyembuhan Luka Kronik)

AHMED YASEEN¹, MOWAFAQ MOHAMMED GHAREEB², DANIA F. ALSAFFAR¹, THAIGARAJAN PARUMASIVAM¹, SEOK-MING TOH¹ & AMIRAH MOHD GAZZALI^1,*

¹School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia

²Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Iraq

Diserahkan: 11 Oktober 2021/Diterima: 29 November 2021

Abstract

Fusidic acid (FA) is clinically used as an antibacterial agent for the treatment of Gram-positive bacterial infections. It interferes with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G on the ribosome. In the present work, oil-in-water nanoemulsion (NE) was developed as a carrier for the transdermal delivery of FA. Different oils, surfactants and co-surfactants were screened. The solubility of FA, the emulsifying capacity of the surfactants and phase diagrams for each oil and surfactant mix were constructed. From the analysis, eight stable NE formulations were chosen, and their physicochemical properties were further evaluated. The antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) were also evaluated, and cytotoxicity was conducted on HS-27 cell line to determine the safety of the formula. It was found that the NE produced from tea tree oil has the most optimal stability with promising antibacterial activity against MRSA as compared to a commercially available product. The safety profile of the NE was also comparable to the commercial product; thus, the formulated FA-NE is promising for clinical use.

Keywords: Fusidic acid; HS-27; MRSA; nanoemulsion; tea tree oil

Abstrak

Asid fusidik (AF) merupakan agen antibakteria yang digunakan untuk rawatan jangkitan bakteriaGram positif. Ia mengganggu proses sintesis protein dalam bakteria, secara khususnya melalui halangan translokasi faktor pemanjangan G pada ribosom. Dalam kajian ini, nanoemulsi minyak-dalam-air (NE) telah dibangunkan sebagai pembawa kepada penghantaran AF melalui laluan transdermal. Pelbagai jenis minyak, surfaktan and surfaktan bersama telah dinilai. Keterlarutan AF dalam eksipien, kapasiti pengemulsian bagi setiap surfaktan dan rajah fasa telah dibangunkan. Daripada analisis yang dijalankan, lapan formulasi NE yang stabil telah dipilih dan ciri farmakofizikal bagi setiap formulasi ini telah dinilai. Aktiviti antibakteria formulasi-formulasi NE terhadap bakteria Staphylococcus aureus rintang metisilin (MRSA) dan Staphylococcus aureus rentan metisilin (MSSA) juga telah dinilai dan kesan kesitotoksikan telah diuji pada sel HS-27 untuk menentukan keselamatan formula. NE yang dihasilkan daripada minyak tea tree ditemui mempunyai kestabilan yang paling optimum berbanding NE yang dihasilkan daripada minyak lain yang diuji, dengan aktiviti antibakteria yang baik terhadap bakteria MRSA berbanding produk komersial. Keselamatan formula NE juga adalah setara dengan produk komersial, jadi ia berpotensi untuk dibangunkan dengan lebih lanjut bagi kegunaan klinikal.

Kata kunci: Asid fusidik; HS-27; minyak tea tree; MRSA; nanoemulsi

RUJUKAN

Abolmaali, S.S., Tamaddon, A.M., Farvadi, F.S., Daneshamuz, S. & Moghimi, H. 2011. Pharmaceutical nanoemulsions and their potential topical and transdermal applications. Iranian Journal of Pharmaceutical Sciences 7(3): 139-150.

Aswathanarayan, J.B. & Vittal, R.R. 2019. Nanoemulsions and their potential applications in food industry. Frontiers in Sustainable Food Systems https://doi.org/10.3389/fsufs.2019.00095.

Azeem, A., Rizwan, M., Ahmad, F.J., Khar, R.K., Iqbal, Z. & Talegaonkar, S. 2009. Components screening and influence of surfactant and cosurfactant on nanoemulsion formation. Current Nanoscience 5(2): 220-226.

