Release Of Gentamicin Sulfate Research Articles

Lab-on-fiber optofluidic platform for in situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers.

A lab-on-fiber (LOF) optofluidic platform that provides physiologically relevant microenvironment was developed by integrating a long period grating (LPG) coupled with high order cladding mode to achieve high index sensitivity and a liquid-tight capillary tube assembly as a microfluidic chamber for LPG to mimic physiologically relevant microenvironment. We demonstrate the utility of LOF for in situ monitoring the construction of the [chitosan (CHI)/poly (acrylic acid) (PAA)/gentamicin sulfate (GS)/PAA]n multilayers at monolayer resolution as well as evaluating the rate of GS release at a flow rate of 0.127 mL/min at 37 °C in real time. We reveal that GS is released at a faster rate under the dynamic flow condition than in a static medium. Our findings underscore the importance of conducting drug release studies in physiologically relevant conditions.

Evaluation of the kinetic and relaxation time of gentamicin sulfate released from hybrid biomaterial Bioglass-chitosan scaffolds

Chitosan scaffolds, combined with bioactive glass 46S6, were prepared to serve as gentamicin sulfate delivery in situ systems for bone biomaterials. This work presents a study about the effect of the ratio chitosan/bioactive glass (CH/BG) on the release of gentamicin sulfate and on the bioactivity during in vitro experiments.SEM observations allowed understanding the bond between the glass grains and the chitosan matrix. In vitro results showed that scaffolds form a hydroxyapatite (HA) Ca10(PO4)6(OH)2 after 15 days of immersion in a simulated body fluid (SBF).The interest of this study is to see that the increase of the content of bioactive glass in the chitosan matrix slows the release of gentamicin sulfate in the liquid medium. Starting concentration of gentamicin sulfate has an influence on the relaxation time of the scaffolds. Indeed, an increasing concentration delays the return to a new equilibrium. Contents of chitosan and bioactive glass do not affect the relaxation time. Synthesized scaffolds could be adapted to a clinical situation: severity and type of infection, weight and age of the patient.

Electrochemical Impedance Spectroscopy: Evaluation of Drug Delivery System of Alpha-Tricalcium Phosphate Cement

Tricalcium phosphate cement (α-TCP) can be used in various fields of health, including as drug delivery systems. The application of a biomaterial based on α-TCP could enable both the constant drug delivery as support and shape damaged muscleskeletics tissues until which can be regenerated by the organism itself, replacing the biomaterial, while maintaining stable levels of the drug in the organism. The aim of this study was to evaluate the release of gentamicin sulfate using the technique of electrochemical impedance spectroscopy in drug delivery systems of α-TCP. The results obtained in vitro study validated the proposed methodology for assessment of controlled drug delivery systems on the basis of α-TCP.

A biomimetic extracellular matrix composed of mesoporous bioactive glass as a bone graft material

Mesoporous bioactive glass (MBG) has been demonstrated to play an important role in bone regeneration. In this study, the fabrication of a matrix composed of MBG nanofibers (MBGNFs) that mimics the three-dimensional structure of the natural extracellular matrix is reported. The fabrication process utilized a sol–gel/electrospinning technique. The morphology, composition, and structure of the MBGNF matrices were characterized. The MBGNF matrices were typically characterized by highly ordered, one-dimensional channels in a hexagonally packed mesostructure. The drug loading and release profiles of the MBGNF matrices were also investigated. MBGNF matrices had better drug-loading efficiency and could reduce the burst release of gentamicin sulfate and prolong its release over 10 days. Hence, MBGNF matrices are suitable as a drug carrier. Additionally, immersing an MBGNF matrix in a simulated body fluid resulted in the formation of a layer of bone-like apatite minerals on the surface of the MBGNFs. This finding demonstrated the excellent in vitro bioactivity of the MBGNF matrix. Based on a cellular adhesion assay and an analysis of cytoskeletal organization, we determined that MBGNF matrices provided an appropriate environment for cellular adhesion. The observed cellular proliferation; alkaline phosphatase activity; and protein expression levels of osteopontin, osteocalcin and bone sialoprotein demonstrated that MBGNF matrices promoted the proliferation, differentiation and mineralization of MG63 osteoblast-like cells. Finally, the bone regeneration ability of the MBGNF matrix was evaluated using a rat calvarial defect model. The results revealed that MBGNF matrices were biodegradable and enhanced bone regeneration. Therefore, given the above results, the MBGNF matrix has the potential to become a new bone graft material for bone tissue engineering applications.

