Release Of Gentamicin Sulfate Research Articles

In vitro release dynamics of doxorubicin hydrochloride & gentamicin sulphate through nanoparticle embedded sterculia gum/gelatin self crosslinked hydrogel system

Present study synthesized stimuli-sensitive drug delivery systems for anti-cancer drug doxorubicin hydrochloride (Dox) and antibiotic drug gentamicin sulphate (GS) using sterculia gum, gelatin, and Fe3O4 nanoparticles. The approach involved oxidizing sterculia gum with NaIO4, followed by self-crosslinking with gelatin resulting a pH-responsive protein hybrid crosslinked network. Further gel matrix was reinforced with Fe3O4 nanoparticles resulted in magnetic nanocomposite hydrogel. FTIR, powdered XRD, and FESEM had been used to characterize the functionalized drug-loaded hydrogels. In vitro release behavior of Dox and GS had been studied in pH 2.2, 7.0, 7.4, simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). For both drugs, highest release had been achieved in pH 2.2 and SGF, while minimum in physiological pH 7.4. The release mechanisms adopted by Dox and GS from drug loaded OSG-cl-Gelatin and OSG-cl-Gelatin/Fe3O4 matrix have been assessed using different mathematical models viz Zero order, First order, Higuchi kinetic model and Korsmeyer Peppas model in different release mediums. Drug release mainly had occurred through Case-II diffusion mechanism. In acidic pH, Dox release followed Higuchi kinetic model while GS release occurred through Korsmeyer Peppas model. Hydrolytic degradation potential, thrombogenicity and haemocompatible behavior of functionalized gel matrix had also been screened.

Extremely low friction coefficient and mechanically robust photonic film towards antibiotic drug release

Excessive friction between hydrogels and biological tissue is a major risk factor that can lead to tissue damage and inflammation, limiting their application as biomaterials. Herein, we designed a photonic hydrogel film with an extremely low friction coefficient (COF∼1.71 × 10−3) by embedding free linear polyacrylamide (PAAm) polymer chains within a thermosensitive hydrogel matrix. This photonic hydrogel with brush structure possesses elastic deformation and reversible color change due to its excellent mechanical property. As proof-of-concept, gentamicin sulfate (GS) was selected as model of antibiotic drug, the structural color of material changes during the release of GS. Consequently, the cumulative release amount of the GS can be evaluated by measuring the reflection wavelength. These features make our strategy potentially useful in preparation of materials with low COF and extending the application of photonic hydrogels, including ocular drug delivery and monitoring systems, as well as articular tissue-mechanical sensors.

Dual-functional borosilicate glass (BSG) delivery implant for osteomyelitis treatment and bone regeneration

Effective treatment of osteomyelitis remains to be clinical challenge due to the recurrent and persistent nature of the disease. Studies have shown that borate glasses can serve as implants for local drug delivery in treating osteomyelitis, as well as aid in regenerating bone defects in vivo. However, both the kinetics of drug release from borate glass-based implants and the underlying molecular mechanism for promoting bone regeneration remain unclear. Here, delivery implants with varying amounts of antibiotics were fabricated by encapsulating gentamicin sulfate (GS) into a chitosan glue and applying it to borosilicate glass (BSG). Upon immersion in phosphate buffered saline (PBS), delivery implants degraded and converted into hydroxyapatite (HA). All delivery implants released GS sustainably over a period of around 25 days in both PBS and K2HPO4 solutions and displayed efficacious inhibition of E. coli and S. aureus in vitro. GS release occurred through diffusion for inhibition whereby Fickian diffusion was revealed to be the predominant release kinetic. Ions (B, Ca, P and Si) released from BSG supported the proliferation, differentiation, osteogenic gene expression and protein secretion of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. When implanted in a rabbit tibial osteomyelitis model, osteomyelitis in the experimental group with delivery implants was effectively cured. Meanwhile, delivery implants have significant osteogenesis-promoting effects after implantation time of 12-weeks in vivo. Implantation of BSG-based drug delivery implants developed in this study may provide a promising method for treating osteomyelitis as well as for facilitating efficient bone regeneration.

