Search

The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.

Over the last few years, among controlled-release delivery systems, multivesicular liposomes (MVLs) have attracted attention due to their unique benefits as a loco-regional drug delivery system. Considering the clinical limitations of the current treatment strategies for osteomyelitis, MVLs can be a suitable carrier for the local delivery of effective antibiotics. This study aimed to prepare vancomycin hydrochloride (VAN HL) loaded MVLs using the active loading method which to the best of our knowledge has not been previously reported. Empty MVLS were prepared by the double emulsion (w/o/w) method and VAN HL was loaded into the prepared liposomes by the ammonium gradient method. After full characterization, the release profile of VAN HL from MVLs was assessed at two different pH values (5.5 and 7.4), and compared with the release profile of the free drug and also passively loaded MVLs. In vitro antimicrobial activities were evaluated using the disc diffusion method. Our results demonstrated that the encapsulation efficiency was higher than 90% in the optimum actively loaded MVL. The free VAN HL was released within 6-8 h, while the passively loaded MVLs and the optimum actively loaded MVL formulation released the drug in 6 days and up to 19 days, respectively. The released drug showed effective antibacterial activity against osteomyelitis-causing pathogens. In conclusion, the prepared formulation offered the advantages of sustained-release properties, appropriate particle size as well as being composed of biocompatible materials, and thus could be a promising candidate for the loco-regional delivery of VAN HL and the management of osteomyelitis. [ABSTRACT FROM AUTHOR]

The present study describes the use of Fe3O4 nanoparticles functionalized with cationic surfactants as sorbent for solid phase extraction of trace amounts of oxymetazoline (OXM) and vancomycin hydrochloride (VAN) from environmental water and urine samples. Cetyltrimethylammonium bromide-coated and benzalkonium chloride-coated Fe3O4 nanoparticles were used as sorbents for adsorption and desorption of orange-yellow azo dyes that formed from the coupling reaction of the studied drugs with the diazotized sulfadimidine sodium in alkaline medium. The extracted azo dyes were estimated spectrophotometrically at λmax of 496 and 442 nm for OXM and VAN, respectively. The extraction efficiency was enhanced by optimizing different parameters, such as the amount of surfactants, reagent and the sorbent, pH of the solution, sample volume, extraction time and desorption variables. Under optimum conditions, the linearity and detection limits for OXM (0.05–6, 0.028 µg/mL) and VAN (0.1–6, 0.069 µg/mL) were determined. The accuracy of the suggested method was assessed by recovery measurements on spiked environmental water samples and urine samples. High recovery percentage (96–99%) with low value of relative standard deviations (RSDs, n = 5) of less than 3.9% were achieved for both drugs.

To explore the performance of the cationic nanocarrier leciplex (LPX) in escalating the oral bioavailability of vancomycin hydrochloride (VAN) by promoting its intestinal permeability. With the aid of a D-optimal design, the effect of numerous factors, including lipid molar ratio, cationic surfactant molar ratio, cationic surfactant type, and lipid type, on LPX characteristics, including entrapment efficacy (EE%), particle size (P.S.), polydispersity index (P.I.), zeta potential value (Z.P.), and steady-state flux (Jss) were assessed. The optimized formula was further evaluated in terms of morphology, ex vivo permeation, stability, cytotoxicity, and in vivo pharmacokinetic study. The optimized formula was spherical-shaped with an E.E. of 85.2 ± 0.95%, a P.S. of 52.74 ± 0.91 nm, a P.I. of 0.21 ± 0.02, a Z.P. of + 60.8 ± 1.75 mV, and a Jss of 175.03 ± 1.68 µg/cm2/h. Furthermore, the formula increased the intestinal permeability of VAN by 2.3-fold compared to the drug solution. Additionally, the formula was stable, revealed good mucoadhesive properties, and was well tolerated for oral administration. The in vivo pharmacokinetic study demonstrated that the VAN Cmax increased by 2.99-folds and AUC0-12 by 3.41-folds compared to the drug solution. These outcomes proved the potentiality of LPX in increasing the oral bioavailability of poorly absorbed drugs. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The preferred test methods for control of product-related impurities in medicinal products are high-performance liquid chromatography (HPLC) with a fine sorbent, and ultra-performance liquid chromatography (UPLC), which allow for better chromatographic separation of active substances and related impurities, reduction of time costs, and saving of material resources. The aim of the study was to develop HPLC and UPLC test procedures and assess the chromatographic separation capacity and efficiency in order to improve determination of the main vancomycin component and related impurities. Materials and methods: vancomycin hydrochloride lyophilisate for oral solution and solution for injection, and vancomycin hydrochloride reference standard (USP RS) were used as test objects. Agilent 1290 Infinity liquid chromatography system, and Chromolith® Performance RP-18e, Kinetex C18, Nucleodur C18 Isis, Zorbax RRHD Eclipse Plus C18, and LiChrospher® RP-18 columns were used for the testing. Results: HPLC analysis using a Chromolith® column (100×4.6 mm) reduces the testing time by 10 minutes compared to the USP test procedure, and by 15 minutes compared to the British Pharmacopoeia procedure. The proposed test procedure requires less eluent and increases chromatographic separation efficiency. UPLC analysis using a Kinetex C18 column (50×4.6 mm, 2.6 μm) made it possible to reduce the testing time by two thirds compared to the British Pharmacopoeia procedure. The use of isocratic elution greatly simplified the testing. The testing time under the proposed chromatographic conditions was 10 minutes. Conclusions: the selected HPLC and UPLC test conditions made it possible to significantly reduce the time of testing, minimise the use of expensive reagents, and increase efficiency of chromatographic separation in the determination of vancomycin impurities and the main component Vancomycin B.

