Release Of Vancomycin Hydrochloride Research Articles

Facile fabrication of hollow mesoporous bioactive glass spheres: From structural behaviour to in vitro biology evaluation

Bone defects accompanied by infection or inflammation can significantly delay the healing process. To simultaneously achieve controlled release of local antibiotics for infection control and bone healing, bone-implantable delivery systems have been considered as a promising strategy. This study aims to improve drug loading capacity of bone-implantable delivery systems by introducing hollow structure mesoporous bioactive glass nanospheres (HMBGs) through a sol–gel process. Particularly, such core–shell bimodal-porous structured nanoparticles were prepared through a sacrificing template using cetyltrimethylammonium bromide (CTAB) as surfactant. It was found that varying the amount of CTAB during the synthesis process is a simple and effective approach for tuning the particle size, morphology, and structure of HMBGs. For in vitro drug release, HMBGs could sustain storage and release of vancomycin hydrochloride (VAN) via diffusion-controlled mechanism, thereby inhibiting the bacteria growth in the subsequent bacterial study. Moreover, HMBGs incorporated with VAN provided a biomimetic microenvironment favored by cell adhesion and proliferation. These findings support the compatibility of HMBG nanoparticles with antibiotics and their potential application in the treatment of infectious bone defects.

A transferosome-loaded bigel for enhanced transdermal delivery and antibacterial activity of vancomycin hydrochloride

Transdermal drug delivery is an attractive route of administration relative to other routes as it offers enhanced therapeutic efficacy. However, due to poor skin permeability of certain drugs, their application in transdermal delivery is limited. The ultra-deformable nature of transferosomes makes them suitable vehicles for transdermal delivery of drugs that have high molecular weights and hydrophilicity. However, their low viscosity, which leads to low contact time on the surface of the skin, has restricted their application in transdermal delivery. Therefore, this study aimed to deliver transferosomes loaded with a highly water-soluble and high molecular weight vancomycin hydrochloride (VCM-HCl) via a bigel for systemic delivery and treatment of microbial infections. VCM-HCl-loaded transferosomal formulations (TNFs) were prepared using a reverse-phase evaporation method and then loaded into a bigel. Both the TNFs and TNFs-loaded bigel (TNF-L-B) were characterized by a range of in vitro and ex vivo techniques. TNFs and TNF-L-B were tested for biosafety via the MTT assay and found to be biosafe. Prepared TNFs had sizes, zeta potential and entrapment efficiency of 63.02 ± 5.34 nm, −20.93 ± 6.13 mV and 84.48 ± 1.22% respectively. VCM-HCl release from TNF-L-B showed a prolonged release profile with 39.76 ± 1.6% after 24hrs when compared to bare VCM-HCl loaded in the bigel (74.81 ± 8.84%). Ex-vivo permeation of prepared TNF-L-B showed a higher permeation flux of 0.56 µg/cm2/h compared to the bare VCM-HCl-loaded bigel of 0.23 µg/cm2/h, indicating superior permeation and bioavailability of the drug. Additionally, the prepared TNF-L-B demonstrated improved antimicrobial activity. The TNF-L-B showed minimum inhibitory concentrations (MIC) of 0.97 μg/ml against Staphylococcus aureus (SA) and 1.95 μg/ml against methicillin-resistant SA (MRSA), which were 2-fold lower MIC values than the bare drug. The time-kill assay showed that both TNFs and TNF-L-B systems caused a 5.6-log reduction (100%) in MRSA compared to bare VCM-HCl after 24 hrs of incubation. Furthermore, as opposed to the bare VCM-HCl solution, the degree of biofilm reduction caused by TNFs (55.72%) and TNF-L-B (34.58%) suggests their dominance in eradicating MRSA biofilm. These findings indicate that TNF-L-B is a promising system for transdermal delivery of hydrophilic and high molecular weight drugs.

Natural resin-based solvent exchange induced in-situ forming gel for vancomycin HCl delivery to periodontal pocket

Natural resins such as benzoin, propolis and rosin have been widely employed in the pharmaceuticals. In this study, in situ forming gels (ISG) were prepared using natural resins as matrix forming agents to deliver vancomycin hydrochloride (VH) for periodontitis treatment. The formulations were investigated for their physicochemical properties, drug release and antimicrobial activities. Transformation from a solution to a solid matrix was achieved after the formulas were exposed to a simulated crevicular fluid. The rate of resin matrix formation was found to decrease with time and became more opaque owing to gradual phase separation with resin network formation. They flowed with pseudo-plastic behavior and provided appropriate injectability as well as good mechanical properties. Sustained VH release was attained for a 5-day period. VH-loaded natural resin ISGs inhibited against Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, andStreptococcus mutans.Natural resin-based ISGs comprising of propolis or benzoin showed a more effective delivery of VH than that of rosin. Thus, VH-loaded benzoin and propolis ISGs were found to have a possible application for infected periodontitis treatment.

