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dc.contributor.advisorGovender, Thirumala.
dc.creatorNawras, Osman.
dc.date.accessioned2020-04-01T07:34:38Z
dc.date.available2020-04-01T07:34:38Z
dc.date.created2017
dc.date.issued2017
dc.identifier.urihttps://researchspace.ukzn.ac.za/handle/10413/17339
dc.descriptionMaster of Pharmacy in Pharmaceutical Sciences. University of KwaZulu-Natal, Durban, 2017.en_US
dc.description.abstractTargeted delivery of antibiotics via pH-responsive nano-formulations can combat the limitations of conventional dosage forms and reduce resistance development. Identification of new lipids for the preparation of nanocarriers is required for the development of pH-responsive systems. The aims of this study were to synthesize and characterize novel fatty acid based lipids [stearic acid derived solid lipid (SASL) and oleic acid derived liquid lipid (OALL)] and to explore their potential for the preparation of vancomycin pH-responsive nanostructured lipid carriers (VCMSAOA-NLCs). Biosafe lipids were synthesized and characterized using FTIR, 1H NMR, 13CNMR, and cytotoxicity. VCM-SAOA-NLCs were prepared using hot homogenization followed by ultrasonication technique and characterized in terms of size, polydispersity index (PDI), zeta potential (ZP), surface morphology, encapsulation efficiency (EE), in vitro drug release, in silico studies, in vitro and in vivo antibacterial activity in mice as well as bacterial cell viability studies. Biosafe lipids were successfully synthesized and characterized. Spherically shaped VCM-SAOANLCs were prepared. VCM-SAOA-NLCs formulation size, PDI, and ZP were 225.9 ± 9.1 nm, 0.258 ± 0.02 and -6.69 ± 1.1 mV respectively. EE was found to be 88.7 ± 13.12 %. In silico studies confirmed that the higher EE of VCM at a solid lipid to liquid lipid ratio of 2:1 (1603.991 kcal/mol) than 1:1 (1367.44 kcal/mol) was due to the higher affinity of VCM with the solid lipid than the liquid lipid. In vitro drug release studies revealed that VCM-SAOA-NLCs had pHsensitive sustained drug release. In vitro antibacterial activity against methicillin-susceptible and resistant Staphylococcus aureus revealed that VCM-SAOA-NLCs had superior antibacterial activity compared to bare VCM against both bacterial strains at both pH conditions. Moreover, at pH 6 VCM-SAOA-NLCs activity was four times and two times better against SA and MRSA respectively than at pH 7.4. MRSA bacterial cell viability study showed enhanced uptake and antibacterial activity of VCM-SAOA-NLCs compared to bare VCM. Furthermore, the in vivo study revealed that MRSA CFU load in mice skin treated with VCM-SAOA-NLCs was 37-fold lower than bare VCM (P < 0.05). Therefore, this novel pH-responsive NLCs may serve as a promising nanocarrier for enhancing antibiotic delivery and activity.en_US
dc.language.isoenen_US
dc.subject.otherNanocarriers.en_US
dc.subject.otherBiosafe lipids.en_US
dc.subject.otherNanostructured lipid carriers.en_US
dc.subject.otherVancomycin activity.en_US
dc.subject.otherAntibacterial activity.en_US
dc.subject.otherMethicillin-resistant Staphylococcus aureus.en_US
dc.subject.otherFatty acid.en_US
dc.titleNovel fatty acid based pH-responsive nanostructured lipid carriers for enhancing vancomycin activity.en_US
dc.typeThesisen_US


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