Sifiso S. Makhathini1, Rahul Kalhapure1, Mahantesh Jadhav1, Ayman Y. Waddad1, Chunderika Mocktar 1, Thirumala Govender*,11Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal,... [ view full abstract ]
Sifiso S. Makhathini1, Rahul Kalhapure1, Mahantesh Jadhav1, Ayman Y. Waddad1, Chunderika Mocktar 1, Thirumala Govender*,1
1Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa
*Corresponding author.
Email address: cfiso17@gmail.com / govenderth@ukzn.ac.za
Introduction: Even though vancomycin is considered as the ultimate drug for the treatment of gram positive bacterial infections, the development of bacterial resistance has become a challenge posing a threat to public health worldwide. Targeted therapy has become a promising strategy to enhance the efficacy of antibiotics. Nano delivery systems with responsiveness to unique conditions at disease sites such as acidic conditions at infection sites can maximize targeting and drug release. The use of pH responsive novel lipids for the preparation of liposomes can improve their performance. The aim of this study is to develop novel pH-responsive liposomes encapsulated with vancomycin hydrochloride for activity against Staphylococcus aureus(SA) and methicillin-resistant Staphylococcus aureus(MRSA).
Methods: pH-sensitive lipids (Stearic, Oleic, Linoleic and Linolenic acid derivative) were synthesized and characterized using FTIR, 1H and 13C NMR. Liposomes were formulated using Dehydration-hydration method. Formulated liposomes were characterised for particle size, polydispersity index (PDI), zeta potential (Dynamic Light Scattering), entrapment efficiency (UV Spectrophotometry), in vitro drug release studies (Dialysis) and in vitro antibacterial activity (Broth dilution).
Result: All derivatives displayed superior antibacterial activity against SA and MRSA as compared to bare vancomycin. As compared to other derivatives, linoleic acid derivative (LAD) system demonstrated the best antibacterial activity and showed higher activity at pH 6.0 as compared to pH 7.4 against SA. The size and the surface charge of LAD system (drug entrapment efficiency of 38.68%) at pH 7.4 and pH 6.0 were 88.52±5.078mn and 158±1.98mn respectively and -11.8±2.99 to 1.023±0.1012 respectively. All derivatives demonstrated a sustained and enhanced release profile at pH 6.0 as compared to pH 7.4. The release behavior from all derivatives was in accordance with Korsmeyer-Peppas model(n=0.658) and release mechanism was non-fikian in both pH.
Conclusion: These results suggest that the novel pH-sensitive liposomes hold a great potential of becoming an alternative targeted intracellular delivery system for antibiotics.