The purpose of this study was to develop a thermosensitive in situ gel delivery system based on Poloxamer 407 and Poloxamer 188 for ocular administration of vancomycin to treat systemic diseases. The vancomycin thermosensitive in situ gel was characterized using differential scanning calorimetry, rheological and drug release analyses. Additionally, pharmacokinetic studies and irritation tests of the gel were conducted after ocular administration in rabbits. The gel maintained a flowing liquid state under non-physiological conditions (25°C) to facilitate administration, and it transformed into a semi-solid state under physiological conditions (dilution with tears, 34°C), which prolonged its retention time in the eye. The gel erosion and drug release tests showed an excellent linear relationship between the cumulative drug release rate and the cumulative gel erosion rate, indicating a zero-order kinetic process. The pharmacokinetic analyses showed that the peak concentration, area under the curve, and bioavailability of the vancomycin thermosensitive in situ gel were 1.44, 1.98 and 1.93 times greater, respectively, that the values of vancomycin eye drops. Therefore, thermosensitive in situ gel may serve as a drug delivery system that can overcome the limitations of existing formulations of small-molecule peptides. [Display omitted] [ABSTRACT FROM AUTHOR]

Vancomycin hydrochloride (VANH) is a glycopeptide antibiotic commonly employed in the prophylaxis and therapy of various gram-positive bacterial life-threatening infections. Due to the narrow therapeutic window of VANH, its serum levels should be well-monitored to avoid its toxicity and to optimize its therapy. Herein, an innovative silver-nanoparticles enhanced fluorescence technique was designed for VANH rapid analysis in its pharmaceutical formulation and biological fluids. This technique is based on reinforcement of VANH fluorescence intensity with silver-nanoparticles that were synthesized by a redox reaction between VANH and silver nitrate in NaOH alkaline medium using polyvinylpyrrolidone as a stabilizer. The produced silver-nanoparticles were characterized by using UV–visible spectroscopy where they have an intense absorption maximum at 415 nm and transmission electron microscope (TEM) micrograph where they are spherical in shape with smooth surface morphology and size of 10.74 ± 2.44 nm. The fluorescence intensity was measured at 394 nm after excitation at 259 nm. Under optimum conditions, a good linear relationship was accomplished between the VANH concentration and the fluorescence intensity in a range of (1–36) ng/mL with a limit of detection of 0.29 ng/mL. Greenness assessment was performed using two assessment tools namely; eco-scale scoring and green analytical procedure index revealing excellent greenness of the proposed technique. The proposed technique was validated according to the International Conference on Harmonisation (ICH) recommendations and statistically compared with the reported HPLC method revealing no significant difference concerning accuracy and precision at p = 0.05. The proposed technique depended primarily on water as a cheap and eco-friendly solvent. [ABSTRACT FROM AUTHOR]