Dynamic Release of Antibiotic Drug Gentamicin Sulfate from Novel Zirconium Phosphate Nano-Platelets

Dynamic Release of Antibiotic Drug Gentamicin Sulfate from Novel Zirconium Phosphate Nano-Platelets

In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites

Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.

Endogenously triggered electrospun fibres for tailored and controlled antibiotic release

The study was aimed at assessing the potential of enzyme-embedded antibiotic-releasing polycaprolactone (PCL)-based electrospun fibres for tunable drug delivery. This was attempted by incorporation of gentamicin sulphate (GS) in the biocompatible polymer (PCL) matrix, with the degradation of the matrix being ensured by co-impregnating a polymer-degrading enzyme (lipase). Single phase solutions were obtained by hydrophobic ion pairing of GS and surfactant coating of lipase with an anionic surfactant, docusate sodium salt Aerosol OT (AOT). By electrospinning the solution, we could produce PCL fibres containing 11% (w/w) GS–AOT and 28 U (w/w) lipase–AOT. However, sustained release of GS was not obtained. FESEM analysis showed that the fibres did not undergo the expected degradation. Subsequent experiments with unmodified lipase gave satisfactory results; the polymer underwent degradation displaying characteristic perforations in the fibres, suggestive of ‘endo-attack’. By modulating the concentrations of lipase (1 to 28 U, w/w), we could obtain GS release rates that varied from 0.53 to 32 mg/ml/d. Accordingly, the lifetime of the fibres could be tuned (10 h to 25 days). The fibres showed excellent antibacterial activity against Staphylococcus aureus throughout their lifetime.

Mechanism of Gentamicin Sulphate Release in Nanocomposite Hydrogel Drug Delivery Systems

A series of nanocomposite hydrogel drug delivery systems on the basis of polyvinyl alcohol and organically modified montmorillonite nanoclay loaded with gentamicin sulphate were prepared via the cyclic freezing-thawing method. The drug release kinetics and mechanism of the prepared drug delivery systems were determined in vitro. The results showed incorporating organically modified montmorillonite into the polyvinyl alcohol hydrogel matrix reduces the amount of released gentamicin sulphate from the system and prolongs the drug release duration. The results revealed the gentamicin sulphate release from the nanocomposite hydrogels is more prolonged with slower rate compared to the pure polyvinyl alcohol hydrogel. The results also indicated the gentamicin sulphate release mechanism for all nanocomposite hydrogel drug delivery systems is Fickian diffusion which means the gentamicin sulphate diffusion is the controlling step in the release process.

Investigation of Dynamic Release of Antibiotic Drug Gentamicin Sulphate from Cotton Cellulose/Polyacrylic Acid Composite Fibers

In this work, cotton cellulose/polyacrylic (CC/PAAc) composite fibers are produced by soaking plain cotton cellulose (CC) fibers in a reaction mixture containing monomer acrylic acid, crosslinker N,N’–methylene-bis acrylamide (MB) and initiator potassium persulphate (KPS), followed by microwave induced in-situ formation of polyacrylic acid within cotton fibers. The fibers are characterized by TGA, FTIR and SEM analysis. The mechanical strength of CC/PAAc fibers was comparable to that of CC fibers, indicating marginal loss in mechanical strength. The antibacterial drug Gentamicin Sulphate (GS) was added to the reaction mixture before soaking the CC fibers in the reaction solution. This yielded GS loaded CC/PAAc fibers. The release of drug GS was investigated as a function of the amount of crosslinker in the soaking solution. It was found that the quantity of crosslinker MB in the soaking solution influenced the release mechanism. Fiber samples with relatively lower and higher amount of crosslinker followed Second order model and the Higuchi diffusion model, respectively. The CC fibers showed lower release as compared to the CC/PAAc fibers. Finally, the biocidal action of fibers was tested using a zone of inhibition method using E. Coli as model bacteria. The fibers demonstrated biocidal action by exhibiting zones of inhibition of diameter 1.3 and 2.2 cm, respectively for fibers prepared by soaking in the reaction solutions containing 0.2 and 0.4 percent (w/v) drug. Finally, the killing kinetics was investigated to show time dependent bacterial killings for the fiber samples GSLCC/PAAc (0.2) and GSLCC/PAAc (1.2).