Self-expanding PMMA composite bone cement with sustained release of gentamicin sulfate and alendronate using water absorption pathways

Although drug-loaded polymethyl methacrylate (PMMA) bone cement had been widely used in the vertebroplasty and arthroplasty, the mismatch between the drug release cycle and clinical demand, as well as low drug release rate and single therapeutic effect restricted the use of PMMA bone cement as the drug carrier in clinical applications. In this study, poly(methyl methacrylate-acrylic acid)-alendronate [P(MMA-AA)-ALN] drug-loaded nanoparticles with anti-osteoporosis function were synthesized and introduced into the gentamicin sulfate (GS) loaded PMMA bone cement. The rapidly expandable bone cement with water absorption pathways was constructed by adjusting the particle size of P(MMA-AA)-ALN nanoparticles. More importantly, the sustained release of GS and ALN were creatively achieved by their migration through the water absorption pathways composed of P(MMA-AA)-ALN nanoparticles. The results showed that the cumulative release ratios of GS and ALN in the composites were up to 74.67 ± 1.02 % and 75.23 ± 1.96 %. Meanwhile, the release cycles of GS and ALN were extended to 4 weeks and 15 weeks, effectively preventing infection, and matching the normal bone healing cycle. In addition, the swelling and dual drug release bone cement (SDBC) displayed superior antibacterial activity and biocompatibility.

Gelatin/gentamicin sulfate-modified PMMA bone cement with proper mechanical properties and high antibacterial ability

With the aging of the population, the risk of osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis increases rapidly. Surgeons often fill the bone defect with injectable polymethylmethacrylate (PMMA) bone cement through vertebroplasty. However, compared with cancellous bone, the higher mechanical properties of PMMA bone cement can easily lead to the fracture of the adjacent cone. Besides, the wound infection caused by surgery is also a serious problem. In order to solve these problems, we designed a new type of PMMA bone cement, by adding gelatin as a pore former, 5% (w/w) gentamicin sulfate (GS) for antibacterial purpose, and 30% (w/w) barium sulfate (BaSO4) to provide excellent radiopacity. Compared with the traditional PMMA bone cement, with the dissolution of gelatin after being immersed in phosphate buffered saline (PBS) for 14 d, the mechanical properties of modified PMMA bone cement decreased by approximately 67%, which is close to the human cancellous bone. Besides, the release of GS increased 3.8 times, and the GS concentration remained above the minimum inhibitory concentration (MIC) for 12 d. In addition, the setting properties, contact angle, antibacterial ability, and cell compatibility of PMMA bone cement also maintained well. The integration and dissolution of gelatin were observed by a scanning electron microscope (SEM). All results indicate that the new type of gelatin-modified PMMA bone cement is a potential candidate material for vertebroplasty.

Self-Expanding Pmma Composite Bone Cement with Sustained Release of Gentamicin Sulfate and Alendronate Using Water Absorption Pathways

Self-Expanding Pmma Composite Bone Cement with Sustained Release of Gentamicin Sulfate and Alendronate Using Water Absorption Pathways

Long-term induction of endogenous BMPs growth factor from antibacterial dual network hydrogels for fast large bone defect repair

Osteoinductive, osteoconductive, and antibacterial properties of bone repair materials play important roles in regulating the successful bone regeneration. In the present work, we developed pH-sensitive gelatin methacryloyl (GelMA)-oxidized sodium alginate (OSA) hydrogels for dual-release of gentamicin sulfate (GS) and phenamil (Phe) to enhance the antibacterial activity and to promote large bone defect repair. Controlled release of GS was achieved through physical blending with GelMA-OSA solution before photo-polymeriaztion, while Phe was encapsulated into mesoporous silicate nanoparticles (MSN) within the hydrogels. In vitro antibacterial studies against Staphylococcus aureus and Escherichia coli indicated the broad-spectrum antibacterial property. Moreover, in vitro cell tests verified the synergistically enhanced osteogenic differentiation ability. Furthermore, in vivo studies revealed that the hydrogels significantly increased new bone formation in a critical-sized mouse cranial bone defect model. In summary, the novel dual-network hydrogels with both antibacterial and osteoinductive properties showed promising potential applications in bone tissue engineering.

Preparation of Cross-linked Chitosan Quaternary Ammonium Salt Hydrogel Films Loading Drug of Gentamicin Sulfate for Antibacterial Wound Dressing.

