PERTANIKA JOURNAL OF SCIENCE AND TECHNOLOGY

The study aims to formulate and optimise topical antibacterial preparation using Malaysian kelulut honey as the active ingredient and guar gum as the polymeric agent. Response surface methodology (RSM) was used to optimise the preparation. The acidity, honey concentration, and guar gum concentration were the independent variables. Meanwhile, the zone of inhibitions on Staphylococcus aureus ATCC6538 and Escherichia coli ATCC8739 were the response variables. The optimal preparation was evaluated on its physicochemical properties, viscosity, antibacterial efficacy, and stability. The antibacterial efficacy of the optimal preparation was compared to the commercial antibacterial gel (MediHoney^TM, Comvita). The optimal preparation was formulated at pH 3.5, honey concentration of 90% (w/v), and guar gum concentration of 1.5% (w/v). The inhibition zones measured on S. aureus ATCC6538 was 16.2 mm and E. coli ATCC8739 was 15.8 mm, respectively. The optimal preparation showed good physicochemical properties and effective antibacterial properties. However, the viscosity of the preparation was reduced by more than 50% during the six months of the stability study. Guar gum is a potential polymeric agent in preparing kelulut as topical preparation with effective antibacterial properties. Consideration of additional stabilising or preservative agent is recommended to overcome the reduction of viscosity over time.

• Ammer, R. M., Zaman, S., Khalid, M., Bilal, M., Erum, S., Huang, D., & Che, S. (2016). Optimization of antibacterial activity of Eucalyptus tereticornis leaf extracts against Escherichia coli through response surface methodology. Journal of Radiation Research and Applied Sciences, 9(4), 376-385. doi: https://doi.org/10.1016/j.jrras.2016.05.001

• Anitha, G., & Pandey, V. P. (2016). Review on: Statistical designs and response surface methodology (RSM) as a tool for the optimization of HPLC methods. International Journal of Pharmacy and Analytical Research, 5(4), 552-569.

• Bakar, M. F. A., Sanusi, S. B., Bakar, F. I. A., Cong, O. J., & Mian, Z. (2017). Physicochemical and antioxidant potential of raw unprocessed honey from Malaysian stingless bees. Pakistan Journal of Nutrition, 16(11), 888-894. doi: https://doi.org/10.3923/pjn.2017.888.894

• Boukraâ, L. (Ed.). (2014). Honey in traditional and modern medicine. New York, USA: Taylor & Francis Group. doi: https://doi.org/10.1201/b15608

• Brudzynski, K., & Sjaarda, C. (2014). Antibacterial compounds of Canadian honeys target bacterial cell wall inducing phenotype changes, growth inhibition and cell lysis that resemble action of ẞ-Lactam antibiotics. PLoS One, 9(9), 1-11. doi: https://doi.org/10.1371/journal.pone.0106967.g003

• Chen, M. X., Alexander, K. S., & Baki, G. (2016). Formulation and evaluation of antibacterial creams and gels containing metal ions for topical application. Journal of Pharmaceutics, 2016, 1-10. doi: https://doi.org/10.1155/2016/5754349

• Dantas, M. G. B., Reis, S. A. G., Damasceno, C. M. D., Rolim, L. A., Rolim-neto, P. J., Carvalho, F. O., … & Almeida, J. R. G. da S. (2016). Development and evaluation of stability of a gel formulation containing the monoterpene borneol. The Scientific World Journal, 2016, 1-5. doi: https://doi.org/10.1155/2016/7394685

• Dewanjee, S., Maiti, A., Majumdar, R., Majumdar, A., & Mandal, S. C. (2008). Evaluation of antimicrobial activity of hydroalcoholic extract Schima wallichii bark. Pharmacologyonline, 1, 523-528.