Boateng, L., Ansong, R., Owusu, W. & Steiner-Asiedu, M. 2016. Coconut oil and palm oil’s role in nutrition, health and national development: A review. Ghana Medical Journal 50(3): 189-196.

Desai, K.G.H. & Park, H. 2004. Solubility studies on valdecoxib in the presence of carriers, cosolvents, and surfactants. Drug Development Research 62(1): 41-48.

Devalapally, H., Silchenko, S., Zhou, F., McDade, J., Goloverda, G., Owen, A. & Hidalgo, I.J. 2013. Evaluation of a nanoemulsion formulation strategy for oral bioavailability enhancement of danazol in rats and dogs. Journal of Pharmaceutical Sciences 102(1): 3808.

Eleraky, N.E., Allam, A., Hassan, S.B. & Omar, M.M. 2020. Nanomedicine fight against antibacterial resistance: An overview of the recent pharmaceutical innovations. Pharmaceutics 12(2): 142.

Elfiyani, R., Amalia, A. & Pratama, S.Y. 2017. Effect of using the combination of tween 80 and ethanol on the forming and physical stability of microemulsion of eucalyptus oil and antibacterial. Journal of Young Pharmacists 9(1s): s1-s4.

El-Refai, A.A., Rabie, M.M., Ebrahem, R. & Al-Saban, W.A. 2019. Nanoemulsion of sesame seeds oil: Preparation, evaluation and stability. Asian Journal of Chemistry 31(12): 3004.

Farag, R.S., Shalaby, A.S., El‐Baroty, G.A., Ibrahim, N.A., Ali, M.A. & Hassan, E.M. 2004. Chemical and biological evaluation of the essential oils of different Melaleuca species. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 18(1): 30-35.

Fernandes, P. 2016. Fusidic acid: A bacterial elongation factor inhibitor for the oral treatment of acute and chronic staphylococcal infections. Cold Spring Harbor Perspectives in Medicine 6(1): a025437.

Frimodt-Møller, N. 2010. Fusidic acid (fusidate sodium). In Kucers’ The Use of Antibiotics. 6th ed., edited by Grayson, M.L., Crowe, S.M., McCarthy, J.S., Mills, J., Mouton, J.W., Norrby, S.R., Paterson, D.L. & Pfaller, M.A. Boca Raton: CRC Press. pp. 945-954.

Frykberg, R.G. & Banks, J. 2015. Challenges in the treatment of chronic wounds. Advance in Wound Care (New Rochelle) 4(9): 560-582.

Godtfredsen, W.O., Jahnsen, S., Lorck, H., Roholt, K. & Tybring, L. 1962. Fusidic acid: A new antibiotic. Nature 193: 987.

Gupta, A.K., Mishra, D.K. & Mahajan, S.C. 2011. Preparation and in-vitro evaluation of self-emulsifying drug delivery system of antihypertensive drug valsartan. International Journal of Pharmaceutical & Life Sciences 2(3): 633-639.

Kale, S.N. & Deore, S.L. 2016. Solubility enhancement of Nebivolol by micro emulsion technique. Journal of Young Pharmacists 8(4): 356-367.

Latif, M.A., Ibrahim, F.W., Arshad, S.A., Hui, C.K., Jufri, N.F. & Hamid, A. 2019. Cytotoxicity, proliferation and migration rate assessments of human dermal fibroblast adult cells using Zingiber zerumbet extract. Sains Malaysiana 48(1): 121-127.

Lucero, M.J., Vigo, J. & León, M.J. 1994. A study of shear and compression deformations on hydrophilic gels of tretinoin. International Journal of Pharmaceutics 106(2): 125-133.

Maddela, R., Pilli, N.R., Maddela, S., Pulipati, C.R., Polagani, S.R. & Makula, A. 2017. A novel and rapid LC-MS/MS assay for the determination of mycophenolate and mycophenolic acid in human plasma. Journal of Young Pharmacists 9(1): 106-113.