Hydrogels, possessing high biocompatibility and adaptability to biological tissue, show great usability in medical applications. In this research, a series of novel cross-linked chitosan quaternary ammonium salt loading with gentamicin sulfate (CTMCSG) hydrogel films with different cross-linking degrees were successfully obtained by the reaction of chitosan quaternary ammonium salt (TMCS) and epichlorohydrin. Fourier transform infrared spectroscopy (FTIR), thermal analysis, and scanning electron microscope (SEM) were used to characterize the chemical structure and surface morphology of CTMCSG hydrogel films. The physicochemical property, gentamicin sulphate release behavior, cytotoxicity, and antibacterial activity of the CTMCSG against Escherichia coli and Staphylococcus aureus were determined. Experimental results demonstrated that CTMCSG hydrogel films exhibited good water stability, thermal stability, drug release capacity, as well as antibacterial property. The inhibition zone of CTMCSG hydrogel films against Escherichia coli and Staphylococcus aureus could be up to about 30 mm. Specifically, the increases in maximum decomposition temperature, mechanical property, water content, swelling degree, and a reduction in water vapor permeability of the hydrogel films were observed as the amount of the cross-linking agent increased. The results indicated that the CTMCSG-4 hydrogel film with an interesting physicochemical property, admirable antibacterial activity, and slight cytotoxicity showed the potential value as excellent antibacterial wound dressing.

Dual-functionalized titanium for enhancing osteogenic and antibacterial properties

Bacterial infection and poor osseointegration of titanium implants are two of the main issues hindering their use in clinical applications. In order to solve these problems simultaneously, TiO2 nanotubes were fabricated, loaded with naringin (NA) and covered by gentamicin sulfate (GS)-inserted chitosan/gelatin bilayers through layer by layer technique. The successful system of the bifunctional titanium substrate was confirmed via scanning electron microscopy, atomic force microscope, water contact angle measurement, X-ray photoelectron spectroscopy and in vitro release of NA and GS. The multilayer-coated NA-loaded TiO2 nanotubes exhibited good biocompatibility as shown by cell morphology, cell viability assay, alkaline phosphatase activity, mineralization and qRT-PCR analysis of the osteogenesis related genes. Antibacterial experiments examining S. aureus and E. coli in vitro demonstrated that the bifunctional TiO2 nanotubes had antibacterial capabilities. Ihis approach provides a new and feasible strategy for improving the properties of titanium implants to promote osteogenic and antibacterial activity.

Hydrogels of Acryloyl guar gum-g-(acrylic acid-co-3sulfopropylacrylate) for high-performance adsorption and release of gentamicin sulphate

Hydrogels of Acryloyl guar gum-g-(acrylic acid-co-3sulfopropylacrylate) for high-performance adsorption and release of gentamicin sulphate

In Vitro Evaluation of Crosslinked Polyvinyl Alcohol/Chitosan – Gentamicin Sulfate Electrospun Nanofibers

Polymeric nanofibers with good antimicrobial properties are a promising option to thwart wound infection and accelerate wound healing. Although PVA/Chitosan possesses many useful properties, its antibacterial activity is insufficient for effective wound dressing. Therefore, using a hydrophilic drug such as Gentamicin Sulfate (GS) that has a broad-spectrum activity against a wide range of bacteria can enhance the nanofibers’ performance. In this study, polyvinyl alcohol (PVA) with chitosan nanofibers loaded with gentamicin sulfate was prepared using an electrospinning technique and crosslinked with glutaraldehyde for better loading efficiency and controlled drug release at the site of interest. Morphological investigation carried out using scanning electron microscopy showed smooth and homogeneous nanofibers. FT-IR was used to confirm the structure of the nanofibers. In situ crosslinking enabled penetration of the crosslinking agent into the nanofibers and improved the thermal stability and drug release performance. The thermal stability of PVA/Chitosan nanofibers was reduced with the addition of gentamicin sulfate. The kinetic release of gentamicin sulfate followed the Korsmeyer-Peppas model with release exponent, n < 0.5. Antibacterial testing of crosslinked nanofibers against Escherichia coli and Staphylococcus aureus showed good inhibition of bacterial growth. Crosslinked PVA/Chitosan nanofibers loaded with gentamicin sulfate showed multifunctional characteristics and thus may be a suitable material for controlled drug delivery and tissue engineering applications.

