The wound healing and antibacterial potential of triple-component nanocomposite (chitosan-silver-sericin) films loaded with moxifloxacin.

AIM: The current study reports the development and evaluation of chitosan-sericin-silver nanocomposite (CSSN) films without and with moxifloxacin (Mox). METHODOLOGY: The film preparation method involved the in-situ synthesis of silver nanoparticles within the chitosan-sericin colloidal composite followed by preparation into a film by solvent casting technique. In-situ formation and the particle size analysis of the silver nanoparticles was performed via UV-Visible and zeta-size spectrometer. The prepared films were tested for swelling ratio, contents uniformity, in-vitro Mox release, and permeation analysis. The morphological (SEM), elemental (EDX), spectral (FT-IR), structural (XRD), and thermal (TGA and DSC) properties of the composites were also inspected. The antibacterial activity of the CSSN films was performed against seven pathogenic bacterial strains including five ATCC and two clinical strains. The potential wound healing activity of the composite films was evaluated on burn wound model induced in Sprague Dawley male rats. RESULTS: The prepared films displayed good swelling profile with a sustained in-vitro Mox release and permeation profile; attaining maximum of 78.57% (CSSM3) release and 55.05% (CSSM1) permeation (CSSM1) in 24 h. The prepared films, particularly the Mox-loaded CSSN films displayed a promising antibacterial activity against all the tested strains with the activity being highest against MRSA (clinical isolates). The prepared films indicated a remarkable wound healing applications with successful fibrosis, collagen reorganization, neovascularization, and mild epidermal regeneration after 7 days of treatment with no silver ions detection in animal's blood. CONCLUSION: The obtained findings strongly suggest the use of the prepared novel composite dressing for wound care applications.

Chemical synthesis of chitosan/silver nanocomposites films loaded with moxifloxacin: Their characterization and potential antibacterial activity.

This article reports moxifloxacin (Mox)-loaded nanocomposite films (CSN) of chitosan and chemically reduced silver (Ag). The synthesis of silver nanoparticles was confirmed by specific surface plasmon resonance (SPR) peaks detected via UV-Visible spectroscopy at the wavelength range of 400-450 nm. The embedded Mox was chemically characterized and kinetically analyzed for in-vitro drug release and ex-vivo drug permeation through rat skin. The prepared films presented higher swelling ratio and lower tensile strength (TS) and better elongation at break (EB) than control formulation (pure chitosan film). All the prepared Mox-loaded, non-crosslinked formulations presented sustained release of drug up to 12 h while slow and prolonged drug release up to 36 h was observed in Mox-loaded crosslinked CSN films. Drug permeation studies indicated that the maximum cumulative amount of Mox permeated (%) among Mox-loaded, non-crosslinked CSN films was displayed by CSM1 (57.79%); while in case of Mox-loaded, crosslinked CSN films, the highest drug permeation was presented by CSM18 (62.87%) in 24 h. The antibacterial efficacy of the prepared films was tested in-vitro against S. aureus (ATCC # 6538), P. aeruginosa (ATCC # 9721) and two clinically isolated strains of methicillin resistant S. aureus (MRSA). CSN films presented excellent against the all the selected strains with antibacterial potential being highest against S. aureus. In summary, the promising antibacterial potential of the CSN films recommend its biomedical application for use in wound dressing.

Facile Synthesis of Chitosan Based-(AMPS-co-AA) Semi-IPNs as a Potential Drug Carrier: Enzymatic Degradation, Cytotoxicity, and Preliminary Safety Evaluation.

OBJECTIVE: The study describes the development of chitosan-based (AMPS-co-AA) semi-IPN hydrogels using free radical polymerization technique. METHODS: The resulting hydrogels were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), X-Ray diffraction (XRD), and Scanning Electron Microscopy (SEM). The successful crosslinking of chitosan, 2- Acrylamido-2-Methylpropane Sulfonic Acid (AMPS), and Acrylic Acid (AA) was confirmed by FT IR. Unloaded and drug-loaded hydrogels exhibited higher thermal stability after crosslinking compared to the individual components. XRD confirmed the decrease in crystallinity after hydrogel formation and molecular dispersion of Oxaliplatin (OXP) in the polymeric network. SEM showed rough, vague and nebulous surface resulting from crosslinking and loading of OXP. RESULTS: The experimental results revealed that swelling and drug release were influenced by the pH of the medium being low at acidic pH and higher at basic pH. Increasing the concentration of chitosan and AA enhanced the swelling, drug loading and drug release while AMPS was found to act inversely. CONCLUSION: It was confirmed that the hydrogels were degraded more by specific enzyme lysozyme as compared to the non-specific enzyme collagenase. In-vitro cytotoxicity suggested that the unloaded hydrogels were non-cytotoxic while crude drug and drug-loaded hydrogel exhibited dose-dependent cytotoxicity against HCT-116 and MCF-7. Results of acute oral toxicity on rabbits demonstrated that the hydrogels are non-toxic up to 3900 mg/kg after oral administration, as no toxicity or histopathological changes were observed in comparison to control rabbits. These pH-sensitive hydrogels appear to provide an ideal basis as a safe carrier for oral drug delivery.