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

BACKGROUND: Oxidized hydroxypropyl methylcellulose-sodium hyaluronate hydrogel system exerts perfect mechanical properties, biocompatibility, and degradability, can be employed as a tissue engineered scaffold to protect and support injured tissues, and can also be applied as a drug carrier to achieve a regional sustained-release effect. OBJECTIVE: To prepare sustained-release antibacterial microsphere composite tissue-engineered material hydrogel, and investigate its physical and chemical, biological, osteoinductive, and antibacterial properties. METHODS: Using poly(lactic-co-glycolicacid), chitosan, and sodium hyaluronate as materials, a porous microsphere carrier with a multilayer structure was prepared by the emulsion method. Vancomycin hydrochloride was loaded to prepare sustained-release antibacterial microspheres. Oxidized hydroxypropyl methylcellulose-hydrazide-modified sodium hyaluronate was utilized as the matrix to prepare an injectable hydrogel. Different mass concentrations of antibacterial sustained-release microspheres (0.1, 0.2, and 0.3 g/mL) were added to the hydrogel to prepare an injectable hydrogel containing sustainedrelease antibacterial microspheres. The physical and chemical properties (determination of gel-forming time, swelling performance, degradation performance), biological properties (cytotoxicity, cell hemolysis), and osteogenic properties (alkaline phosphatase activity and osteogenic genes RUN-x2, bone morphogenetic protein 2, osteocalcin, type I collagen expression levels), and antibacterial properties were tested and evaluated. RESULTS AND CONCLUSION: (1) The three kinds of sustained-release antibacterial microsphere hydrogels had good gel-forming properties and a small swelling ratio. The in vitro degradation scanning electron microscope results exhibited that the hydrogels had stable self-degradation properties. (2) The cytotoxicity experiment displayed that when the added number of sustained-release antibacterial microspheres was less than or equal to 0.2 g/mL, the hydrogel did not have remarkable cytotoxicity (the relative growth rate of cells within 7 days was all greater than 80%). The hemolysis experiment demonstrated that cell hemolysis rate of three kinds of the sustained-release antibacterial microsphere hydrogel was less than 2%, without obvious cell hemolysis. (3) Three kinds of sustained-release antibacterial microsphere hydrogels could increase the osteogenic gene RUN-x2, bone morphogenetic protein 2, type I collagen, osteocalcin contents, and alkaline phosphatase production in MG-63 cells. (4) These hydrogels could suppress the growth of Staphylococcus aureus continuously and for a long time, and the antibacterial ability of the hydrogels increased with the increased amount of sustained-release antibacterial microspheres. (5) These results show that the prepared injectable antibacterial microsphere hydrogel has perfect sustained-release antibacterial, osteogenic, and osteoinductive capabilities, as well as good biohistocompatibility and degradability. [ABSTRACT FROM AUTHOR]

Drugs can be toxic to the fetus depending on the amount that permeates across the maternal–fetal barrier. One way to limit the amount which penetrates this barrier is to increase the molecular size of the drug. In this study, we have achieved this by encapsulating our model antibiotic (vancomycin hydrochloride, a known nephrotoxic agent) in liposomes. PEGylated and non-PEGylated liposomes encapsulating vancomycin hydrochloride were prepared using two different methods: thin-film hydration followed by the freeze–thaw method and the reverse-phase evaporation method. These liposomes were characterized by their hydrodynamic size and zeta potential measurements, CryoTEM microscopy, loading and encapsulation efficiency studies, in vitro release measurements and in vitro cytotoxicity assays using NRK-52 E rat kidney cells. We also determined the in vitro permeability of these liposomes across the human placental cell and dog kidney cell barriers. Vancomycin hydrochloride-loaded PEGylated liposomes (VHCL-lipo) of a size less than 200 nm were prepared. The VHCL-lipo were found to have the faster release of vancomycin hydrochloride and resulted in greater viability of NRK-52E cells. In vitro, the VHCL-lipo permeated the human placental cell and dog kidney cell barriers to a lesser extent than the free vancomycin hydrochloride. The data suggest a reduction in nephrotoxicity and permeability of vancomycin hydrochloride after encapsulation in PEGylated liposomes. [ABSTRACT FROM AUTHOR]