Coated urinary catheter by PEG/PVA/gentamicin with drug delivery capability against hospital infection

This study aimed to develop a gentamicin sulphate-releasing catheter that efficiently prevents urinary tract infections (UTIs) for short-term catheterization. The surfaces of catheters were coated with poly(ethylene glycol) (PEG) and gentamicin sulphate (GS) and subsequently poly(vinyl alcohol) (PVA). The influence of PEG molecular weight (Mw) and GS loading on the properties of the catheter were investigated, in terms of antimicrobial activity, drug release behaviour, morphology and mechanical properties. By varying the molecular weight of PEG and drug content, catheters with different surface morphologies were formed. The antimicrobial activity of samples was determined against Staphylococcus aureus and Escherichia coli. GS release profiles exhibited a biphasic release pattern that began with an initial burst release followed by a prolong release for 12 days. GS release rate increased with reduction in PEG molecular weight from 2,000 to 1,000 Da and increase in GS loading from 50 to 150 mg. Antimicrobial activity studies demonstrated that PEGs, Mw and GS loading play an important role in formation of inhibition zones: the samples with the highest molecular weight of PEG and GS loading exhibited the smallest and largest inhibition zones, respectively. The results showed that coating process led to slight increase in catheter tensile strength and Young’s modulus. Atomic force microscopy confirmed that the surface roughness was increased as a result of coating process. These findings imply that the catheters coated with PEG/PVA have a potential to control the drug release rates to a desired value for urinary catheterization.

PH-controlled delivery of gentamicin sulfate from orthopedic devices preventing nosocomial infections

Since the beginning of the 1970s, controlled release technology has witnessed great advancement, and motivated numerous researchers in materials science. These systems overcome the drawbacks of traditional drug dosage form, and offer more effective and favorable methods to optimize drug delivery in optimum dose to specific sites or to prolong delivery duration. This paper deals with the synthesis of pH-controlled drug delivery systems for bone implant, allowing the local release of gentamicin sulfate (GS), an antibiotic commonly used to prevent infections during orthopedic surgeries. We present a biomaterial synthesis allowing the controlled release of GS at the site of surgical implantation (over an adjustable period of time). In our design, spherical nanoparticles (NPs) functionalized by the chosen antibiotic (Gentamicin sulfate, GS), are chemically anchored to the biomaterial surface. A cleavage reaction of the chemical bond between NPs and GS, effected by the contact of material with a solution presenting an acidic pH (in the case of infection, there is a decrease of the physiological medium pH), induces controlled release of the bioactive molecule in its native form.In this paper, we discuss the synthesis of a bioactive titanium based biomaterial in general, and the grafting of the NPs onto the titanium surfaces in particular. We have paid particular attention to the characterization of the drug surface density and the release kinetic of the active molecule as a function of the pH. In vitro bacterial growth inhibition tests after GS delivery at acidic pH (with Staphylococcus aureus) have also been carried out in order to prove the efficiency of such biomaterials.

Injectable and bioresorbable calcium phosphate delivery systemwith gentamicin sulphate for treatment of bone diseases: in vitrostudy

In this present research, calcium phosphate cement (CPC) pastewas prepared by combining cement liquids comprised of 4 wt-% disodiumhydrogen orthophosphate with cement powders that consisted of β-tricalciumphosphate and monocalcium phosphate monohydrate. In the in vitrostudy, the release of gentamicin sulphate (GS) from standard cylindricalsamples of the prepared CPC immersion in phosphate buffered saline solutionwas measured by high performance liquid chromatography test over a periodof time. In addition, as a representative for biomedical properties, settingtime, injectability and compressive strength were measured in order to detectchanges when mixing CPC with GS. In addition, the pH values of the phosphatebuffered saline solution containing samples descended gradually until reachingequilibrium pH. Overall, the results from in vitro releasestudy showed that it reached its maximum level, which was 35% of theinitial value of the GS on day 15, suggesting no irreversible binding occurredbetween the cement paste and the antibiotic.

