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

Rahul S Kalhapure; Dhiraj R Sikwal; Sanjeev Rambharose; Chunderika Mocktar; Sanil Singh; Linda Bester; Jung Kwon Oh; Jwala Renukuntla; Thirumala Govender

doi:10.1016/j.nano.2017.04.010

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

Nanomedicine. 2017 Aug;13(6):2067-2077. doi: 10.1016/j.nano.2017.04.010. Epub 2017 Apr 18.

Authors

Rahul S Kalhapure¹, Dhiraj R Sikwal², Sanjeev Rambharose², Chunderika Mocktar², Sanil Singh³, Linda Bester³, Jung Kwon Oh⁴, Jwala Renukuntla⁵, Thirumala Govender⁶

Affiliations

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.

PMID: 28434930
DOI: 10.1016/j.nano.2017.04.010

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.

Keywords: Methicillin-resistant S. aureus; Solid lipid nanoparticles; Targeted delivery; Vancomycin; pH-responsive.

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology*
Cell Survival / drug effects
Drug Carriers
Humans
Hydrogen-Ion Concentration
Inflammation / drug therapy
Inflammation / microbiology
Lipids / chemistry*
Methicillin-Resistant Staphylococcus aureus / drug effects*
Mice
Mice, Inbred BALB C
Nanoparticles / administration & dosage
Nanoparticles / chemistry*
Neoplasms / drug therapy
Skin / drug effects
Staphylococcal Infections / drug therapy*
Staphylococcal Infections / microbiology
Tumor Cells, Cultured
Vancomycin / pharmacology*

Substances

Anti-Bacterial Agents
Drug Carriers
Lipids
Vancomycin