• Dimeski, G., Solano, C., Petroff, M. K., & Hynd, M. (2011). Centrifugation protocols: Tests to determine optimal lithium heparin and citrate plasma sample quality. Annals of Clinical Biochemistry, 48(3), 218-222. doi: https://doi.org/10.1258/acb.2010.010230

• Dluya, T. (2016). Critical review: Antioxidant properties and antibiotic mechanism of honey against infectious diseases. International Journal of Advances in Life Science and Technology, 2, 16-24. doi: https://doi.org/10.18488/journal.72/2015.2.2/72.2.16.24

• El-Kased, R. F., Amer, R. I., Attia, D., & Elmazar, M. M. (2017). Honey-based hydrogel: In vitro and comparative in vivo evaluation for burn wound healing. Scientific Reports, 7(1), 1-11. doi: https://doi.org/10.1038/s41598-017-08771-8

• Franklin, R. C., Matthew, A. W., Jeff, A., Michael, N. D., George, M. E., Mary, J. F., … & Barbara, L. Z. (2012). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Approved standard — Ninth Edition (Vol. 32). Wayne, USA. Retrieved July 20, 2020, from https://mafiadoc.com/download/methods-for-dilution-antimicrobial-susceptibility-tests-_5a19a8801723dd4f2ac359bc.html

• Gopinath, R., & Prakash, M. (2013). Antibacterial activity of three medicinal plants against clinically isolated multidrug resistant Enterococcus faecalis (MDRE). International Journal of Current Microbiology and Applied Sciences, 2(2), 6-14.

• Hemendrasinh, J. R., & Dhruti, P. M. (2015). A review on pharmaceutical gel. International Journal of Pharmaceutical Sciences, 1(1), 33-47.

• Henriques, A. F., Jenkins, R. E., & Burton, N. F. (2010). The intracellular effects of manuka honey on Staphylococcus aureus. European Journal of Clinical Microbiology & Infectious Diseases, 29(1), 45-50. doi: https://doi.org/10.1007/s10096-009-0817-2

• Henriques, A. F., Jenkins, R. E., & Burton, N. F. (2011). The effect of manuka honey on the structure of Pseudomonas aeruginosa. European Journal of Clinical Microbiology & Infectious Diseases, 30(2), 167-171. doi: https://doi.org/10.1007/s10096-010-1065-1

• Iradhati, A. H., & Jufri, M. (2017). Formulation and physical stability test of Griseofulvin microemulsion gel. International Journal of Applied Pharmaceutics, 9(1), 7-10. doi: https://doi.org/10.22159/ijap.2017.v9s1.22_27

• Irish, J., Blair, S., & Carter, D. A. (2011). The antibacterial activity of honey derived from Australian flora. PLoS One, 6(3), 1-9. doi: https://doi.org/10.1371/journal.pone.0018229

• Ismail, W. I. W. (2016). A review on beekeeping in malaysia history, importance and future direction. Journal of Sustainability Science and Management, 11(2), 70-80.

• Jain, S., Rathod, N., Nagi, R., Sur, J., Laheji, A., Gupta, N., … & Prasad, S. (2016). Antibacterial effect of aloe vera gel against oral pathogens: An in-vitro study. Journal of Clinical and Diagnostic Research, 10(11), 41-44. doi: https://doi.org/10.7860/JCDR/2016/21450.8890

• Jalil, M. A. A., Kasmuri, A. R., & Hadi, H. (2017). Stingless bee honey, the natural wound healer: A review. Skin Pharmocology and Physiology, 30(2), 66-75. doi: https://doi.org/10.1159/000458416

• Johnston, M., McBride, M., Dahiya, D., Owusu-apenten, R., & Nigam, P. S. (2018). Antibacterial activity of Manuka honey and its components: An overview. AIMS Microbiology, 4(4), 655-664. doi: https://doi.org/10.3934/microbiol.2018.4.655

• Jones, E. M., Cochrane, C. A., & Percival, S. L. (2015). The effect of pH on the extracellular matrix and biofilms. Advances in Wound Care, 4(7), 431-439. doi: https://doi.org/10.1089/wound.2014.0538

• Kaith, B. S., Sharma, R., & Kalia, S. (2015). Guar gum based biodegradable, antibacterial and electrically conductive hydrogels. International Journal of Biological Macromolecules, 75(April), 266-275. doi: https://doi.org/10.1016/j.ijbiomac.2015.01.046

• Kateel, R., Bhat, G., Baliga, S., Augustine, A. J., Ullal, S., & Adhikari, P. (2018). Antibacterial action of tropical honey on various bacteria obtained from diabetic foot ulcer. Complementary Therapies in Clinical Practice, 30(1), 29-32. doi: https://doi.org/10.1016/j.ctcp.2017.11.001

• Kim, C., Wilkins, K., Bowers, M., Wynn, C., & Ndegwa, E. (2018). Influence of pH and temperature on growth characteristics of leading foodborne pathogens in a laboratory medium and select food beverages. Austin Food Sciences, 3(1), 1-8.

