methylcellulose and Staphylococcal-Infections

This article reports on comparative in vitro characterization and in vivo evaluation of pre-formed cellulose-based gels, methylcellulose (MC) and carboxymethylcellulose sodium (CMC) and in situ gel-forming Pluronic F127 (PL) for ocular delivery of ciprofloxacin hydrochloride (Cipro) by using a bacterial keratitis model and histological corneal examination. Drug-polymer interactions were studied employing thermal analysis. Further, different concentrations (1-3% w/w or 10-30% w/w) of gels depending on the nature of the polymer used were prepared, characterized for clarity, pH, rheology and in vitro release. Selected gel formulations were evaluated for ocular delivery to Staphylococcus aureus-infected rabbit corneas; and ocular toxicity through histological examination of the cornea. The results demonstrated no Cipro-polymers physicochemical interactions and pseudoplastic flow for all gels used at 35 °C. Both polymer concentrations and drug solubility in the gels are dominantly the rate-determining factors for in vitro drug release. The corneal healing rate for all gel-based formulations was significantly faster (p < 0.05) than that for Cipro solution-treated rabbits. PL-based gel induced significant swelling/edema of the corneal stroma, compared with MC- and CMC-based gels. In conclusion, cellulose-based polymers have superior ocular tolerability/dramatically less irritant; and superior efficacy with more convenient administration compared with PL and Cipro solution, respectively.

Topics: Animals; Anti-Bacterial Agents; Carboxymethylcellulose Sodium; Ciprofloxacin; Cornea; Delayed-Action Preparations; Female; Gels; Keratitis; Male; Methylcellulose; Poloxamer; Rabbits; Rheology; Staphylococcal Infections; Staphylococcus aureus; Viscosity

Infections of bone and joint tissues following arthroplasty surgeries remain a major challenge in orthopaedic settings. Methicillin resistant Staphylococcus aureus (MRSA) is recognised as an established pathogen in such infections. Combination therapy using linezolid and bacteriophage impregnated in biopolymer was investigated in the present study as an alternative strategy to prevent MRSA colonisation on the orthopaedic implant surface.. Coating of stainless steel orthopaedic grade K-wires was achieved using hydroxypropylmethlycellulose (HPMC) mixed with phage alone, linezolid alone and phage and linezolid together. The potential of these agents to inhibit adhesion of S.aureus (MRSA) 43300 on K-wires was assessed. Coated and naked wires were analysed by scanning electron microscopy (SEM) and fluorescent staining.. Significant reduction in bacterial adhesion was achieved on phage/linezolid wires in comparison to naked as well as HPMC coated wires. However, maximum reduction in bacterial adherence (∼4 log cycles) was observed on the wires coated with phage-linezolid combination. The frequency of emergence of resistant mutants was also negligible in presence of both the agents.. This study provides evidence to confirm that local delivery system employing linezolid (a potent protein synthesis inhibitor) along with a broad spectrum lytic bacteriophage (capable of self-multiplication) is able to attack the adhered as well as surrounding bacteria present near the implant site. Unlike other antibiotic based therapies, this combination has the potential to significantly restrict the emergence of resistant mutants, thus paving the way for effective treatment of MRSA associated infection of medical implants.

Topics: Acetamides; Analysis of Variance; Arthroplasty; Bacteriophages; Bone Wires; Combined Modality Therapy; Fluorescence; Humans; Hypromellose Derivatives; Linezolid; Methicillin-Resistant Staphylococcus aureus; Methylcellulose; Microscopy, Electron, Scanning; Oxazolidinones; Staphylococcal Infections

The use of catheters and other implanted devices is constantly increasing in modern medicine. Although catheters improve patients' healthcare, the hydrophobic nature of their surface material promotes protein adsorption and cell adhesion. Catheters are therefore prone to complications, such as colonization by bacterial and fungal biofilms, associated infections, and thrombosis. Here we describe the in vivo efficacy of biologically inspired glycocalyxlike antiadhesive coatings to inhibit Staphylococcus aureus and Pseudomonas aeruginosa colonization on commercial totally implantable venous access ports (TIVAPs) in a clinically relevant rat model of biofilm infection. Although noncoated TIVAPs implanted in rats were heavily colonized by the 2 biofilm-forming pathogens with a high percentage of occlusion, coating TIVAPs reduced their initial adherence and subsequently led to 4-log reduction in biofilm formation and reduced occlusion. Our antiadhesive approach is a simple and generalizable strategy that could be used to minimize clinical complications associated with the use of implantable medical devices.