Hemostatic wound dressings based on drug loaded electrospun PLLA nanofibrous mats

Novel wound dressings were prepared using electrospun nanofibrous PLLA mats loaded with aluminum chloride (AlCl3), gentamicin sulphate (GS) and/or lidocaine hydrochloride (LHc) as a hemostatic, antibiotic, and local anesthetic drug, respectively. Structural characterization of the prepared mats was performed using FTIR spectroscopy, whereas morphological characteristics were determined using SEM micrographs of the fibers. For mats loaded with AlCl3, the majority of the fibers diameters were in the range [400–500 nm]. The wettability of the mats was investigated using contact angles method. Hemostasis tests have shown that all the prepared mats have better hemostatic efficiency than gauze bandage. However, mats loaded with only AlCl3 30%w/w have the best hemostatic performance with a decrease in blood clotting time of 80% and an increase in blood absorption capacity of 178% in comparison with gauze bandage. GS release kinetics in PBS solution was investigated. The experimental results showed that the release kinetics follows Korsmeyer-Peppas model with a correlation factor R2 = 0.999 and n = 0.1.

Polylactide/Polyvinylalcohol-Based Porous Bioscaffold Loaded with Gentamicin for Wound Dressing Applications.

This study explores the feasibility of modifying the surface liquid spraying method to prepare porous bioscaffolds intended for wound dressing applications. For this purpose, gentamicin sulfate was loaded into polylactide-polyvinyl alcohol bioscaffolds as a highly soluble (hygroscopic) model drug for in vitro release study. Moreover, the influence of inorganic salts including NaCl (10 g/L) and KMnO4 (0.4 mg/L), and post-thermal treatment (T) (80 °C for 2 min) on the properties of the bioscaffolds were studied. The bioscaffolds were characterized by scanning electron microscopy, Fourier Transform infrared spectroscopy, and differential scanning calorimetry. In addition, other properties including porosity, swelling degree, water vapor transmission rate, entrapment efficiency, and the release of gentamicin sulfate were investigated. Results showed that high concentrations of NaCl (10 g/L) in the aqueous phase led to an increase of around 68% in the initial burst release due to the increase in porosity. In fact, porosity increased from 68.1 ± 1.2 to 94.1 ± 1.5. Moreover, the thermal treatment of the Polylactide-polyvinyl alcohol/NaCl (PLA-PVA/NaCl) bioscaffolds above glass transition temperature (Tg) reduced the initial burst release by approximately 11% and prolonged the release of the drug. These results suggest that thermal treatment of polymer above Tg can be an efficient approach for a sustained release.

Electrospun composite fibers of PLA/PLGA blends and mesoporous silica nanoparticles for the controlled release of gentamicin sulfate

With the objective of developing a localized gentamicin sulfate (GS) delivery system with a controlled release kinetics for the prevention/management of osteomyelitis, composite electrospun fibers composed of poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) blends and GS loaded mesoporous silica nanoparticles (npSiGS) were prepared (PLA/PLGA: 1:3, 1:1, 3:1 w/w). GS was loaded into silica nanoparticles by adsorption, using a concentrated GS solution, and npSiGS were dispersed in the polymer solutions and immobilized in the polymeric matrix by occlusion, during fibers formations. For comparison, non-composite fibers with the same blend compositions containing GS simply dispersed in the polymeric phase were also produced. GS loaded nanoparticles were characterized by nitrogen adsorption/desorption isotherms and GS loading was quantified by thermogravimetric analysis. The morphology of the electrospun fibers, assessed by SEM, revealed that npSiGS were embedded along the composite fibers, some in the form of small aggregates. In vitro release studies showed that composite fibers exhibited lower initial burst releases and slower release kinetics, dependent on blend composition. Composite fibers with PLGA as the major component (25PLA-npSiGS) had the fastest release kinetics, while fibers with equal amounts of both polymers (50PLA-npSiGS) or with PLGA as the minor component (75PLA-npSiGS) had slower release kinetics, with constant GS release rates after the first day. These results suggest that PLA/PLGA blend composition can be manipulated to obtain composite fibers with a controlled and tailored GS release for at least three weeks. Finally, the antibacterial effect against Staphylococcus aureus of all produced fibers containing GS was confirmed by a disk diffusion method.