Synthesis of pH-Sensitive Particles for Local Delivery of an Antibiotic via Dispersion ROMP

The synthesis and the in vitro antibacterial activity of pH-sensitive functionalized nanoparticles for the local delivery of antibiotic are described. Nanoparticles (NPs) are formed by ring-opening metathesis copolymerization (ROMP) in dispersed medium of norbornene (Nb) with α,ω-functionalized macromonomers. Macromonomers are ended with gentamicin sulfate (GS) or carboxylic acid groups. GS, linked thanks to a pH-sensitive bond, can be released in acidic medium whereas acidic function allows the future covalent grafting of these NPs onto biomaterial surface in order to synthesize innovating GS-loaded biomaterials. In this paper, we focused on the synthesis and the characterization of biofunctional NPs and their in vitro antibacterial activities. NPs have been synthesized with a controlled rate of GS and their stability in aqueous medium has been proved. Minimum inhibitory concentration (MIC) measurements using Staphylococcus epidermidis as bacterial strain after the GS release at acidic pH have permitted us to prove the efficiency of this system.

Preparation and properties of calcium phosphate cements incorporated gelatin microspheres and calcium sulfate dihydrate as controlled local drug delivery system

To develop high macroporous and degradable bone cements which can be used as the substitute of bone repairing and drug carriers, cross-linked gelatin microspheres (GMs) and calcium sulfate dihydrate (CSD) powder were incorporated into calcium phosphate bone cement (CPC) to induce macropores, adjust drug release and control setting time of α-TCP-liquid mixtures after degradation of GMs and dissolution of CSD. In this study, CSD was introduced into CPC/10GMs composites to offset the prolonged setting time caused by the incorporation of GMs, and gentamicin sulphate (GS) was chosen as the model drug entrapped within the GMs. The effects of CSD amount on the cement properties, drug release ability and final macroporosity after GMs degradation were studied in comparison with CPC/GMs cements. The resulting cements presented reduced setting time and increased compressive strength as the content of CSD below 5 wt%. Sustained release of GS was obtained on at least 21 days, and release rates were found to be chiefly controlled by the GMs degradation rate. After 4 weeks of degradation study, the resulting composite cements appeared macroporous, degradable and suitable compressive strength, suggesting that they have potential as controlled local drug delivery system and for cancellous bone applications.

The Effect of Carbon Nanotubes added into Bullfrog Collagen Hydrogel on Gentamicin Sulphate Release: In Vitro

We demonstrate the preparation and its drug delivery behavior of this novel hybrid collagen-carbon nanotubes (CNTs) hydrogel obtained. CNTs can be taken as an additive to enhance the stability of the hybrid hydrogel. As a result, the sustained release effects of the hybrid hydrogel on gentamicin sulphate were significantly improved. The hybrid hydrogel combined the excellent safety of bullfrog collagen and the enhanced stability of CNTs brought to the hybrid hydrogel. It suggests that the hybrid collagen hydrogel with CNTs could be used as a novel kind of drug delivery matrix.

Gentamicin‐loaded poly(acrylic acid)‐grafted cotton fibers, part 1: Synthesis, characterization, and preliminary drug release study

AbstractThis study describes preparation of poly (acrylic acid)‐grafted cotton fibers and release of antibiotic drug gentamicin sulfate from them under physiological conditions. Poly(acrylic acid) has been grafted onto cellulose backbone of cotton fibers via Ce(IV)‐initiated polymerization in aqueous medium. The conditions obtained for optimum grafting were as follows: initiation time 30 min; initiation temperature 37°C; monomer concentration 27.8 mM; grafting temperature 30°C; nitric acid (catalyst) concentration 0.1M. The grafted fibers were characterized by FTIR, TGA, and SEM analysis. The antibiotic drug gentamicin sulfate (GS) was loaded into the grafted fibers by equilibration method and release was studied under physiological conditions. The kinetic release data was interpreted by first‐order kinetic model. Finally, drug‐loaded fibers showed fair antibacterial action against Escherichia coli. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Gentamicin sulphate release from lost foam wollastonite scaffolds using poly( dl-lactide-co-glycolide) acid

A study on the gentamicin sulphate release from lost foam wollastonite scaffolds using poly( dl-lactide-co-glycolide) acid (PLGA) was performed. Scaffolds were made through the lost foam technique using two different evaporative-patterns: poly(methyl-methacrylate) (PMMA) spheres and polyurethane (PUR) sponge. With the aim to control the rate of the gentamicin sulphate delivery, poly( dl-lactide-co-glycolide) acid was used. The porous scaffolds were gentamicin sulphate loaded by different ways. All methods showed the same gentamicin sulphate release pattern: a high rate of release in the first 24 h followed by a slow rate for a period longer than 300 h. The compression strength of the PLGA filled pores scaffolds after a degradation test was measured and compared with that of empty pores scaffolds, having as a result a notable increase in the compression strength. A hemolysis test with human blood was made to each delivery system. With only one exception, every system showed a hemolysis lower than 5%, proving to be hemocompatible. The scaffolds made by using PMMA spheres showed a better behavior in the drug release process, as well as higher mechanical properties.

Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters

The purpose of this study was to develop a suitable formulation for gentamicin sulfate (GS) that gives a sustained release of the drug. Therefore this drug was loaded into poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres. The effects of various formulation parameters (ethanol, surfactant, osmotic value of the external phase, polymer type and concentration) on particle characteristics (size, loading and release) were investigated. The GS loaded microspheres were prepared using a double emulsion evaporation technique. The results demonstrate that neither ethanol nor surfactants had beneficial effects on the drug loading efficiency (around 4-10%). However, an increase in buffer concentration (and thus osmotic pressure) of the external phase resulted in a substantial increase of GS-loading (from 10 to 28%). Further, an increase of concentration of PLGA in DCM from 10% to 15/20% caused a 4-time increase of the drug loading. The best formulation identified in this study had a loading efficiency of around 70% resulting in PLGA microspheres with a 6% (w/w) loading. The particles showed a burst release of the drug depending on their porosity, followed by a phase of 35 days where hardly any release occurred. The drug was then slowly released for around 25 days likely due to degradation of the microspheres. The drug loading efficiency of GS in PLHMGA was not significantly different from PLGA microspheres (64%). The release of GS from PLHMGA microspheres was faster than that of PLGA because the degradation rate of PLHMGA is more rapid than PLGA. This study shows that prolonged release of gentamicin can be obtained by loading this drug into microspheres made of biodegradable aliphatic polyesters.

Novel Biocatalytic Polymer-Based Antimicrobial Coatings as Potential Ureteral Biomaterial: Preparation and In Vitro Performance Evaluation

Catheters and other indwelling devices placed inside human body are prone to bacterial infection, causing serious risk to patients. Infections associated with implants are difficult to resolve, and hence the prevention of bacterial colonization of such surfaces is quite appropriate. In this context, the development of novel antimicrobial biomaterials is currently gaining momentum. We describe here the preparation and antibacterial properties of an enzyme-embedded polycaprolactone (PCL)-based coating, coimpregnated with the antibiotic gentamicin sulfate (GS). The enzyme uses PCL itself as substrate; as a result, the antibiotic gets released at a rate controlled by the degradation of the PCL base. In vitro drug release studies demonstrated sustained release of GS from the PCL film throughout its lifetime. By modulating the enzyme concentration in the PCL film, we were able to vary the lifetime of the coating from 33 h to 16 days. In the end, the polymer is completely degraded, delivering the entire load of the antibiotic. The polymer exhibited antibacterial properties against three test isolates: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Foley urinary catheters coated with the modified polymer exhibited sustained in vitro release of GS over a 60-h period. The results suggest that the antibiotic-plus-enzyme-loaded polymer can be used as tunable self-degrading antimicrobial biomaterial coating on catheters.

Diffusion loading and drug delivery characteristics of alginate gel microparticles produced by a novel impinging aerosols method

Microencapsulation of a hydrophilic active (gentamicin sulphate (GS)) and a hydrophobic non-steroidal anti-inflammatory drug (ibuprofen) in alginate gel microparticles was accomplished by molecular diffusion of the drug species into microparticles produced by impinging aerosols of alginate solution and CaCl2 cross-linking solution. A mean particle size in the range of 30–50 µm was measured using laser light scattering and high drug loadings of around 35 and 29% weight/dry microparticle weight were obtained for GS and ibuprofen respectively. GS release was similar in simulated intestinal fluid (phosphate buffer saline (PBS), pH 7.4, 37°C) and simulated gastric fluid (SGF) (HCl, pH 1.2, 37°C) but was accelerated in PBS following incubation of microparticles in HCl. Ibuprofen release was restricted in SGF but occurred freely on transfer of microparticles into PBS with almost 100% efficiency. GS released in PBS over 7 h, following incubation of microparticles in HCl for 2 h was found to retain at least 80% activity against Staphylococcus epidermidis while Ibuprofen retained around 50% activity against Candida albicans. The impinging aerosols technique shows potential for producing alginate gel microparticles of utility for protection and controlled delivery of a range of therapeutic molecules.