Novel topical combo-therapeutic formulation integrating honey, neomycin and bacitracin for diabetic wound management

Authors

  • Emmanuel Uronnachi Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
  • Obinna Nwafor Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
  • Chinelo Ezejiegu Department of Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
  • Josephat Obasi Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
  • Franklin Kenechukwu Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu State, Nigeria.
  • Chukwuebuka Umeyor Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
  • Anthony Attama Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu State, Nigeria.

DOI:

https://doi.org/10.30574/gscbps.2021.17.2.0341

Keywords:

Honey, Cicatrin®, Diabetic wound, Vancomycin-oxacillin resistant Staphylococcus aureus (VORSA), Pseudomonas aeruginosa

Abstract

This study evaluated the healing effects of honey as a topical therapy for diabetic ulcers singly and in combination with bacitracin and neomycin (Cicatrin®), formulated as ointments in experimental rats.

Antimicrobial evaluation of the test agents against Vancomycin and Oxacillin resistant Staphylococcus aureus (VORSA) and Pseudomonas aeruginosa was done by the cup plate agar-diffusion technique using the Checkerboard method. Subsequently, the optimized combination was formulated into an ointment and administered as single therapy and in combination to hyperglycemic rats made diabetic by subcutaneous injection of alloxan (130 mg/kg) and inflicted with wounds. Administration was done daily on wounds for 21 days while infected wounds had the pus from them evaluated for presence of VORSA and Pseudomonas aeruginosa.

The triple combo-therapeutics formulation had improved anti-bacterial activity, in comparison with the individual formulations, with the ratio (1:9) of Cicatrin®: Honey respectively giving the best activity against VORSA. Also, the triple combo-therapeutics exhibited positive wound contraction and size reduction. Furthermore, clinical signs of infection were absent at the end of the follow-up period in the rats administered the combo-therapeutic agents while other groups of rats administered the bland ointment, and the individual agents were infected with either Pseudomonas aeruginosa or VORSA. In addition, the triple combo-therapeutics formulation exhibited good physicochemical stability throughout the treatment duration and beyond (28 days), with insignificant (p > 0.05) changes in pH and spreadability.

The triple combination therapeutics formulation showed superior effect to the singly administered agents (honey and Cicatrin®) in the management of diabetic wounds

Metrics

Metrics Loading ...

References

Akinjinmi AA, Adeyooye OA, Akingbade OA, Okerentugba PO. Prevalence of Diabetes Mellitus in Abeokuta, Ogun State. Researcher. 2014; 6: 73-5.

Bos M, Agyemang C. Prevalence and Complications of Diabetes Mellitus in Northern Africa, a Systematic Review. BMC Pub Health. 2013; 13: 387.

Ejike C, Uka NK, Nwachukwu SO. Diabetes and Prediabetes in Adult Nigerians: Prevalence, and Correlations of Blood Glucose Concentrations with Measures of Obesity. Afr J Biochem Res. 2015; 9: 55-60.

Mayega RW, Guwatudde D, Makumbi F. et al. Diabetes and Pre-Diabetes among Persons Aged 35 to 60 Years in Eastern Uganda: Prevalence and Associated Factors. PLoS ONE. 2013; 8: e72554.

Chinenye S, Young E. State of Diabetes Care in Nigeria: A Review. Nig Health Journal. 2011; 11: 101-9.

International Diabetes Foundation. Diabetes Atlas. 9th ed. Brussels: IDF. 2019.

King H, Aubert RE, Herman WH. Global Burden of Diabetes, 1995‑2025: Prevalence, Numerical Estimates, and Projections. Diabetes Care. 1998; 21: 1414‑31.

Shaw J, Sicree R, Zimmet A. Global Estimates of the Prevalence of Diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010; 87: 4-14.

Singh N, Armstrong DG, Lipsky BA. Preventing Foot Ulcers in Patients with Diabetes. JAMA. 2005; 293: 217–28.

