Release Of Streptomycin Research Articles

Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers.

The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles’ crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties.

Preparation and Characterization of Aminoglycoside-Loaded Chitosan/Tripolyphosphate/Alginate Microspheres against E. coli.

Although aminoglycosides are one of the common classes of antibiotics that have been widely used for treating infections caused by pathogenic bacteria, the evolution of bacterial resistance mechanisms and their inherent toxicity have diminished their applicability. Biocompatible carrier systems can help sustain and control the delivery of antibacterial compounds while reducing the chances of antibacterial resistance or accumulation in unwanted tissues. In this study, novel chitosan gel beads were synthesized by a double ionic co-crosslinking mechanism. Tripolyphosphate and alginate, a polysaccharide obtained from marine brown algae, were employed as ionic cross-linkers to prepare the chitosan-based networks of gel beads. The in vitro release of streptomycin and kanamycin A was bimodal; an initial burst release was observed followed by a diffusion mediated sustained release, based on a Fickian diffusion mechanism. Finally, in terms of antibacterial properties, the particles resulted in growth inhibition of Gram-negative (E. coli) bacteria.

Non-phytotoxic zinc based nanoparticle adjuvant for improving rainfastness and sustained release of streptomycin

Antibiotic streptomycin has been extensively used for the treatment of bacterial infections in humans. Streptomycin is also used in agriculture to protect pome fruits from fire blight, a destructive bacterial disease. Recently, streptomycin sulfate (65.8 % A.I.) has been labeled for suppression of Huanglongbing in Florida, USA. The A.I. is water soluble and therefore suffers from poor rainfastness after foliar application. Due to high polarity, uptake and mobility of streptomycin sulfate through phloem vascular system is limited. Furthermore, streptomycin is prone to UV degradation when exposed to direct sunlight. Therefore, an efficient adjuvant is desired to improve rainfastness, UV-stability and vascular mobility. In this study, a novel non-phytotoxic zinc sulfide (ZnS) nanoparticle based adjuvant has been introduced that demonstrates improved rainfastness and sustained release of streptomycin. Antibacterial efficacy of streptomycin and the ZnS-streptomycin conjugate was found comparable when tested against model plant pathogenic bacteria (E. coli, X. alfalfae, and P. syringae).

Synthesis and Characterization of Nanohydroxyapatite-Gelatin Composite with Streptomycin as Antituberculosis Injectable Bone Substitute.

The most effective treatment for spinal tuberculosis was by eliminating the tuberculosis bacteria and replacing the infected bone with the bone graft to induce the healing process. This study aims to synthesize and characterize nanohydroxyapatite-gelatin-based injectable bone substitute (IBS) with addition of streptomycin. The IBS was synthesized by mixing nanohydroxyapatite and 20 w/v% gelatin with ratio of 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, and 75:25 ratio and streptomycin addition as antibiotic agent. The mixture was added by hydroxypropyl methylcellulose as suspending agent. FTIR test showed that there was a chemical reaction occurring in the mixture, between the gelatin and streptomycin. The result of injectability test showed that the highest injectability of the IBS sample was 98.64% with the setting time between 30 minutes and four hours after injection on the HA scaffold that represents the bone cavity and coat the pore scaffold. The cytotoxicity test result showed that the IBS samples were nontoxic towards BHK-21 fibroblast cells and human hepatocyte cells since the viability cell was more than 50% with significant difference (p-value<0.05). The acidity of the IBS was stable and it was sensitive towards Staphylococcus aureus with significantly difference (p-value<0.05). The streptomycin release test showed that the streptomycin could be released from the IBS-injected bone scaffold with release of 2.5% after 4 hours. All the results mentioned showed that IBS was suitable as a candidate to be used in spinal tuberculosis case.

