Formulation of pH responsive multilamellar vesicles for targeted delivery of hydrophilic antibiotics
Fight against antimicrobial resistance calls for innovative strategies that can target infection sites and enhance activity of antibiotics. Herein is a pH responsive multilamellar vesicles (MLVs) for targeting bacterial infection sites. The vancomycin (VCM) loaded MLVs had 62.25 ± 8.7 nm, 0.15 ± 0.01 and -5.55 ± 2.76 mV size, PDI and zeta potential, respectively at pH 7.4. The MLVs had a negative ZP at pH 7.4 that switched to a positive charge and faster release of the drug at acidic pH.
Highlights
pH-responsive Vancomycin loaded multilamellar vesicles (MLVs) were formulated.
The in vitro drug profile results demonstrated a faster vancomycin release from the MLVs at pH 6.0 compared to pH 7.4.
Enhanced in vitro antibacterial activity against MRSA by MLVs when compared to bare vancomycin.
Elimination of MRSA biofilms using the MLVs when compared to biofilms treated with bare vancomycin.
Enhanced in vivo antimicrobial activity of the MLVs against MRSA when compared to bare vancomycin in a mice skin infection model.
The encapsulation efficiency was found to be 46.34 ± 3.88 %. In silico studies of the lipids, interaction suggested an energetically stable system. Studies to determine the minimum inhibitory concentration studies (MIC) showed the MLVs had 2-times and 8-times MIC against Staphylococcus aureus (SA) and Methicillin resistance SA respectively at physiological pH. While at pH 6.0 there was 8 times reduction in MICs for the formulation against SA and MRSA in comparison to the bare drug. Fluorescence-activated Cell Sorting (FACS) studies demonstrated that even with 8-times lower MIC, MLVs had a similar elimination ability of MRSA cells when compared to the bare drug. Fluorescence microscopy showed MLVs had the ability to clear biofilms while the bare drug could not.
Mice skin infection models studies showed that the colony finding units (CFUs) of MRSA recovered from groups treated with MLVs was 4,050 and 525-fold lower than the untreated and bare VCM treated groups, respectively. This study demonstrated pH-responsive multilamellar vesicles as effective system for targeting and enhancing antibacterial agents.
Article information: Calvin A. Omolo, Daniel Hassan, Nikita Devnarain, Yajna Jaglal, Chunderika Mocktar, Rahul S. Kalhapure, Mahantesh Jadhav, Thirumala Govender. Formulation of pH responsive multilamellar vesicles for targeted delivery of hydrophilic antibiotics, Colloids and Surfaces B: Biointerfaces, Volume 207, 2021. https://doi.org/10.1016/j.colsurfb.2021.112043.