Tong JW. Case Reports on the Use of Antimicrobial (silver impregnated) Soft Silicone Foam Dressing on Infected Diabetic Foot Ulcers Int Wound J. 2009; 6: 275-84.

Shojaiefard A, Khorgami Z, Larijani B. Septic Diabetic Foot is not necessarily an Indication for Amputation. J Foot Ankle Surg. 2008; 47: 419-23.

Dorai AA. Wound Care with Traditional, Complementary, and Alternative Medicine. Indian J Plastic Surg. 2012; 45: 418–24.

Ipek S, Satyajit DS, Lutfun N, Norazah B. Traditional Medicine for Wound Management. Hindawi Evidence-Based Complementary and Alternative Medicine. 2017.

Maver T, Kurečič M, Smrke DM, Kleinschek KS, Maver U. Plant-Derived Medicines with Potential Use in Wound Treatment. 2018.

Shedoeva A, Leavesley D, Upton Z, Fan C. Wound Healing, and the Use of Medicinal Plants. Hindawi Evidence-Based Complementary and Alternative Medicine. 2019.

Manyi-Loh CE, Clarke AM, Ndip RN. An Overview of Honey: Therapeutic Properties and Contribution in Nutrition and Human Health. Afr J Microb Res. 2011; 5: 844-52.

Alam F, Islam A, Gan SH, Khalil I. Honey: A Potential Therapeutic Agent for Managing Diabetic Wounds. Hindawi. Evidence-Based Complementary and Alternative Medicine. 2014; 16.

Farahpour, MR. Medicinal Plants in Wound Healing. Intechopen. 2019.

Song JJ, Salcido R. Use of Honey in Wound Care: An Update. Advances in Skin & Wound Care. 201; 24: 40-4.

Lusby PE, Coombes AL, Wilkinson JM. Bactericidal activity of different honeys against pathogenic bacteria. Arch Med Res. 2005; 36: 464-7.

Al-Waili NS, Akmal M, Al-Waili FS, Saloom KY, Ali A. The Antimicrobial Potential of Honey from United Arab Emirates on some Microbial Isolates. Med Sci Monitor. 2005; 11: 433-8.

Jeffery S, Henry N, Radotra I. Properties and use of a honey dressing and gel in wound management. Brit J Nurs. 2019; 28: S30-5.

Omoya FO, Akharaiyi FC. Mixture of Honey and Ginger Extract for Antibacterial Assessment on Some Clinical Isolates. Int Res J Pharm. 2012; 2: 127-32.

Imtara H, Elamine Y, Lyoussi B. Honey Antibacterial Effect Boosting Using Origanum vulgare L. Essential Oil. Hindawi Evidence-Based Complementary and Alternative Medicine. 2018; 14.

Mshelia AM, Adeshina GO, JA Onaolapo. The Antibacterial Activity of Honey and Lemon Juice against Streptococcus pneumoniae and Streptococcus pyogenes Isolates from Respiratory Tract Infections. Adv Biotech Micro. 2017; 4.

Alemseged M, Adugna S, Bayu E. Antibacterial Properties of Mixture Honey and Garlic (Allium sativum) Extracts against Respiratory Tract Infection Causing Bacteria. J Pharmacovigil. 2018; 6: 67.

Bonev B, Hooper B, Parisot, J. Principles of assessing bacterial susceptibility to antibiotics using the agar diffusion method. J Antimicrob Chemother. 2008; 61: 1295–301.

Okore VC. Pharmaceutical Microbiology: Principles of the Pharmaceutical application of antimicrobial agents. Enugu: El-Demak Ltd. 2005.

Kenechukwu FC, Attama AA, Ibezim EC, Nnamani PO, Umeyor CE, Uronnachi EM, et al. Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis. Eur J Pharm Sci. 2017; 0928-87.