Photoresponsive Vesicles Enabling Sequential Release of Nitric Oxide (NO) and Gentamicin for Efficient Biofilm Eradication.

The development of new antibacterial agents that can efficiently eradicate biofilms is of crucial importance to combat persistent and chronic bacterial infections. Herein, the fabrication of photoresponsive vesicles capable of the sequential release of nitric oxide (NO) and gentamicin sulfate (GS) is reported, which can not only efficiently disperse Pseudomonas aeruginosa (P. aeruginosa) PAO1 biofilm but also kill the planktonic bacteria. Well-defined amphiphilic diblockcopolymers of poly(ethylene oxide)-b-poly(4-((2-nitrobenzyl)(nitroso)amino)benzyl methacrylate) (PNO) is first synthesized through atom transfer radical polymerization (ATRP). The PNO diblock copolymer self-assembled into vesicles in aqueous solution, and a hydrophilic antibiotic of GS is subsequently encapsulated into the aqueous lumens of vesicles. The vesicles undergo visible light-mediated N-NO cleavage, releasing NO and disintegrating the vesicles with the release of the GS payload. The sequential release of NO and GS efficiently eradicate P. aeruginosa PAO1 biofilm and kill the liberated bacteria, showing a better antibiofilm effect than that of NO or GS alone.

Influence of cross-linkers on the properties of cotton grafted poly (acrylamide-co-acrylic acid) hydrogel composite: swelling and drug release kinetics

Cross-linker plays a crucial role in monitoring water holding and drug release properties of a hydrogel system, an essential requirement for smart wound dressings. Present study is focused on the influence of cross-linkers poly ethylene glycol (PEG) and N,Nʹ-methylene bisacrylamide (MBAAm) on the properties of poly (acrylamide-co-acrylic acid) hydrogel grafted over the cotton fabric to form composite for medicated dressings. Fourier transform infrared spectroscopy (FTIR) confirms the grafting of hydrogel on the cotton fabric. Uniform hydrogel layer on the cotton surface is obtained under scanning electron microscopy (SEM). Swelling of the composite prepared using PEG follow first-order kinetics at acidic and neutral pH whereas second-order kinetic model at pH 8.5 while that prepared using MBAAm follow second-order kinetic equation at all the pHs studied. The swelling kinetics is also governed by Peppas model at all pHs. Release of gentamicin sulphate from both the composites are studied in phosphate buffers having pH 4.5, 7 and 8.5 at 37 ± 0.1 °C and observed that it is fastest in phosphate buffer having pH 7. On fitting drug release data into Peppas model, first and second-order kinetic equations, it is found that drug release is diffusion controlled and follows Fickian diffusion mechanism in case of the composite prepared by using PEG as cross-linker, whereas it is controlled by diffusion as well as chain relaxation in case of the composite prepared by using MBAAm. Mechanical testing using universal testing machine supports a higher mechanical strength of the hydrogel composite as compared to its film.

Gentamicin encapsulated within a biopolymer for the treatment of Staphylococcus aureus and Escherichia coli infected skin ulcers

Skin wound infection requires carefully long-term treatment with an immense financial burden to healthcare systems worldwide. Various strategies such as drug delivery systems using polymer matrix from natural source have been used to enhance wound healing. Natural rubber latex (NRL) from Hevea brasiliensis has shown angiogenic and tissue repair properties. Gentamicin sulfate (GS) is a broad-spectrum antibiotic which inhibits the growth of a wide variety of microorganisms and, because of this, it has also been applied topically for treatment of local infections. The aim of this study was to develop a GS release system using NRL as matrix for Staphylococcus aureus and Escherichia coli infected skin ulcers treatment, without changing drug antibiotic properties. The matrix did not change the GS antimicrobial activity against S. aureus and E. coli strains. Moreover, the NRL-GS biomembrane did not exhibit hemolytic activity, being non-toxic to red blood cells. The eluates of NRL-GS biomembranes and GS solutions did not significantly reduce the survival of Caenorhabditis elegans worms for 24 h at any of the tested concentrations. Thus, these results emphasize that the NRL-GS biomembrane proved to be a promising biomaterial for future studies on the development of dressings for topical uses, inexpensive and practicable, keeping drug antibiotic properties against pathogens and to reduce the side effects.