• Lu, J., Turnbull, L., Burke, C. M., Liu, M., Carter, D. A., Schlothauer, R. C., … & Harry, E. J. (2014). Manuka-type honeys can eradicate biofilms produced by Staphylococcus aureus strains with different biofilm-forming abilities. Peer J, 2(326), 1-25. doi: https://doi.org/10.7717/peerj.326

• Madiha, I. Y., Rukayadi, Y., & Norhayati, H. (2017). Effects of extraction conditions on yield, total phenolic contents and antibacterial activity of methanolic Cinnamomum zeylanicum blume leaves extract. International Food Research Journal, 24, 779-786.

• Majumdar, S., Roy, S., Gupta, R., & Khatun, N. (2018). Strategy for improving skin permeation by using topical nanoparticulate gel of aloe vera and in-vivo evaluation using wistar rats. International Journal of Scientific and Research Publications, 8(2), 323-339.

• Mohd-Aspar, M. A. S., & Edros, R. Z. (2019). Antibacterial properties of kelulut, tualang and acacia honey against wound-infecting bacteria. Journal of Tropical Agricultural Science, 42(4), 1185-1208.

• Morshedi, A., & Akbarian, M. (2014). Application of response surface methodology: Design of experiments and optimization: A mini review. Indian Journal of Fundamental and Applied Life Sciences, 4(S4), 2434-2439.

• Moussa, A., Noureddine, D., Mohamed, H. S., & Abdelmelek, M. (2012). Antibacterial activity of various honey types of Algeria against Staphylococcus aureus and Streptococcus pyogenes. Asian Pacific Journal of Tropical Medicine, 5(10), 773-776. doi: https://doi.org/10.1016/S1995-7645(12)60141-2

• Mudgil, D., Barak, S., & Khatkar, B. S. (2014). Guar gum: Processing, properties and food applications - A review. Journal of Food Scientist & Technologists, 51(3), 409-418.

• Mulye, S. P., Wadkar, K. A., & Kondawar, M. S. (2014). Formulation development and evaluation of Indomethacin emulgel. Pelagia Research Library, 4(5), 31-45.

• Negut, I., Grumezescu, V., & Grumezescu, A. M. (2018). Treatment strategies for infected wounds. Molecules, 23(9), 1-23. doi: https://doi.org/10.3390/molecules23092392

• Pande, V., Patel, S., Patil, V., & Sonawane, R. (2014). Design expert assisted formulation of topical bioadhesive gel of Sertaconazole Nitrate. Advanced Pharmaceutical Bulletin, 4(2), 121-130. doi: https://doi.org/10.5681/apb.2014.019

• Panther, D. J., & Jacob, S. E. (2015). The importance of acidification in atopic eczema: An underexplored avenue for treatment. Journal of Clinical Medicine, 4(5), 970-978. doi: https://doi.org/10.3390/jcm4050970

• Peacock, S. J., & Paterson, G. K. (2015). Mechanisms of methicillin resistance in Staphylococcus aureus. Annual Review of Biochemistry, 84(1), 577-601. doi: https://doi.org/10.1146/annurev-biochem-060614-034516

• Sanchez-Maldonado, A. F., Schieber, A., & Ganzle, M. G. (2011). Structure–function relationships of the antibacterial activity of phenolic acids and their metabolism by lactic acid bacteria. Journal of Applied Microbiology, 111(5), 1176-1184. doi: https://doi.org/10.1111/j.1365-2672.2011.05141.x

• Serra, R., Grande, R., Butrico, L., Rossi, A., Francesco, U., Settimio, … & Franciscis, S. de. (2015). Chronic wound infections: The role of Pseudomonas aeruginosa and Staphylococcus aureus. Expert Review of Anti-Infective Therapy, 13(5), 605-613. doi: https://doi.org/10.1586/14787210.2015.1023291

• Shagana, J. A., & Geetha, R. (2017). Comparative analysis of antimicrobial activity of black tea, green tea and white tea extracts on Streptococcus mutans by tube dilution method. Journal of Pharmaceutical Sciences and Research, 9(9), 1581-1582.