Lenzen S. The mechanism of Alloxan and Streptozotocin-induced Diabetes. Diabetologia. 2008; 51: 216-26.

Isenberg HD. Editor. Clinical Microbiology Procedures Handbook. American Society for Microbiology. 2004.

Aslanzadeh J. Biochemical Profile-Based Microbial Identification Systems. In: Advanced Techniques in Diagnostic Microbiology. Springer, Boston, MA. 2006.

Rasheed A, Afifi F, Disi A. Simple Evaluation of Wound Healing Activity of a Crude Extract of Portuloca oleracea Linn. (Growing in Jordan) in Mus musculus JVI-1. J Ethnopharmacol. 2003; 88: 131-6.

Su SS, Lae KZW, Ngwe H. Isolation and Identification of Pseudomonas aeruginosa from the Clinical Soil. University of Yangon Res J. 2018; 8: 270-5.

Ryan KJ, Ray CG (editors). Sherris Medical Microbiology (4th ed.). McGraw Hill. 2004.

White R. The Benefits of Honey in Wound Management. Nurs Stand. 2005; 20(10): 57-64.

Agbagwa OE, Frank–Peterside N. Effect of Raw Commercial Honeys from Nigeria on Selected Pathogenic Bacteria. Afr J Microbiol Res. 2010; 4: 1801-3.

Sweetman S (ed). Martindale: The Complete Drug Reference. 35th edition. London: Pharmaceutical Press. 2007.

Uemura S, Yokota S, Shiraishi T, Kitagawa M, Hirayama S, Kyan R et al. Adaptive Cross-Resistance to Aminoglycoside Antibiotics in Pseudomonas aeruginosa Induced by Topical Dosage of Neomycin. Chemotherapy. 2017; 62: 121-7.

Blanchard C, Brooks L, Beckley A, Colquhoun J, Dewhurst S, Dunman PM. Neomycin Sulfate Improves the Antimicrobial Activity of Mupirocin-based Antibacterial Ointments. Antimicrob Agents Chemother. 2016; 60: 862–72.

Cutting KF. Honey and Contemporary Wound Care: An Overview. Ostomy Wound Management. 2007; 53: 49– 54.

Jull B, Cullum N, Dumville JC, Westby MJ, Deshpande S, Walker N. Honey as a topical treatment for wounds. Cochrane Database of Systematic Reviews. 2015; 3.

George NM, Cutting KF. Antibacterial Honey: In-vitro Activity against Clincal Isolates of MRSA, VRE, and other Multi-resistant Gram-negative Organisms. Wounds. 2007; 19: 231-6.

Eddy JJ, Gideonsen MD, Mack GP. Practical Considerations of using Topical Honey for Neuropathic Diabetic Foot Ulcers: A Review. Wisconsin Med J. 2008; 107: 187–90.

Furtado SC, Srinivasan B, Abraham S. Wound Healing Concepts: Contemporary Practices and Future Perspectives. Int J App Pharm. 2020; 12: 7-15.

Singh S, Sharma N. Evaluation of Wound Healing Activity of Acacia auriculiformis a. Cunn. Stem bark”. Asian J Pharm Clin Res. 2014; 7: 204-7.

Sharma KU, Singh A, Sharma U, Kumar M, Rai D, Agrahari P. Wound Healing Activity of Kigelia pinnata Bark Extract. Asian J Pharm Clin Res. 2010; 3: 74-5.

Downloads

Published

2021-11-30

How to Cite

Uronnachi, E. ., Nwafor, O. ., Ezejiegu, C. ., Obasi, J. ., Kenechukwu, F. ., Umeyor, C. ., & Attama, A. . (2021). Novel topical combo-therapeutic formulation integrating honey, neomycin and bacitracin for diabetic wound management. GSC Biological and Pharmaceutical Sciences, 17(2), 167–177. https://doi.org/10.30574/gscbps.2021.17.2.0341

Issue

Section

Original Article