Novel fatty acid-based pH-responsive nanostructured lipid carriers for enhancing antibacterial delivery

• Published in: Journal of drug delivery science and technology Vol. 53; p. 101125
• Main Authors: Osman, Nawras, Omolo, Calvin A., Gannimani, Ramesh, Waddad, Ayman Y., Rambharose, Sanjeev, Mocktar, Chunderika, Singh, Sanil, Parboosing, Raveen, Govender, Thirumala
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2019
• Subjects: Methicillin-resistant; Nanostructured lipid carriers; pH-responsive; Staphylococcus aureus (MRSA); Vancomycin; Nanostructured lipid carriers; Vancomycin; Staphylococcus aureus (MRSA); Methicillin-resistant; pH-responsive
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2019.101125

The present study is aimed at the employment of novel fatty acid derived lipids for the preparation of pH-responsive nanostructured lipid carriers (NLCs) for vancomycin (VCM) intravenous delivery against resistant and sensitive Staphylococcus aureus bacteria. Two branched lipids [stearic ‏acid derived solid lipid and oleic acid derived liquid lipid‏] were synthesized, characterized and used to fabricate NLCs by hot homogenization technique. Particle size, ‏polydispersity index, zeta potential and encapsulation efficiency were 225.2 ± 9.1 nm, 0.258 ± 0.02, −9.2 ± 2.7 mV and 88.7 ± 13.12%, respectively. An understanding of drug encapsulation efficiencies and formation of the NLCs were supported by in silico studies. In vitro antibacterial activity revealed ‏that‏ VCM loaded-NLCs had higher activity against methicillin-susceptible and resistant Staphylococcus aureus than the bare VCM. Cell viability study showed that NLCs had 2.5-fold better killing percentage than the bare drug at similar concentrations. Furthermore, the in vivo efficacy of VCM loaded-NLCs was assessed in a mouse model of MRSA skin infection. MRSA CFU load of the skin treated with NLCs was 37-fold lower than bare VCM (p < 0.05). This novel pH-responsive NLCs may, therefore, show potential for efficient and enhanced antibiotic delivery. [Display omitted]