Preparation and Evaluation of Vancomycin-Loaded N-trimethyl Chitosan Nanoparticles

Abstract

Chronic intracellular infections caused by drug-resistant pathogens pose a challenge to the treatment of chronic osteomyelitis. Such treatment requires an intracellular delivery system for the sustained release of antibiotics such as vancomycin (VCM), which is an antibiotic of last resort used against many clinically resistant bacteria. In this work, we report VCM-loaded N-trimethyl chitosan (TMC) nanoparticles and their potential application for drug delivery. The results showed that the prepared nanoparticles were predominantly spherical in shape with an average particle diameter of 220 nm, a positive zeta potential, and a loading efficiency of 73.65%˘1.83%. Furthermore, their drug release profile followed the Higuchi model for sustained release, with non-Fickian diffusion. Over a 24-h period, 6.51%˘0.58% of the drug within the optimized nanoparticles was released. In vitro cytology showed that osteoblasts (OBs) exhibited higher alkaline phosphatase activity (ALP) after exposure to TMC nanoparticle material. Furthermore, TMC nanoparticles increased the uptake of water-soluble quantum dots (QDs) by OBs, and both nanoparticles and VCM/TMC mixtures improved OB proliferative activity. We also investigated the minimum inhibitory concentration (MIC, 60 µg/mL), half maximal inhibitory concentration (IC50, 48.47 µg/mL), diameter of inhibition zone (DIZ, 1.050 cm), Polymers 2015, 7 1851 and turbidimetric (TB) assay of nanoparticles. All data demonstrated that VCM/TMC nanoparticles had excellent antibacterial activity against the Gram-positive bacterium Staphylococcus aureus. These findings suggest that VCM-loaded TMC nanoparticles have good potential for the sustained delivery of antibiotics to bone infections.

Efficient induction of antimicrobial activity with vancomycin nanoparticle-loaded poly(trimethylene carbonate) localized drug delivery system

“…In our previous study, 17 the geometric mean diameter of VCM/TMC NPs obtained from atomic force microscopy was 200-325 nm, mean size distribution was 220-230 nm with a fairly monodisperse polydispersity index, which was almost ,0.2; meanwhile, VCM/TMC NPs carried a positive zeta potential of 14.6±0.8 mV at physiological pH, suggesting that these NPs are probably ionically stabilized against particle agglomeration due to the positive charges on their surface. In this study, the SEM results illustrated the presence of spherical VCM/TMC NPs with a smooth surface and compact structure.…”

“…17 VCM/TMC NP-PTMC was prepared according to the reported literature with a slight improvement. 22 In short, PTMC solution was prepared in a glass dish sealed by a cover by dissolving approximately 0.67 g of polymer in 25 mL THF while stirring at room temperature until complete dissolution.…”

“…15 In our study, CS was derivatized by N-methylation to N,N,N-trimethyl chitosan (TMC), a water-soluble compound, to form nanocomplexes with anionic compounds, such as drugs, proteins and DNA, through ionotropic gelation as opposed to a pH-dependent charge. 16 VCM-loaded TMC NPs (VCM/TMC NPs), prepared in our previous study, 17 proved to be an effective intracellular mode of drug administration. Additionally, the VCM/TMC NPs had an excellent probability of VCM release in the chronic osteomyelitis rabbit model.…”

On the plasma deposition of vancomycin‐containing nano‐capsules for drug‐delivery applications

“…Vancomycin is a glycopeptide antibiotic produced by Streptococcus Orientalis , well known for drug delivery applications, with a broad‐spectrum activity, including against methicillin‐resistant strains of Staphylococcus aureus . Vancomycin has often been encapsulated in spherical micro/nanoparticles made of polymeric materials such as poly(ϵ‐caprolactone), for bone implants, spray dried chitosan, or N‐trimethyl chitosan, prepared by single ionic complexation . Vancomycin‐containing coatings produced by electrodeposition and adsorption methods are also reported.…”

Novel application of trimethyl chitosan as an adjuvant in vaccine delivery

“…89 Similar sized vancomycin-loaded particles have been reported to demonstrate an efficient uptake by osteoblasts, resulting in their differentiation and elimination of the Staphylococcus aureus infection by controlled drug release. 90 It has also been suggested that the smaller NPs are easily engulfed by the APCs in comparison with the large sized ones and could potentially be used as drug delivery agent against tumors. 91 TMC NPs in the range 200-300 nm have also been reported to have more uptake as they are able to cross the nasal epithelial membrane owing to its small size.…”