One-pot synthesis of novel tri-component composite microspheres of polyvinyl alcohol-silica-hydroxyapatite for biomedical applications

Abstract Novel tri-component composite microspheres of polyvinyl alcohol-silica-hydroxyapatite (PVA/SiO2/HA) were prepared in a water-in-oil emulsion. The SEM results showed that the as-prepared composite microspheres with an average diameter of 23.1 μm exhibited a regular spherical shape and a high dispersity. Their inorganic phases were identified as low-crystallized hydroxyapatite and amorphous SiO2. Moreover, the PVA/SiO2/HA composite microspheres presented an enhanced capacity for both loading and sustained release of vancomycin hydrochloride (VH) as compared to their bi-component equivalents (PVA/SiO2 and PVA/HA composite microspheres), suggesting their good potential to be used as a drug carrier in bone tissue engineering.

Synthesis, Characterization, and In Vitro Drug Delivery of Chitosan-Silica Hybrid Microspheres for Bone Tissue Engineering

Chitosan-silica (CS-SiO2) hybrid microspheres were prepared through the combined process of sol-gel and emulsification-crosslinking. Their composition, morphology, in vitro bioactivity, and drug release behavior were investigated. The results showed that, when 20 wt% SiO2 was incorporated, the as-prepared CS-SiO2 hybrid microspheres exhibited a regular spherical shape, a high dispersity, and a uniform microstructure. Their average particle diameter was determined to be about 24.0 μm. The in situ deposited inorganic phase of the hybrid microspheres was identified as amorphous SiO2, and its actual content was determined by the TG analysis. As compared with the pure chitosan microspheres, the CS-SiO2 hybrid microspheres displayed a greatly improved in vitro bioactivity. Vancomycin hydrochloride (VH) was selected as a model drug. It was demonstrated that the CS-SiO2 hybrid microspheres presented a good capacity for both loading and sustained release of VH. Moreover, the increase of the SiO2 content efficiently slowed down the drug release rate of the CS-SiO2 hybrid microspheres.

Elution profiles of tobramycin and vancomycin from high-purity calcium sulphate beads incubated in a range of simulated body fluids.

The aim of this study was to characterise the elution profiles of antibiotics in combination with pharmaceutical grade calcium sulphate beads in phosphate buffered saline and other physiological solutions which more closely mimic the invivo environment. Synthetic recrystallised calcium sulphate was combined with vancomycin hydrochloride powder and tobramycin sulphate solution and the paste was formed into 3 mm diameter hemispherical beads. Then 2 g of beads were immersed in 2 ml of either phosphate buffered saline, Dulbecco's Modified Eagle Medium or Hartmann's solution and incubated at 37℃ for up to 21 days. At a range of time points, eluent was removed for analysis by liquid chromatography-mass spectrometry (LC-MS). Tobramycin sulphate and vancomycin hydrochloride release was successfully quantified against standard curves from solutions eluted in all three physiological media (phosphate buffered saline, Dulbecco's Modified Eagle Medium and Hartmann's solution) during incubation with calcium sulphate beads. One hour eluate concentrations were high, up to 2602 µg/ml for tobramycin in phosphate buffered saline and 7417 µg/ml for vancomycin, whereas in DMEM, the levels of tobramycin were 2458 µg/ml and 4401 µg/ml for vancomycin. The levels in HRT were 2354 µg/ml for tobramycin and 5948 µg/ml for vancomycin. The results show highest levels of antibiotic elution over the first 24 h, which gradually diminish over the following 21 days.

Sustained release of VH and rhBMP-2 from nanoporous magnesium-zinc-silicon xerogels for osteomyelitis treatment and bone repair.

Nanoporous magnesium–zinc–silicon (n-MZS) xerogels with a pore size ∼4 nm, a surface area of 718 cm2/g, and a pore volume of 1.24 cm3/g were synthesized by a sol–gel method. The n-MZS xerogels had high capacity to load vancomycin hydrochloride (VH) and human bone morphogenetic protein-2 (rhBMP-2), after soaking in phosphate buffered saline (PBS) for 24 hours (1.5 and 0.8 mg/g, respectively). Moreover, the n-MZS xerogels exhibited the sustained release of VH and rhBMP-2 as compared with magnesium–zinc–silicon (MZS) xerogels without nanopores (showing a burst release). The VH/rhBMP-2/n-MZS system not only exhibited a good antibacterial property but also promoted the MG63 cell proliferation and differentiation demonstrating good bactericidal activity and cytocompatibility. The results suggested that n-MZS with larger surface area and high pore volume might be a promising carrier for loading and sustained release of VH and rhBMP-2. Hence, the VH/rhBMP-2/n-MZS system might be one of the promising biomaterials for osteomyelitis treatment and bone repair.