Hydroxyapatite Nanocrystal Deposited Titanium Dioxide Nanotubes Loaded with Antibiotics for Combining Biocompatibility and Antibacterial Properties

ABSTRACTHydroxyapatite (HA)/nanotubular titanium dioxide (TiO2) composite coatings loaded with antibiotics were developed to combine biocompatibility and antibacterial property. TiO2 nanotubes were first fabricated on Ti plates using anodization techniques. Then HA nanocrystals were synthesized on the TiO2 nanotubes by electrochemical deposition, followed by loading of a model drug compound, streptomycin. The streptomycin release profile of the composite coating was investigated. Bacterial tests demonstrate that the streptomycin-loaded composite coatings were highly effective in inhibiting bacterial growth. Simulated body fluid (SBF) experiments indicated that the composite coatings possessed good osseointegration capability.

Polymer-augmented liposomes enhancing antibiotic delivery against intracellular infections.

Pulmonary intracellular infections, such as tuberculosis, anthrax, and tularemia, have remained a significant challenge to conventional antibiotic therapy. Ineffective antibiotic treatment of these infections can lead not only to undesired side effects, but also to the emergence of antibiotic resistance. Aminoglycosides (e.g., streptomycin) have long been part of the therapeutic regiment for many pulmonary intracellular infections. Their bioavailability for intracellular bacterial pools, however, is limited by poor membrane permeability and rapid elimination. To address this challenge, polymer-augmented liposomes (PALs) were developed to provide improved cytosolic delivery of streptomycin to alveolar macrophages, an important host cell for intracellular pathogens. A multifunctional diblock copolymer was engineered to functionalize PALs with carbohydrate-mediated targeting, pH-responsive drug release, and endosomal release activity with a single functional polymer that replaces the pegylated lipid component to simplify the liposome formulation. The pH-sensing functionality enabled PALs to provide enhanced release of streptomycin under endosomal pH conditions (70% release in 6 hours) with limited release at physiological pH 7.4 (16%). The membrane-destabilizing activity connected to endosomal release was characterized in a hemolysis assay and PALs displayed a sharp pH profile across the endosomal pH development target range. The direct connection of this membrane-destabilizing pH profile to model drug release was demonstrated in an established pyranine/p-xylene bispyridinium dibromide (DPX) fluorescence dequenching assay. PALs displayed similar sharp pH-responsive release, whereas PEGylated control liposomes did not, and similar profiles were then shown for streptomycin release. The mannose-targeting capability of the PALs was also demonstrated with 2.5 times higher internalization compared to non-targeted PEGylated liposomes. Finally, the streptomycin-loaded PALs were shown to have a significantly improved intracellular antibacterial activity in a Francisella-macrophage co-culture model, compared with free streptomycin or streptomycin delivered by control PEGylated liposomes (13× and 16×, respectively). This study suggests the potential of PALs as a useful platform to deliver antibiotics for the treatment of intracellular macrophage infections.

Electrochemical growth of composite hydroxyapatite coatings for controlled release

An electrochemical method was used to load ionic molecules into hydroxyapatite (HA) coatings during electrochemical synthesis. A metal cathode surface was first electrochemically coated with a thin layer of HA. Then, a second electrochemical coating step was conducted with non-reactive ionic molecules added to the synthesis solution. The loading and release from the HA films are driven in large part by the sign and valence of charge on the ionic additive. Cationic additives are attracted to the cathode surface and effectively loaded to form composite HA films, while anionic species are repelled from the cathode and not effectively incorporated. Divalent cations are released more slowly than monovalent cations. This simple method may be used to create drug eluting bioactive coatings for controlled release. The loading and release of streptomycin, a common antibiotic, was measured as a representative pharmaceutical example.