• Shahzad, Y., Afreen, U., Shah, S. N. H., & Hussain, T. (2012). Applying response surface methodology to optimize nimesulide permeation from topical formulation. Pharmaceutical Development and Technology, 18(6), 1391-1398. doi: https://doi.org/10.3109/10837450.2012.723721

• Sharma, R., Kaith, B. S., Kalia, S., Pathania, D., Kumar, A., Sharma, N., … & Schauer, C. (2015). Biodegradable and conducting hydrogels based on Guar gum polysaccharide for antibacterial and dye removal applications. Journal of Environmental Management, 162, 37-45. doi: https://doi.org/10.1016/j.jenvman.2015.07.044

• Shekar, P., Kumar, K. S., Jabasingh, S. A., Radhakrishnan, M., & Balagurunathan, R. (2014). Optimization of medium components for antibacterial metabolite production from marine Streptomyces sp. PUA2 using response surface methodology. International Journal of Pharmacy and Pharmaceutical Sciences, 6(7), 6-11.

• Sherlock, O., Dolan, A., Athman, R., Power, A., Gethin, G., Cowman, S., & Humphreys, H. (2010). Comparison of the antimicrobial activity of Ulmo honey from Chile and Manuka honey against methicillin-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. BMC Complementary and Alternative Medicine, 10(1), 1-5. doi: https://doi.org/10.1186/1472-6882-10-47

• Singh, M. P., Nagori, B. P., Shaw, N. R., Tiwari, M., & Jhanwar, B. (2013). Formulation development & evaluation of topical gel formulations using different gelling agents and its comparison with marketed gel formulation. International Journal of Pharmaceutical Erudition, 3(3), 1-10.

• Tan, H. T., Rahman, R. A., Gan, S. H., Halim, A. S., Hassan, S. A., Sulaiman, S. A., & Kirnpal-Kaur, B. S. (2009). The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey. BMC Complementary and Alternative Medicine, 9(1), 1-8. doi: https://doi.org/10.1186/1472-6882-9-34

• Tuksitha, L., Chen, Y. S., Chen, Y., Wong, K., & Peng, C. (2018). Antioxidant and antibacterial capacity of stingless bee honey from Borneo (Sarawak). Journal of Asia-Pacific Entomology, 21(2), 563-570. doi: https://doi.org/10.1016/j.aspen.2018.03.007

• Wang, Y., Fang, X., An, F., Wang, G., & Zhang, X. (2011). Improvement of antibiotic activity of Xenorhabdus bovienii by medium optimization using response surface methodology. Microbial Cell Factories, 10(1), 1-15. doi: https://doi.org/10.1186/1475-2859-10-98

• World Health Organisation. (2018). WHO expert committee on specification for pharmaceutical preparations. Geneva, Switzerland. Retrieved July 20, 2020, from https://apps.who.int/iris/bitstream/handle/10665/272452/9789241210195-eng.pdf?ua=1

• Yaacob, M., Rajab, N. F., Shahar, S., & Sharif, R. (2018). Stingless bee honey and its potential value: A systematic review. Food Research, 2(2), 124-133. doi: https://doi.org/10.26656/fr.2017.2(2).212

• Yagoub, N. A. G. A., & Nur, A. I. M. (2013). The influence of thermal treatment on physical properties of guar gum. International Journal of Innovations in Pharmaceutical Sciences, 2(6), 26-31.

• Zhu, T., Mao, J., Cheng, Y., Liu, H., Lv, L., Ge, M., … & Lai, Y. (2019). Recent progress of polysaccharide-based hydrogel interfaces for wound healing and tissue engineering. Advanced Materials Interfaces, 6(17), 1-22. doi: https://doi.org/10.1002/admi.201900761