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

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.

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

“…An increase was observed in the concentration above ration 1:1; the particles sizes and PDI increased. It has been reported before that the stabilizing effect of surfactant decreases at high concentrations as the surfactant molecules tend to aggregate in to micelles rather than associating with lipidic molecules [ 52 , 63 ]. The optimized drug-loaded quatsomes (VCM-StBAclm-Qt 1 ) had MHD, and PDI of 122.9 ± 3.78 nm and 0.169 ± 0.02, respectively, at physiological pH 7.4 ( Figure 1 B).…”

Accelerated Aqueous Solubility and Antibacterial Activity of Cefuroxime Axetil Using Microcrystalline Cellulose as Carrier

“…Khan et al (2016) reported that, cefixime nanoparticles exhibited better antibacterial activity than pure cefixime against S. aureus and E. coli by agar well diffusion method [27]. Omolo et al (2018) demonstrated that antibacterial activities of different nanosuspension formulations of fusidic acid delivered through poloxamer 188 were found better as compared to pure fucidic acid [28]. Further, it was revealed that both in-vitro and in-vivo test of CA amorphous ultrafine particles by high gravity anti-solvent precipitation (HGAP) technique possessed better dissolution rate and stronger antibacterial activity by agar dilution method against S. aureus and E. coli [29].…”

Nano/Microparticles Encapsulation Via Covalent Drug Conjugation

“…Micro-and nano-carrier systems are among the approaches that have been successfully utilized for encapsulation of various types of drugs such as peptides, proteins, and low-molecular weight drugs [3][4][5]. These systems have been found to overcome limitations of conventional dosages forms such as improving solubility [6], bioavailability, and biodistribution of drugs [7], and targeting disease sites [8], hence contributing to a high proportion of the active drug reaching the targeted site. In addition, drug carrier systems protect the loaded drugs from premature degradation in the biological environment, thus enhancing bioavailability and cellular uptake.…”