Chemical synthesis and characterization of chitosan/silver nanocomposites films and their potential antibacterial activity.

This study provides the optimum preparation parameters for functional chitosan silver nanocomposite (CSN) films with promising antibacterial efficacy though prepared with very low silver nitrate (AgNO3) concentration. Chitosan nano­silver composites were fabricated by In-situ chemical method utilizing the reducing ability of sodium borohydride (NaBH4) and afterward casted into films. Utilization of response surface methodology, NCSS, and SigmaPlot for the optimization of CSN and their predicted antibacterial efficacy assessment of the selected bacterial strains (standard and clinical) was the essential part of the study. The cumulative silver ions released from the CSN films was examined by AAS and was found pH dependent. The developed nanocomposite films exhibited strong antibacterial activity against ATCC strains of Gram-positive Staphylococcus aureus, Gram-negative bacteria (Pseudomonas aeruginosa) and clinically isolated strains of MRSA. The antibacterial activity CSN films were compared with three commercially available dressings (Aquacel Ag®, Bactigras®, and Kaltostat®) and Quench cream. Statistical analysis of the results indicated that the developed CSN films were equally or even more effective than commercial products. Thus the fabricated CSN films may act as a potential candidate to overcome the emerging antibiotic resistance particularly in hospital-acquired skin infections caused by MRSA.

Enhancement of Dissolution and Skin Permeability of Pentazocine by Proniosomes and Niosomal Gel.

Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the oral bioavailability, stability, and topical permeability of therapeutic agents. The low solubility and low oral bioavailability due to extensive first pass metabolism make Pentazocine as an ideal candidate for oral and topical sustained release delivery. The present study was aimed to formulate the PNs by quick slurry method that are converted to niosomes (liquid dispersion) by hydration, and subsequently formulated to semisolid niosomal gel. The PNs were found in spherical shape in the SEM and stable in the physicochemical and thermal analysis (FTIR, TGA, and XRD). The quick slurry method produced high recovery (> 80% yield) and better flow properties (θ = 28.1-37.4°). After hydration, the niosomes exhibited desirable entrapment efficiency (44.45-76.23%), size (4.98-21.3 µm), and zeta potential (- 9.81 to - 21.53 mV). The in vitro drug release (T100%) was extended to more than three half-lives (2-4 h) and showed good fit to Fickian diffusion indicated by Korsmeyer-Peppas model (n = 0.136-0.365 and R2 = 0.9747-0.9954). The permeation of niosomal gel was significantly enhanced across rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found promising candidates for oral as dissolution enhancement and sustained release for oral and topical delivery of pentazocine for the management of cancer pain.

Finasteride Topical Delivery Systems for Androgenetic Alopecia.

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover, among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes, ointments, pastes, creams, gel and lotions are still to be worthy regarding finasteride topical delivery in future.

FORMULATION, EVALUATION AND IN VITRO DISSOLUTION PERFORMANCE OF ENALAPRIL MALEATE SUSTAINED RELEASE MATRICES: EFFECT OF POLYMER COMPOSITION AND VISCOSITY GRADE.

The present study aimed at developing the sustained release matrix tablets of enalapril maleate and evaluating the effect of polymer concentration and viscosity grade on drug release. The sustained release enalapril maleate tablets were successfully formulated by direct compression method using nonionic cellulose ethers HPMC K15, HPMC K100 and HPC polymers either alone or in combination. In-vitio drug release study was carried out in phosphate buffer (pH 6.8) for a period of 24 h following USP dissolution apparatus II i.e., paddle apparatus. Model dependent approaches like zero-order, first order, Higuchi's model and Korsmeyer-Peppas model were used to assess drug release from various formulations. All the three polymers alone or in combination sustained the drug release. The drug release characteristics from HPMC and HPC polymer followed zero order release kinetics except for 45% concentration of all polymers alone or in combination where by the drug release followed Higuchi's model. In all cases, the drug release mechanism was both diffusion as well as erosion.