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Mol Pharm. 2018 Aug 6;15(8):3512-3526. doi: 10.1021/acs.molpharmaceut.8b00505. Epub 2018 Jul 13.

Formulation and Molecular Dynamics Simulations of a Fusidic Acid Nanosuspension for Simultaneously Enhancing Solubility and Antibacterial Activity.

Author information

1
Discipline of Pharmaceutical Sciences , College of Health Sciences, University of KwaZulu-Natal , Private Bag , X54001 Durban , South Africa.
2
School of Pharmacy , The University of Texas at El Paso , 500 W. University Avenue , El Paso , Texas 79968 , United States.
3
Division of Emergency Medicine, Department of Surgery , University of Cape Town , Cape Town 7700 , South Africa.

Abstract

The aim of the present study was to formulate a nanosuspension (FA-NS) of fusidic acid (FA) to enhance its aqueous solubility and antibacterial activity. The nanosuspension was characterized using various in vitro, in silico, and in vivo techniques. The size, polydispersity index, and zeta potential of the optimized FA-NS were 265 ± 2.25 nm, 0.158 ± 0.026, and -16.9 ± 0.794 mV, respectively. The molecular dynamics simulation of FA and Poloxamer-188 showed an interaction and binding energy of -74.42 kJ/mol and -49.764 ± 1.298 kJ/mol, respectively, with van der Waals interactions playing a major role in the spontaneous binding. There was an 8-fold increase in the solubility of FA in a nanosuspension compared to the bare drug. The MTT assays showed a cell viability of 75-100% confirming the nontoxic nature of FA-NS. In vitro antibacterial activity revealed a 16- and 18-fold enhanced activity against Staphylococcus aureus (SA) and methicillin-resistant SA (MRSA), respectively, when compared to bare FA. Flowcytometry showed that MRSA cells treated with FA-NS had almost twice the percentage of dead bacteria in the population, despite having an 8-fold lower MIC in comparison to the bare drug. The in vivo skin-infected mice showed a 76-fold reduction in the MRSA load for the FA-NS treated group compared to that of the bare FA. These results show that the nanosuspension of antibiotics can enhance their solubility and antibacterial activity simultaneously.

KEYWORDS:

MRSA; enhanced antibacterial activity; improved solubility; molecular dynamics; nanosuspension

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