Marslin, G., Selvakesavan, R.K., Franklin, G., Sarmento, B. & Dias, A.C.P. 2015. Antimicrobial activity of cream incorporated with silver nanoparticles biosynthesized from Withania somnifera. International Journal of Nanomedicine 10: 5955-5963.

Mosmann, T. 1983. Rapid calorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65(1-2): 55-63.

Nemichand, S.K. & Laxman, S.D. 2016. Solubility enhancement of Nebivolol by micro emulsion technique. Journal of Young Pharmacists 8(4): 356-357.

Panaitescu, D.M., Ionita, E.R., Nicolae, C.A., Gabor, A.R., Ionita, M.D., Trusca, R., Lixandru, B.E., Codita, I. & Dinescu, G. 2018. Poly(3-hydroxybutyrate) modified by nanocellulose and plasma treatment for packaging applications. Polymers 10(11): 1249.

Perry, M.J., Hendricks-Gittins, A., Stacey, L.M., Adlard, M.W. & Noble, W.C. 1983. Fusidane antibiotics produced by dermatophytes. The Journal of Antibiotics 36(12): 1659-1663.

Rivero-Cruz, J.F., Granados-Pineda, J., Pedraza-Chaverri, J., Pérez-Rojas, J.M., Kumar-Passari, A., Diaz-Ruiz, G. & Rivero-Cruz, B.E. 2020. Phytochemical constituents, antioxidant, cytotoxic, and antimicrobial activities of the ethanolic extract of Mexican brown propolis. Antioxidants 9(1): 70.

Rokad, V., Nagda, C. & Nagda, D. 2014. Design and evaluation of solid self-emulsifying drug delivery system of rosuvastatin calcium. Journal of Young Pharmacists 6(3): 37-46.

Shnoudeh, A.J., Hamad, I., Abdo, R.W., Qadumii, L., Jaber, A.Y., Surchi, H.S. & Alkelany, S.Z. 2019. Chapter 15 – Synthesis, characterization, and applications of metal nanoparticles. In Biomaterials and Bionanotechnology: Advances in Pharmaceutical Product Development and Research, edited by Tekade, R.K. London: Associated Press.  p. 527.

Sugumar, S., Mukherjee, A. & Chandrasekaran, N. 2015. Eucalyptus oil nanoemulsion-impregnanted chitosan film: Antibacterial effects against a clinical pathogen, Staphylococcus aureus, in vitro. International Journal of Nanomedicine 10(Suppl 1): 67-75.

Sugumar, S., Ghosh, V., Nirmala, M.J., Mukherjee, A. & Chandrasekaran, N. 2014. Ultrasonic emulsification of eucalyptus oil nanoemulsion: Antibacterial activity against Staphylococcus aureus and wound healing activity in Wistar rats. Ultrasonics sonochemistry 21(3): 1044-1049.

Teo, S.Y., Lee, S.Y., Ong, H.L., Ong, C.L., Gan, S.N., Rathbone, M.J. & Coombes, A.G. 2015. Evaluation of biosourced alkyd nanoemulsions as drug carriers. Journal of Nanomaterials 2015: 537598.

Tubtimsri, S., Limmatvapirat, C., Limsirichaikul, S., Akkaramongkolporn, P., Inoue, Y. & Limmatvapirat, S. 2018. Fabrication and characterization of spearmint oil loaded nanoemulsions as cytotoxic agents against oral cancer cell. Asian Journal of Pharmaceutical Sciences 13(5): 425-437.

Zhu, Y., Zhang, J., Zheng, Q., Wang, M., Deng, W., Li, Q., Firempong, C.K., Wang, S., Tong, S., Xu, X. & Yu, J. 2015. In vitro and in vivo evaluation of capsaicin‐loaded microemulsion for enhanced oral bioavailability. Journal of the Science of Food and Agriculture 95(13): 2678-2685.

^*Pengarang untuk surat-menyurat; email: amirahmg@usm.my