Continuous flow injection (CFI)-spectrophotometric method has been developed for oxymetazoline (OXY) and vancomycin hydrochloride (VAN) determination in pure and dosage forms. Sulfadimidine drug was used as a safe chromogenic reagent by diazotization coupling with studied drugs to produce sensitive azo dyes with maximal wavelengths of 498 and 441 nm, respectively, for OXY and VAN drugs. The effect of various chemical and physical conditions on the signal response has been studied. Under optimum conditions, Beer's law was linear over the concentration range of 5-200 and 6-200 µg/mL with limits of detection of 2.19 and 1.79 µg/mL for OXY and VAN, respectively. The CFI systems gave a sample throughput of more than 120 samples per hour for 150 µL injection volume for both drugs. The proposed methods were used for the estimation of microgram quantities of both drugs in their different dosage forms with great effectiveness. The method's validity and applicability were thoroughly investigated and the recoveries values were compared with those of standard pharmacopeia methods. The specified approaches were used without the excipients interfering in pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Currently, the treatment of osteomyelitis poses a great challenge to clinical orthopedics. The use of biodegradable materials combined with antibiotics provides a completely new option for the treatment of osteomyelitis. In this study, vancomycin hydrochloride (VANCO) loaded poly (lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double emulsion solvent evaporation method, and the in vitro drug release behaviors of the drug loaded microspheres were explored after coating with different concentrations of silk fibroin (SF). Drug loading, encapsulation efficiency, Scanning electron microscopy, particle size analysis, Fourier transform infrared spectroscopy, hydrophilicity, in vitro drug release, and in vitro antibacterial activity were evaluated. The results showed that the drug loading of vancomycin loaded PLGA microspheres was (24.11 ±1.72)%, and the encapsulation efficiency was (48.21 ±3.44)%. The in vitro drug release indicated that the drug loaded microspheres showed an obvious initial burst release, and the drug loaded microspheres coated with SF could alleviate the initial burst release in varying degrees. It also can reduce the amount of cumulative drug release, and the effect of microspheres coated with 0.1% concentration of SF is the best. The time of in vitro drug release in different groups of drug loaded microspheres can be up to 28 days. The microspheres coated with (0.1%SF) or without (0%SF) SF showed a cumulative release of (82.50±3.51)% and (67.70±3.81)%,respectively. Therefore, the surface coating with SF of vancomycin loaded microspheres can alleviate the initial burst release, reduce the cumulative drug release, potentially prolong the drug action time, and improve the anti-infection effect. [ABSTRACT FROM AUTHOR]

BACKGROUND: Local antibiotic slow-release system can solve the problems of total toxicity caused by systemic antibiotics and short half-life of short-term local antibiotics. OBJECTIVE: To prepare polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres loaded with vancomycin and evaluate its performance. METHODS: Vancomycin-loaded polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres and unloaded polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite microspheres were prepared by emulsion method. Mass concentrations of vancomycin in the drug-loaded microspheres were 25, 50, and 100 g/L. The drug-loading amount, encapsulation efficiency, and in vitro sustained release properties of the drug-loaded microspheres were detected. The three kinds of drug-loaded microspheres were co-cultured with Staphylococcus aureus bacteria separately, and the antibacterial rate was detected within the corresponding time points. The four kinds of microsphere extracts were co-cultured with MC3T3-E1 cells and MG-63 cells, and the cytotoxicity was detected by CCK-8 method after 1, 3, and 7 days of culture. RESULTS AND CONCLUSION: (1) The encapsulation efficiencies of 25, 50, and 100 g/L drug-loaded microspheres were (79.70±5.11)%, (86.41±3.91)%, and (63.18±1.96)%, and the drug loading was (3.98±0.26)%, (8.64±0.39)%, and (12.63±0.39)%. The encapsulation efficiency of 50 g/L drug-loaded microspheres was higher than that of 100 g/L drug-loaded microspheres (P < 0.05). The drug loading of 100 g/L drug-loaded microspheres was higher than that of the other two groups (P < 0.05). (2) Three kinds of drug-loaded microspheres had no obvious burst release within 24 hours, of which the drug release rate of 50 g/L drug-loaded microspheres at different time points was faster than that of the other two groups. The drug release amount of 100 g/L drug-loaded microspheres at different time points was higher than that of the other two groups, and the drug mass concentration of the three groups was higher than minimum antibacterial concentration of vancomycin at 56 days. (3) All three kinds of drug-loaded microspheres could effectively kill Staphylococcus aureus within a certain period of time. From 14 to 28 days, the relative colony rate of the three kinds of microspheres was lower than 3%, indicating that three kinds of drug-loaded microspheres can continuously and effectively kill Staphylococcus aureus. (4) The 25 and 50 g/L drug-loaded microspheres have no obvious cytotoxicity to MC3T3-E1 cells and MG-63 cells, and 100 g/L drug-loaded microspheres have certain cytotoxicity. (5) The results show that the VA@PLGA-CS-HA microspheres have good sustained-release performance, antibacterial ability and biological tissue compatibility. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.