A pH and hyaluronidase dual-responsive multilayer-based drug delivery system for resisting bacterial infection

In this work, we developed an antibacterial drug-controlled release multilayer surface based on a layer-by-layer (LBL) assembly of polyacrylic acid (PAA) and chitosan quaternary ammonium salt (QCS). Gentamicin sulfate (GS) is incorporated into the multilayer and hyaluronic acid (HA) is utilized as the topmost layer as a sealing layer. During the bacterial attack, the pH of the microenvironment slightly rises, which makes the multilayer swell and promotes the release of drugs. Meanwhile, the hyaluronidase (HAase) secreted by bacteria triggers the degradation of the HA layer and further accelerates the GS release to fulfill its antibacterial activity. The surface showed high antibacterial activity against S. aureus and E. coli with pH and enzyme dual-responsive drug delivery at an accurate time. The intelligent antibacterial surface presented in this study shows promising potential in application to infection-resistance medical devices.

In Vivo Wound Healing Performance of Halloysite Clay and Gentamicin-Incorporated Cellulose Ether-PVA Electrospun Nanofiber Mats.

Wound healing is a dynamic and complex process that requires a suitable environment to enhance the rapid healing process. In this context, fabrications of nanofibrous materials with antibiotic and antibacterial properties are becoming extremely important. In this present work, we report on the fabrication and characterization of electro-spun cellulose ether-PVA nanofiber mats loaded with halloysite clay (HNT) and gentamicin sulfate (GS) for faster wound healing applications. The morphology of nanofiber mats was examined by SEM and TEM. The average diameter of the nanofiber mats were in the range of 325 ± 30 nm. The physicochemical characterizations were done by FT-IR and XRD, which reveal the presence of HNT and GS into the nanofibers. The incorporation of halloysite gave good mechanical strength to the nanofiber mats. Swelling studies indicated the hydrophilicity of the mats. In vitro studies revealed that HNTs are nontoxic to L929 fibroblast cells and also promote cell growth and proliferation. The antibacterial property of HNT was also studied. The slow release of GS from the nanofiber mats was observed for a period of 18 days. The in vivo wound healing studies on the wistar rats for 21 days revealed the wound healing faster within 2 weeks by the incorporation of HNT and GS into the nanofiber mats and hence these nanofiber mats show great potential in acute and chronic wound healing applications.

Chemical grafting of antibiotics into multilayer films through Schiff base reaction for self-defensive response to bacterial infections

Pathogenic bacteria can easily adhere to implanted biomaterials, and this is followed by rapid propagation and biofilm formation. In intravenous prophylactic administration and general topical administration based on physical or non-covalent bonding of antibiotics it is difficult to prevent low concentration release and excessive release, which lead to the development of drug-resistant bacteria. In this work, gentamicin sulfate (GS) was grafted onto aldylated sodium alginate (al-ALG) through dynamic chemical covalent bonding via a Schiff base reaction between aldehyde and amino groups. Antibiotic-loaded sodium alginate was coated on biomaterials by self-assembly with positively charged poly(ethyleneimine) (PEI) to form multilayer films. The ALG-GS/PEI multilayer films showed high antibiotic-loading capacities (223 μg/cm2) through dynamic chemical bonding. The release of GS gave bacterial infection self-defensive features. GS release was much faster at pH 5.5 than at pH 7.4. In vitro antibacterial tests, namely bacterial live/dead staining, zone of bacterial inhibition, and shake-flask culture methods showed efficient bactericidal activity with Staphylococcus aureus and Escherichia coli as model bacteria. ALG-GS/PEI multilayer films killed more than 99.99% of bacteria after 24 h incubation. These antibiotic-loaded multilayer films with long-term, self-defensive, smart bacterial infection and biofilm inhibition properties were almost totally resistant to biofilm development after 72 h incubation. The advantages of chemically grafting antibiotics are reflected in the maintenance of inhibition zone size after storage in a simulated body fluid environment. Dynamic chemical bonding of antibiotics in multilayer films has promising potential applications in biomaterial surface modification.