Topics: Animals; Bacterial Adhesion; Biofilms; Biomimetic Materials; Catheter-Related Infections; Central Venous Catheters; Glycocalyx; Male; Methylcellulose; Pseudomonas Infections; Rats; Staphylococcal Infections

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) poses an infection risk and eradication during hospitalization is recommended. Bacteriophage therapy may be effective in this scenario but suitable nasal formulations have yet to be developed. Here we show that lyophilization of bacteriophages in 1ml of a viscous solution of 1-2% (w/v) hydroxypropyl methylcellulose (HPMC) with/without the addition of 1% (w/v) mannitol, contained in Eppendorf tubes, yields nasal inserts composed of a highly porous leaflet-like matrix. Fluorescently labeled bacteriophage were observed to be homogenously distributed throughout the wafers of the dried matrix. The bacteriophage titer fell 10-fold following lyophilization to 10(8)pfu per insert, then falling a further 100- to 1000-fold over 6 to 12months storage at 4°C. This compares well with a total dose of 6×10(5)pfu in 0.2ml liquid applied into the ear during a recent clinical trial in humans. The residual water content of the lyophilized inserts was reduced upon the addition of mannitol to HPMC, but this did not have any correlation to the lytic activity. Mannitol underwent a transition from its amorphous to crystalline state during exposure of the inserts to increasing relative humidities (as would be experienced in the nose), although this transition was suppressed by higher HPMC concentrations and the presence of buffer containing gelatin and bacteriophages. Our results therefore suggest that lyophilized inserts harboring bacteriophage selective for S. aureus may be a novel means for the eradication of MRSA resident in the nose.

Topics: Absorption; Administration, Intranasal; Chemistry, Pharmaceutical; Drug Implants; Freeze Drying; Humans; Hypromellose Derivatives; Mannitol; Methicillin-Resistant Staphylococcus aureus; Methylcellulose; Staphylococcal Infections; Streptococcus Phages; Surface Properties; Water

The study was aimed at design of new dosage forms of doxorubicin (films, erythrocyte vehicles) for correction of its hepatotoxic, prooxidant and immunosuppressory effects. The experiments were performed on Wistar rats with the use of doxorubicin of Lens-Pharm (Moscow) and auxiliary substances meeting the requirements of the standards. Technology for preparation of doxorubicin-entrapped films was developed and the optimal polymer for the vehicle was recommended, i.e. oxypropylmethylcellulose Methocel 65 Hg 50 providing preservation of the antimicrobial activity. Conditions for storage of the antibiotic-entrapped films were determined. The main qualitative indices of the antibiotic-entrapped films were shown to be stable during the storage for 12 months. Erythrocyte-vehicles with entrapped doxorubicin were prepared. Antibiotic-free erythrocyte vehicles were found to preserve their ability to entrap doxorubicin for 9 days and the doxorubicin-entrapped erythrocyte vehicles were stable for 48 hours. A procedure for spectrophotometric qualitative evaluation of doxorubicin entrapping into the films and erythrocyte vehicles was developed. It was observed that administration of doxorubicin immobilized in the films had a stabilizing effect on the immunity status, the level of lipid peroxidation, the potency of the antioxidant system, cytolysis and cholestasis. Administration of the doxorubicin entrapped in the erythrocyte vehicles stimulated the body immune response, normalized the indices of the lipid peroxidation--antioxidant system and the state of the hepatic cells in the laboratory animals infected by staphylococci.

Topics: Animals; Doxorubicin; Drug Carriers; Drug Evaluation, Preclinical; Drug Stability; Erythrocyte Membrane; Hepatocytes; Immunosuppression Therapy; Injections, Intramuscular; Lipid Peroxidation; Methylcellulose; Pharmaceutic Aids; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Topics: Administration, Topical; Anti-Inflammatory Agents; Chloramphenicol; Humans; Keratoconjunctivitis; Lacrimal Apparatus; Methylcellulose; Mucus; Ophthalmic Solutions; Prednisolone; Staphylococcal Infections; Xerophthalmia

Topics: Anesthetics; Autoimmune Diseases; Bicarbonates; Chloramphenicol; Cysteine; Dextrans; Heparin; Herpesviridae Infections; Humans; Hydroxychloroquine; Idoxuridine; Keratoconjunctivitis; Lacrimal Apparatus; Lupus Erythematosus, Systemic; Methylcellulose; Oils; Paraffin; Rheumatic Diseases; Sodium Chloride; Staphylococcal Infections; Steroids; Surface-Active Agents; Tears; Thyroxine; Vitamin A