Evaluation of Drug-Loaded and Surface-Adsorbed DNase/Tween-80 Solid Lipid Nanoparticles against Staphylococcus aureus Biofilms.

The aim of this study was to explore the suitability of Tween-80 or DNase I adsorbed onto the surface of gentamicin-loaded solid lipid nanoparticles (SLNs) to disrupt Staphylococcus aureus biofilms in vitro. We hypothesized that surface-adsorbed DNase I or Tween-80 of SLNs will degrade the biofilm component, extracellular DNA (e-DNA), and extracellular matrix (ECM) of S. aureus biofilms. The SLNs loaded with drug (core) and surface-adsorbed disruptors (Tween-80 or DNase I) to deliver biofilm disruptors first at the site of action, which will help to break down the biofilm, and further drug release from the core will easily penetrate the biofilm and facilitate the killing of bacteria residing in S. aureus biofilms. The SLNs were synthesized by the double emulsion method; the size was 287.3 ± 7.4 nm for blank SLNs and 292.4 ± 2.36 nm for drug-loaded SLNs. The ζ-potential of blank SLNs was -25.6 ± 0.26 mV and that of drug-loaded SLNs was -13.16 ± 0.51 mV, respectively. The successful adsorption of DNase I or Tween-80 was confirmed by the activity of DNase I in blank surface-adsorbed SLNs and the change in the ζ-potential of SLNs after adsorbing DNase I or Tween-80. The surface morphology and size of the SLNs were further characterized using scanning electron microscopy. The encapsulation efficiency of the drug was 16.85 ± 0.84%. The compatibility of the drug with the excipient was confirmed by Fourier transform infrared spectroscopy and the degree of crystallinity was confirmed by X-ray diffraction (XRD) analysis. SLNs showed a sustained release of the drug up to 360 h. SLNs were easily taken up by A549 cells with minimal or no toxicity. The present study showed that Tween-80- or DNase I-adsorbed SLNs efficiently disrupt S. aureus biofilms and possess no or minimal toxicity against cells and red blood cells (RBCs).

Staphylococcus aureus Biofilm Destabilization by Tween-80 and Lung Surfactants to Overcome Biofilm-Imposed Drug Resistance.

This study is aimed to evaluating the potential of tween-80 and artificial lung surfactant (ALS) to destabilize S. aureus biofilm. The biofilm destabilization was studied by crystal violet staining, bright field microscopy, and scanning electron microscopy (SEM). During the study, S. aureus biofilm was exposed with tween-80 along various concentrations (1%, 0.1%, and 0.05%) or LS (lung surfactant) at (2.5%, 5%, and 15%) for 2 hrs. It was observed that 0.1% of tween-80 destabilized 63.83 ± 4.35% and 15% ALS 77 ± 1.7% biofilm in comparison to without treatment. The combination of tween-80 and ALS was used and showed a synergistic effect to destabilize 83.4 ± 1.46% biofilm. These results showed the potential of tween-80 and ALS as biofilm disruptors, which further needs to explore in an in-vivo animal model to access the actual potential of biofilm disruption in natural conditions. This study could play a pivotal role to overcome the problem of antibiotic resistance imposed due to biofilm formation to combat antibiotic resistance imposed by bacteria.

Synthesis and Evaluation of BSA-Loaded PLGA-Chitosan Composite Nanoparticles for the Protein-Based Drug Delivery System.

The purpose of this study was to synthesize composite nanoparticles (NPs) based on poly(d,l-lactic-co-glycolic acid) (PLGA) and chitosan (CS) and evaluate their suitability for the delivery of protein-based therapeutic molecules. Composite NPs possess a unique property which is not exhibited by any other polymer. Unlike other polymers, only the composite NPs lead to improved transfection efficiency and sustained release of protein. The composite NP were prepared by grafting CS on the surface of PLGA NPs through EDC-NHS coupling reaction. The size of bovine serum albumin (BSA)-loaded PLGA NPs and BSA-loaded PLGA-CS composite NPs was 288 ± 3 and 363 ± 4 nm, respectively. The zeta potential of PLGA NPs is -18 ± 0.23, and that of composite particles is 19 ± 0.40, thus confirming the successful addition of CS on the surface of PLGA NPs. Composite NPs were characterized using dynamic light scattering, scanning/transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, release profile, and gel electrophoresis. The encapsulation efficiency of PLGA NPs was 88%. These composite NPs were easily uptaken by the A549 cell line with no or minimal cytotoxicity. The present study emphasizes that the composite NPs are suitable for delivery of BSA into the cells with no cytotoxicity or very little cytotoxicity, while maintaining the integrity of the encapsulated BSA.