1 Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: kalhapure@ukzn.ac.za.
2 Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
3 Biomedical Resource Unit, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.
4 Department of Chemistry and Biochemistry, Concordia University, Montreal, Quebec, Canada.
5 School of Pharmacy, The University of Texas at El Paso, El Paso, Texas, USA.
6 Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: govenderth@ukzn.ac.za.

Enhancing targeted antibiotic therapy via pH responsive solid lipid nanoparticles from an acid cleavable lipid.

Nanomedicine. 2017 Aug;13(6):2067-2077

Authors: Kalhapure RS, Sikwal DR, Rambharose S, Mocktar C, Singh S, Bester L, Oh JK, Renukuntla J, Govender T

Abstract

An acid cleavable lipid (SA-3M) was synthesized and used to develop pH-responsive solid lipid nanoparticles (SLNs) to deliver vancomycin base (VM-FB) to acidic infection sites. The size, polydispersity index and zeta potential of VM-FB_SA-3M_SLNs were 132.9±9.1nm, 0.159±0.01 and -26±4.4mV respectively, with 57.80±1.1% encapsulation efficiency. VM-FB release was significantly faster at pH6.5 than pH7.4. In vitro antibacterial activity against methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) revealed that SLNs had enhanced activity at pH6.5 than pH7.4. In vivo study showed that the amount of MRSA remaining in the skin of VM-FB_SA-3M_SLNs treated mice was approximately 22-fold lower than VM-FB treated mice. Histological investigations revealed that signs of inflammation in the skin treated with VM-FB_SA-3M_SLNs were minimal. In conclusion, this study confirmed that SA-3M can form pH-responsive SLNs capable of releasing antibiotic specifically at acidic infection sites.

PMID: 28434930 [PubMed - indexed for MEDLINE]