Evaluation of the antibacterial effects of vancomycin hydrochloride released from agar–gelatin–bioactive glass composites

The aim of this work was to evaluate the perfomance of agar–gelatin (AG) composites and AG-containing 45S5 bioactive glass (BG) microparticles (AGBG) in relation to their water uptake capacity, sustained release of a drug over time, and antibacterial effects. The composites were fabricated by the gel-casting method. To impart the local drug release capacity, vancomycin hydrochloride (VC) was loaded in the composites in concentrations of 0.5 and 1 mg ml−1. VC release was assessed in distilled water at 37 °C up to 72 h and quantified spectrophotometrically. The antibacterial activity of composites was evaluated by the inhibition zone test and the plate count method. The experiments were performed in vitro up to 48 h on three staphylococcus strains: Staphylococcus aureus ATCC29213, S. aureus ATCC6538 and Staphylococcus epidermidis ATCC12228. The results showed that the addition of BG to AG composites did not affect the degree of water uptake. The release of VC was significantly affected by the presence of BG. VC release was higher from AGBGVC films than from AGVC ones over prolonged incubation times. Bacterial inhibition zones were found around the composites. The halos were larger when the cells were put in contact with AGVC composites than when they were put in contact with AGBGVC ones. Nevertheless, the viable count method demonstrated that the composites inhibited Staphylococcus cell growth with no statistical differences. In conclusion, the addition of BG did not reflect an improvement in the parameters studied. On the other hand, composites loaded with VC would have a role in prophylaxis against bacterial infection.

Incorporation of chitosan nanospheres into thin mineralized collagen coatings for improving the antibacterial effect

It is desired that the coatings on metallic implants have both excellent biological responses and good loading-release capacities of biological factors or drugs. So far, the challenge still remains, because the morphology and composition of the bioactive coatings are usually not favorable for accommodating drug molecules. In this study, we adopted an approach of incorporating chitosan nanospheres into a thin mineralized collagen coating; this approach is based on the good loading–release behavior of the nanospheres and the good cytocompatibility of the thin coating.The incorporation of chitosan nanospheres into the mineralized collagen coatings was realized by electrolytic co-deposition. The morphologies and microstructures of the resulting coatings were characterized by SEM, and the phase and chemical compositions of the coatings were measured by XRD and FTIR. The loading–release capacity for vancomycin hydrochloride (VH) was determined by ultraviolet spectrophotometry. MTS assay was used to evaluate cytocompatibility, and in vitro bacterial adhesion was tested for assessing the antibacterial effects of the VH-loaded coatings.The chitosan nanospheres adhered tightly to collagen fibrils. The incorporated coatings facilitated the sustained release of VH, and had a clear antibacterial effect.The incorporation of chitosan nanospheres into mineralized collagen coatings demonstrates an effective way to improve the drug loading–release capacity for the thin coatings. This formulation had a highly effective biological response.

Vancomycin release from poly( d, l-lactic acid) spray-coated hydroxyapatite fibers

The influence of the poly( d, l-lactic acid) (PDLLA) coating thickness on the in vitro vancomycin release from a hydroxyapatite (HA) carrier was studied. Microporous HA fibers with a porosity of 51 v% and an average pore diameter of 1.0 μm were fabricated by a diffusion-induced phase separation technique. They were loaded with 38 mg vancomycin hydrochloride (VH)/g HA, and their cylindrical shape enabled the application of the spray coating technique for the deposition of uniform PDLLA coating thicknesses, varying from 6.5 μm to 28 μm. The resulting in vitro VH release varied from a complete release within 14 days for 6.5 μm coatings to a release of 23% after 28 days for 28 μm coatings. It was clear that the VH release rate from a HA fiber can be adjusted by varying the PDLLA coating thickness. Microbiological tests of these fibers against a methicillin-resistant Staphylococcus aureus (MRSA) isolate pointed to the importance of the initial burst release and confirmed that the released antibiotics had the potential to interfere with S. aureus biofilm formation.

Towards prediction of release profiles of antibiotics from coated poly( dl-lactide) cylinders

Vancomycin hydrochloride release from coated poly( dl-lactide) cylinders was examined. The release profiles of vancomycin hydrochloride, gentamicin sulfate, and cefazolin sodium, were fitted by Fick's diffusion equation for a simple slab. Although the equation over-predicted the early release rates from cylinders with low drug loading, it served as a reasonably satisfactory tool to describe the release profiles. The effective diffusion coefficient, D eff, was critically dependent on the drug loading, drug particle size, and device length. By estimating D eff based on values obtained from vancomycin, gentamicin, and cefazolin, the release profile, from the coated cylinder, for a highly water soluble antibiotic with known particle size, can be predicted and used for device design calculations.