Multifunctional Medicated Lyophilised Wafer Dressing for Effective Chronic Wound Healing

Wafers combining weight ratios of Polyox with carrageenan (75/25) or sodium alginate (50/50) containing streptomycin and diclofenac were prepared to improve chronic wound healing. Gels were freeze-dried using a lyophilisation cycle incorporating an annealing step. Wafers were characterised for morphology, mechanical and in vitro functional (swelling, adhesion, drug release in the presence of simulated wound fluid) characteristics. Both blank (BLK) and drug-loaded (DL) wafers were soft, flexible, elegant in appearance and non-brittle in nature. Annealing helped to improve porous nature of wafers but was affected by the addition of drugs. Mechanical characterisation demonstrated that the wafers were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed skin tissue. Differences in swelling, adhesion and drug release characteristics could be attributed to differences in pore size and sodium sulphate formed because of the salt forms of the two drugs. BLK wafers showed relatively higher swelling and adhesion than DL wafers with the latter showing controlled release of streptomycin and diclofenac. The optimised dressing has the potential to reduce bacterial infection and can also help to reduce swelling and pain associated with injury due to the anti-inflammatory action of diclofenac and help to achieve more rapid wound healing.

Functionalized Mesostructured Cellular Foams for Loading and Release of Streptomycin

Abstract Mesostructured cellular foam (MCF) materials were synthesized by microemulsion followed by functionalization with glucose or glutaraldehyde. Successful surface modification was confirmed by Fourier transform infrared, X-ray small-angle diffraction, and nitrogen sorption measurements. The effect of surface chemistry of MCF on the loading and release of streptomycin sulfate was studied in detail. Results indicated that grafting with either glucose or glutaraldehyde cannot only increase the loading amount of drug from 5% to 25% but also change the drug release profile significantly. This work provided an excellent example of controlling drug release by varying the surface chemistry of the materials.

In situ-ATR–FTIR analysis on the uptake and release of streptomycin from polyelectrolyte complex layers

In-situ ATR–FTIR spectroscopy and line shape analysis of the diagnostic spectral region was used to quantify the bound amount and release of the antibiotic streptomycin (STRP) at polyelectrolyte (PEL) multilayers (PEM) of poly(ethyleneimine) (PEI) and poly(acrylic acid) (PAA) or PEI and sodium alginate (ALG). Unlike common concepts based on the drug enrichment of the release medium, this analytical concept allowed to measure quantitatively the drug depletion in the delivery matrix. The measured kinetic in situ ATR–FTIR data were analysed by a modified Korsmeyer–Peppas equation based on two characteristic release parameters k and n.As main experimental parameters the number of PEL layers (adsorption steps) z and the STRP/PEL ratio were varied. For z=8 the STRP/PEL ratio showed the most significant influence on release kinetics, whereby for STRP/PEL=1:25 slowest (n=0.77) and lowest (k=21.4%) and for STRP/PEL=1:5 most rapid (n=0.30) and highest (k=58.6%) drug releases were found. PEM-PEI/ALG-8 (STRP/PEL=1:5) revealed slower release rates (n=0.58) and lower released STRP amounts (k=17.1%) compared to PEI/PAA. UV–VIS data on time dependent STRP enrichment of the release medium showed a similar trend compared to respective ATR–FTIR data on STRP depletion in PEM. Released amounts of around 1–2mg from the herein introduced PEM films could be determined. The introduced analytical concept will be used as screening tool for other drugs, drug eluting films and bone substituting materials.

Enhanced antibiotic multi‐resistance in nasal and faecal bacteria after agricultural use of streptomycin

Streptomycin is used in arboriculture to control fire blight. Using sheep as a model, multidrug-resistant bacteria in mammals were found to be selected after the intentional release of streptomycin into the environment. Escherichia coli and Staphylococcus spp. were isolated from the faeces and nasal cavities, respectively, of sheep grazing on a field sprayed with streptomycin at concentrations used in orchards (test group) and on a field without streptomycin (control group). Before the application of streptomycin, the percentage of streptomycin-resistant E. coli isolates in faeces was 15.8% in the control group and 14.7% in the test group. After the application of streptomycin, the overall number of streptomycin-resistant E. coli isolates was significantly higher in the test group (39.9%) than in the control group (22.3%). Streptomycin-resistant Staphylococcus isolates were only detected after the application of streptomycin. Streptomycin resistance was frequently associated with resistance to sulfamethoxazole, ampicillin, tetracycline and chloramphenicol and less frequently to cefotaxime in E. coli, and to tetracycline, fusidic acid and tiamulin in Staphylococcus spp. This study shows that the application of low concentrations of streptomycin on grass, as occurs during the spraying of orchards, selects for multidrug-resistant nasal and enteric bacterial flora, including extended-spectrum beta-lactamase-producing E. coli.