To explore the performance of the cationic nanocarrier leciplex (LPX) in escalating the oral bioavailability of vancomycin hydrochloride (VAN) by promoting its intestinal permeability. With the aid of a D-optimal design, the effect of numerous factors, including lipid molar ratio, cationic surfactant molar ratio, cationic surfactant type, and lipid type, on LPX characteristics, including entrapment efficacy (EE%), particle size (P.S.), polydispersity index (P.I.), zeta potential value (Z.P.), and steady-state flux (Jss) were assessed. The optimized formula was further evaluated in terms of morphology, ex vivo permeation, stability, cytotoxicity, and in vivo pharmacokinetic study. The optimized formula was spherical-shaped with an E.E. of 85.2 ± 0.95%, a P.S. of 52.74 ± 0.91 nm, a P.I. of 0.21 ± 0.02, a Z.P. of + 60.8 ± 1.75 mV, and a Jss of 175.03 ± 1.68 µg/cm2/h. Furthermore, the formula increased the intestinal permeability of VAN by 2.3-fold compared to the drug solution. Additionally, the formula was stable, revealed good mucoadhesive properties, and was well tolerated for oral administration. The in vivo pharmacokinetic study demonstrated that the VAN Cmax increased by 2.99-folds and AUC0-12 by 3.41-folds compared to the drug solution. These outcomes proved the potentiality of LPX in increasing the oral bioavailability of poorly absorbed drugs.

Drugs can be toxic to the fetus depending on the amount that permeates across the maternal–fetal barrier. One way to limit the amount which penetrates this barrier is to increase the molecular size of the drug. In this study, we have achieved this by encapsulating our model antibiotic (vancomycin hydrochloride, a known nephrotoxic agent) in liposomes. PEGylated and non-PEGylated liposomes encapsulating vancomycin hydrochloride were prepared using two different methods: thin-film hydration followed by the freeze–thaw method and the reverse-phase evaporation method. These liposomes were characterized by their hydrodynamic size and zeta potential measurements, CryoTEM microscopy, loading and encapsulation efficiency studies, in vitro release measurements and in vitro cytotoxicity assays using NRK-52 E rat kidney cells. We also determined the in vitro permeability of these liposomes across the human placental cell and dog kidney cell barriers. Vancomycin hydrochloride-loaded PEGylated liposomes (VHCL-lipo) of a size less than 200 nm were prepared. The VHCL-lipo were found to have the faster release of vancomycin hydrochloride and resulted in greater viability of NRK-52E cells. In vitro, the VHCL-lipo permeated the human placental cell and dog kidney cell barriers to a lesser extent than the free vancomycin hydrochloride. The data suggest a reduction in nephrotoxicity and permeability of vancomycin hydrochloride after encapsulation in PEGylated liposomes.

The objective of this study was to compare the pharmacokinetics of vancomycin hydrochloride administered into rabbits through different routes and explore the feasibility of peptide drugs entering the systemic circulation through ocular administration. A convenient, accurate, and rapid liquid chromatography-trandem mass spectrometric (LC-MS/MS) method was established and used for the determination of vancomycin hydrochloride in rabbit plasma after intravenous administration (1.5 mg/kg), intragastric, and ocular administration (15 mg/kg). The pharmacokinetic parameters were analyzed using the DAS 2.0 software. We obtained a linear calibration curves vancomycin hydrochloride in plasma of rabbits over a concentration range of 0.05–10.0 μg/mL (R2 > 0.9995), the interassay accuracy was within 5%, precision of 1.66–3.38%, and recovery of >85%. No matrix effects were observed. The absolute bioavailability of vancomycin hydrochloride after intragastric and ocular administration was 1.0 and 7.3%, with the half-life values of 63.1 and 138.5 min, respectively. Therefore, the LC-MS/MS method established in this experiment was suitable for the determination of vancomycin hydrochloride. Vancomycin hydrochloride was rapidly absorbed into the blood circulation after ocular administration. Ocular administration was linked to higher bioavailability compared with intragastric administration, suggesting that the former will become a route for the delivery of peptide drugs. [ABSTRACT FROM AUTHOR]

Magnetic solid-phase extraction is an efficient and low-cost spectrophotometric method that can be utilized for extraction and determination of pharmaceutical compounds. Vancomycin is an antibiotic used in the treatment of life-threatening infections caused by Gram-positive bacteria. This study utilized magnetic solid-phase extraction for the determination of vancomycin hydrochloride (VAN) in different matrices. The separation and determination performed on magnetic iron oxide nanoparticles (IONPs) was modified using cetyltrimethylammonium bromide (CTAB). An azo dye product results from the coupling of VAN with the diazotized 4-aminoacetophenone in alkaline medium. This product was extracted and measured spectrophotometrically at λmax of 456 nm. Factors affecting the efficiency of removing the dye, such as pH of the solution, volume of reagent, CTAB amount, adsorbent amount, extraction time and desorption conditions, were studied. Under optimal extraction conditions, the linearity concentrations range was 0.1–6 µg/mL. The limit of detection and the limit of quantification was calculated to be 0.075 and 0.25 µg/mL, respectively. The method was applied successfully for the fast analysis of VAN in its dosage forms using the CTAB-coated IONPs, and the extraction process could be completed within 10 min. [ABSTRACT FROM AUTHOR]

Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In this study, a medicated osteoinductive and bioresorbable bone graft was designed and investigated for its ability to control antibiotic drug release in situ. This represents an ideal solution for the eradication or prevention of infection, while simultaneously repairing bone defects. Vancomycin hydrochloride and gentamicin sulfate, here considered for testing, were loaded into a previously developed and largely investigated hybrid bone-mimetic scaffold made of collagen fibers biomineralized with magnesium doped-hydroxyapatite (MgHA/Coll), which in the last ten years has widely demonstrated its effective potential in bone tissue regeneration. Here, we have explored whether it can be used as a controlled local delivery system for antibiotic drugs. An easy loading method was selected in order to be reproducible, quickly, in the operating room. The maintenance of the antibacterial efficiency of the released drugs and the biosafety of medicated scaffolds were assessed with microbiological and in vitro tests, which demonstrated that the MgHA/Coll scaffolds were safe and effective as a local delivery system for an extended duration therapy—promising results for the prevention of bone defect-related infections in orthopedic surgeries.

• A scaffold of silk fibroin/oxidized pectin (SF/OP) based on Schiff mechanism has been prepared. • Fragmented (PLLA)-drug fibers were added to the hydrogel structures. • Scaffolds demonstrated sustainable release of vancomycin. Controlled release of vancomycin hydrochloride (vanco HCl) in order to enhance therapeutic effects and to reduce toxic effects of systemic administration has received a lot of interest in recent years. In the present study, a hydrogel scaffold of silk fibroin/oxidized pectin (SF/OP) based on Schiff mechanism has been prepared. To prevent bone infection or treat osteomyelitis, vanco HCl was loaded into the scaffolds. For obtaining sustained release of vanco HCl, electrospun fibers of poly (l -lactide) (PLLA)-drug were aminolyzed and then added to the hydrogel. The results of many techniques that assessed on scaffolds demonstrated that incorporation of aminolyzed fibers into the hydrogel resulted in 61% reduction of drug release content. Moreover, 15% decrease in swelling ratio, 52% increase in crosslinking density and 30% increase in compressive modulus were observed. Antibacterial effect of scaffolds against methicillin resistant Staphylococcus areous (MRSA) was proved and also nontoxicity versus human adipose derived mesenchymal stem cells (hAD-MSCs) was confirmed by MTT assay. In conclusion, the presence of aminolyzed PLLA-drug fibers in SF/OP hydrogel made this delivery system very promising in sustained release of vanco HCl. [ABSTRACT FROM AUTHOR]

Lyotropic bulk reversed hexagonal and reversed cubic liquid crystalline phases (hexagonal and cubic phases) composed of glycerol monooleate (GM) were used to design the vancomycin hydrochloride's (VHCl) delivery systems aiming to maintain VHCl's therapeutic concentration during 24 h in the eye, locally (as an insert) and/or intravitreally (as a bulk phase injection). Bulk VHCl's hexagonal and cubic phases were successfully prepared by melted homogenization and solvent evaporation method, and then an insert was prepared. The structural characteristics of liquid crystalline phases were studied using cross polarized light microscopy and small angle X-ray scattering technique. The presence of VHCl (1–9.5% w/w VHCl solution) did not exhibit any change in the liquid crystalline phase's structure to another liquid crystalline phase, and showed little effect on the lattice parameter of the existing liquid crystalline phase structure. In order to relate the liquid crystalline phase structure to VHCl's release rate locally into the eye, in - vitro release test of an implant has been done using a simulated tear fluid. VHCl's release in the simulated tear fluid from the cubic phase obeyed Higuchi kinetics, with linear VHCl's release versus the square root of time. The hexagonal phase released VHCl in simulated tear fluid significantly slower than the cubic phase. In order to relate the liquid phase structure to VHCl's diffusion intravitreally, in vitro release test by the Sirius' Subcutaneous Injection Site Simulator (Scissor) has been performed. Comparing the release properties by a Scissor , the VHCl's cubic phase demonstrated slower permeation through extra-cellular matrix than the VHCl solution. To evaluate the efficacy of the system investigated, the release properties of VHCl's cubic phase were compared with literature data indicating that the cubic phase could be a potential matrix system in the delivery of VHCl intravitreally during 24 h after intravitreal injection. The release data in the simulated tear fluid indicated that the cubic phase should be further optimized to achieve a therapeutic VHCl concentration locally in the eye during 24 h. [ABSTRACT FROM AUTHOR]