Factors influencing cryoprotective activity and drug leakage from liposomes after freezing

The effects of freezing and thawing conditions and cryoprotective additives on release of streptomycin from lecithin liposomes following freeze-thaw cycles have been investigated. Drug retention was maximized by slow cooling (approx. 1 degree C min-1). At temperatures between 0 degree and -20 degrees C, the extent of drug loss was time-dependent indicating incomplete freezing; below -45 degrees C this effect was abolished and the system was stable. Osmotic gradients across the liposome membrane during freezing were found to have little effect on drug loss. Marked cryoprotective activity was shown by dimethylsulphoxide, glycerol, alanine and glycinebetaine at concentrations of 3% w/v or less. At this concentration sucrose and mannitol had little activity.

The Business of Oncology 2010: What Is Ahead?

Wafers combining weight ratios of Polyox with carrageenan (75/25) or sodium alginate (50/50) containing streptomycin and diclofenac were prepared to improve chronic wound healing. Gels were freeze-dried using a lyophilisation cycle incorporating an annealing step. Wafers were characterised for morphology, mechanical and in vitro functional (swelling, adhesion, drug release in the presence of simulated wound fluid) characteristics. Both blank (BLK) and drug-loaded (DL) wafers were soft, flexible, elegant in appearance and non-brittle in nature. Annealing helped to improve porous nature of wafers but was affected by the addition of drugs. Mechanical characterisation demonstrated that the wafers were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed skin tissue. Differences in swelling, adhesion and drug release characteristics could be attributed to differences in pore size and sodium sulphate formed because of the salt forms of the two drugs. BLK wafers showed relatively higher swelling and adhesion than DL wafers with the latter showing controlled release of streptomycin and diclofenac. The optimised dressing has the potential to reduce bacterial infection and can also help to reduce swelling and pain associated with injury due to the anti-inflammatory action of diclofenac and help to achieve more rapid wound healing. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1720-1733, 2014

Streptomycin release from N,N-bis(2-hydroxyethyl) fatty amide modified polymeric coating

N,N-bis(2-hydroxyethyl) fatty amide (HAFA) derived from castor oil has been employed as an eco-friendly curing agent for poly(butyl methacrylate-co-maleic anhydride) based acrylic resin (BMA-MA). Coating compositions with varying ratio of BMA-MA/HAFA and streptomycin were prepared by dissolving the previously stated mixture in dimethyl formamide (DMF) with mechanical stirring. The films were prepared by applying the mixture on mild steel panels and then baked in oven at 150 °C for 30 min. Streptomycin release was examined by placing 1 in. 2 of the film in 100 mL of distilled water in stoppered flask in a rotary shaker. The amount of streptomycin release as a function of time was determined using spectrophotometer at 540 nm.

Synthesis of polyglutamine and dextran conjugates of streptomycin with an acid-sensitive drug-carrier linkage

A polymeric prodrug of streptomycin was prepared by coupling the drug via a spacer, glycine hydrazide, onto a polymeric carrier. In a first step, glycine N-Boc-hydrazide was linked to a 4-nitrophenyl chloroformate activated polymer. After removing the Boc group, streptomycin was coupled with the polymeric hydrazide with formation of a hydrazone bond. In order to target the drug-carrier derivative to the macrophages, 6-aminohexyl-α- D-mannopyranoside side groups were introduced. The polymeric streptomycin derivative was shown to be non hemolytic. The hydrolytic stability of the polymer-streptomycin conjugate was studied at physiological and lysosomal pH. Streptomycin release was found to be faster in the lysosomal pH range.