The influence of two tuning agents, polyglycerol ester (PE) and triblock copolymer (TC), on the properties of glycerol monooleate (MO) liquid crystalline phase (LCP) was investigated to achieve the therapeutic concentration of vancomycin hydrochloride (VHCl) into the eye, topically during 60 min (1 h) and intravitreally during 2880 min (48 h). Different techniques were used to elucidate the impact of surfactants on the structure of the LCP: polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and in vitro release tests I and II (simulating local and intravitreal application in the eye). The structure analysis by SAXS depicts that the inclusion of PE into the MO LCP provided partial transition of a hexagonal phase into a lamellar phase, and TC induced a partial transition of a hexagonal phase into an LCP which identification was difficult. The LCP modulated with PE and TC demonstrated different VHCl’s release patterns and were evaluated by comparing our release data with the literature data. The comparison indicated that the LCP modulated with 30% w/w PE could be a promising VHCl delivery system intravitreally during 2880 min.

The antibiotic administration is critical for treating open fracture, especially for tainted bone caused by contamination and the implant. Localized delivery of antibiotics is preferred since it provides elevated antibiotic concentrations at the aiming infection site without systemic toxicity. In this study, a polymer-based composite film with high drug loading capacity and excellent controlled release behavior that can be potentially applied as antibiotics-carrying implants is proposed. First, vancomycin hydrochloride (VH) loaded polyvinyl alcohol-borax (PVA-B) microgels were deposited on the surface of Ti metal straight bone plate by an electrospray technique, porous polyvinyl butyral (PVB) fiber felts were then covered onto the surface of the VH@PVA-B films using electrospinning technique in order to prohibit the free diffusion of VH molecules. The density and size of the pores in the fiber felts can be readily adjusted by exposing the fiber felts to the saturated ethanol vapor, which further controlling the release behavior of the VH molecules from the VH@PVA-B/PVB systems. Importantly, the results showed that our VH@PVA-B/PVB systems with different release behaviors adjustable by the density and size of the pores are all effective to kill S. aureus, as the released VH concentration from the investigated systems are all well above the minimum effective concentration. This study provides a universal strategy to fabricate therapeutic drugs-loaded coatings on implants with the ability to control drug release behaviors. [ABSTRACT FROM AUTHOR]

Antibiotic use is an essential method for the treatment of bacterial infections. In certain cases, antibiotics are not effective because of the distribution problems caused by physiological barriers in the body. Such problems are thought to be minimized by development of sustained release systems which involve implantation of antibiotic loaded polymeric systems directly to the site of infection. In this work, a new composite vancomycin hydrochloride release system based on HPMC microparticles and chitosan/glycerophosphate (Ch/Gp) thermosensitive hydrogel was designed for the aim of local treatment of osteomyelitis. Vancomycin-loaded HPMC microparticles (Van-HPMCs) were prepared by spray drying method. The SEM results showed that these particles had a mean diameter of 1.5-6.4 lm with a narrow size distribution and homogeneous particle production. Their drug encapsulation efficiency was 72.6%. The Van-HPMCs were embedded in an injectable Ch/Gp solution to introduce a composite drug release platform (Van/HPMC-Ch/Gp). In vitro release studies indicated that inclusion of the Van- HPMCs into the Ch/Gp hydrogel caused a reduction in both the release rate and total amount of vancomycin release, which suggests that HPMC microparticles entrapped into the Ch/Gp hydrogels showed more suitable sustained release kinetics for local antibiotics delivery. [ABSTRACT FROM AUTHOR]

UV-spectrophotometry refers to absorption spectroscopy or reflectance spectroscopy in the ultraviolet-visible spectral region. This method of analysis is gaining importance as it is rapid, simple, precise, less time consuming and highly accurate. The objective of the present investigation was to develop an accurate, rapid and robust method for determination of Vancomycin hydrochloride in pharmaceutical preparations by using UV spectrophotometric method. Vancomycin hydrochloride shows maximum absorbance at a wavelength of 281 nm, which is used for this study. The method provides a linear response from a quantitation range of 20 ìg/ml to 100 ìg/ml in phosphate buffer pH 6.8 with regression equation y = 0.0038x + 0.0045 and r2 0.9994. Interday precision and accuracy was found to be below 0.2 and above 99.00% respectively for the developed method. Thus the developed method may be suitably applied for regular quality control of Vancomycin hydrochloride in bulk and pharmaceutical preparations. [ABSTRACT FROM AUTHOR]

[Display omitted] Drug-loaded emulsions for spray drying should be optimised for their rheological behaviour and stability under operating conditions, as this is essential for achieving the desired physicochemical properties of the final dry product. Our aim was therefore to investigate the structure and stability of a water-in-oil (W/O) emulsion containing vancomycin hydrochloride as the active ingredient in the aqueous phase, poly(d , l -lactide- co -glycolide) as the structural polymer in the dichloromethane-based organic phase, and various stabilisers using low-field nuclear magnetic resonance (LF NMR) and rheological characterisation. Four emulsions were tested, namely-one without stabiliser, one with Poloxamer® 407, one with chitosan and Span™ 80 and one with chitosan only. The theoretical interpretation of the rheological data allowed the determination of the velocity and the shear rate/stress profiles inside the feed path of the W/O emulsion, aspects that are critical for the industrial scale-up of the emulsion drying process. In addition, LF NMR demonstrated that shaking was sufficient to restore the original emulsion structure and that the droplet size of all emulsions was in the range of 1–10 μm, although the emulsion with chitosan had the narrowest droplet size distribution and the higher zero shear viscosity, which accounts for the increased long-term stability due to impeded droplets movement. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate transdermal delivery of vancomycin hydrochloride using the combination of ethosomes as an encapsulating vesicle and iontophoresis. Ethosomes were prepared and evaluated in terms of electrochemical stability. Cathodal iontophoresis of negatively charged ethosomes and anodal iontophoresis of free drug solution and positively charged vesicles were conducted. The effect of current mode, density, concentration of drug and ionic strength was studied.In vivostudy was performed by inducing mediastinitis in Sprague-Dawley rats using methicillin-resistantStaphylococcus aureusas infected pathogen, the mean bacterial count was compared between groups of rats, one of the treated groups received drug intramuscularly while the other group received vancomycin using iontophoretic delivery of optimized ethosomal formula. Ethosomes showed efficient electrochemical stability, cathodal iontophoresis of negatively charged vesicle (F2) showed maximum transdermal flux (550 µg/cm2/h) compared to free drug solution and other ethosomal formulae, transdermal flux was reduced by altering current mode from continuous to ON/OFF mode, reducing current density and by using normal saline as drug solvent; on the other hand, flux was potentiated by increasing drug concentration from 25 to 75 mg/ml.In vivostudy revealed that there was a significant difference in terms of bacterial count between untreated and treated groups, while there was no statistically significant difference between the I.M. vancomycin treatment and treatment conducted by iontophoretic delivery of vancomycin encapsulated in ethosomal formula. Combination between ethosomes and iontophoresis had succeeded in delivering vancomycin transdermally. [ABSTRACT FROM PUBLISHER]

The present work evaluated the feasibility of chitosan coated liposomes (c-Lips) for the intravenous delivery of vancomycin hydrochloride (VANH), a water-soluble antibiotic for the treatment of gram-positive bacterial infections like osteomyelitis, arthritis, endocarditis, pneumonia, etc. The objective of this research was to develop a suitable drug delivery system in vivo which could improve therapeutic efficacy and decrease side effects especially nephrotoxicity. Firstly, the vancomycin hydrochloride liposomes (VANH-Lips) were prepared by modified reverse phase evaporation method, then the chitosan wrapped vancomycin hydrochloride liposomes (c-VANH-Lips) nanosuspension was formulated by the method of electrostatic deposition. Based on the optimized results of single-factor screening experiment, the c-VANH-Lips were found to be relatively uniform in size (220.40 ± 3.56 nm) with a narrow polydispersity index (PI) (0.21 ± 0.03) and a positive zeta potential (25.7 ± 1.12 mV). The average drug entrapment efficiency (EE) and drug loading (DL) were 32.65 ± 0.59% and 2.18 ± 0.04%, respectively. The in vitro release profile of c-VANH-Lips possessed a sustained release Characterization and the release behavior was in accordance with the Weibull equation. Hemolysis experiments showed that its intravenous injection had preliminary safety. In vivo, after intravenous injection to mice, c-VANH-Lips showed a longer retention time and higher AUC values compared with the VANH injection (VANH-Inj) and VANH-Lips. In addition, biodistribution results clearly demonstrated that c-VANH-Lips preferentially decreased the drug distribution in kidney of mice after intravenous injection. These results revealed that injectable c-VANH-Lips may serve as a promising carrier for VANH to increase therapeutic efficacy on gram-positive bacterial infections and reduce nephrotoxicity, which provides significantly clinical value for long-term use of VANH. [ABSTRACT FROM AUTHOR]