Spray-dried pH-sensitive chitosan microparticles loaded with Mycobacterium bovis BCG intended for supporting treatment of Helicobacter pylori infection.

Gram-negative spiral-shaped Helicobacter pylori (Hp) bacteria induce the development of different gastric disorders. The growing resistance of Hp to antibiotics prompts to search for new therapeutic formulations. A promising candidate is Mycobacterium bovis BCG (BCG) with immunomodulatory properties. Biodegradable mucoadhesive chitosan is a good carrier for delivering BCG mycobacteria to the gastric mucosal environment. This study aimed to show whether BCG bacilli are able to increase the phagocytic activity of Cavia porcellus-guinea pig macrophages derived from the bone marrow towards fluorescently labeled Escherichia coli. Furthermore, to encapsulate live BCG bacilli, in spray-dried chitosan microparticles (CHI-MPs), and assess the pH-dependent release of mycobacteria in pH conditions mimicking gastric (acidic) or gut (alkaline) milieu. Microparticles (MPs) were made of chitosan and coated with Pluronic F-127-(Plur) or N-Acetyl-D-Glucosamine-(GlcNAc) to increase the MPs resistance to low pH or to increase anti-Hp effect, respectively. Spray-drying method was used for microencapsulation of live BCG. The biosafety of tested CHI-MPs has been confirmed using cell models in vitro and the model of guinea pig in vivo. The CHI-MPs loaded with BCG released live mycobacteria at pH 3.0 (CHI-GlcNAc-MPs) or pH 8.0. (CHI-Plur-MPs). The CHI-MPs loaded with live BCG can be used for per os inoculation of Cavia porcellus to check the effectiveness of delivered mycobacteria in increasing anti-H. pylori host response.

Polymer based dual drug delivery system for targeted treatment of fluoroquinolone resistant Staphylococcus aureus mediated infections.

The present study attempts to treat S. aureus-induced soft skin infections using a combinatorial therapy with an antibiotic, Ciprofloxacin (CIP), and an efflux pump inhibitor 5-Nitro-2-(3-phenylpropoxy) pyridine (5-NPPP) through a smart hydrogel delivery system. The study aims to reduce the increasing rates of infections and antimicrobial resistance; therefore, an efflux pump inhibitor molecule is synthesized and delivered along with an antibiotic to re-sensitize the pathogen towards antibiotics and treat the infections. CIP-loaded polyvinyl alcohol (PVA) hydrogels at varying concentrations were fabricated and optimized by a chemical cross-linking process, which exhibited sustained drug release for 5 days. The compound 5-NPPP loaded hydrogels provided linear drug release for 2 days, necessitating the need for the development of polymeric nanoparticles to alter the release drug pattern. 5-NPPP loaded Eudragit RSPO nanoparticles were prepared by modified nanoprecipitation-solvent evaporation method, which showed optimum average particle size of 230-280 nm with > 90% drug entrapment efficiency. The 5-NPPP polymeric nanoparticles loaded PVA hydrogels were fabricated to provide a predetermined sustained release of the compound to provide a synergistic effect. The selected 7% PVA hydrogels loaded with the dual drugs were evaluated using Balb/c mice models induced with S. aureus soft skin infections. The results of in vivo studies were evidence that the dual drugs loaded hydrogels were non-toxic and reduced the bacterial load causing re-sensitization towards antibiotics, which could initiate re-epithelization. The research concluded that the PVA hydrogels loaded with CIP and 5-NPPP nanoparticles could be an ideal and promising drug delivery system for treating S. aureus-induced skin infections.

Spray-dried tenofovir alafenamide-chitosan nanoparticles loaded oleogels as a long-acting injectable depot system of anti-HIV drug.

The development of suitable drug delivery systems for prolonged action against HIV receives great attention in recent research. Herein, a long-acting injectable (LAI) of Tenofovir alafenamide-chitosan polymeric nanoparticles loaded oleogels developed with sesame oil and ethyl cellulose for prolonged release of the drug is reported for the first time. The research resulted with unique long-acting parenteral formulation for chronic anti-retroviral therapy, based on our experimental in-vitro and ex-vivo studies. The chitosan nanoparticles with 49 % drug content were produced through the spray-drying technique and characterized for their size (106-540 nm) and the other physico-chemical features through SEM, FT-IR, XRD, TGA, and DSC. The ethyl cellulose and sesame oil oleogels were developed through a heat-cool process by incorporating the drug-loaded chitosan nanoparticles. The oleogels exhibited extended release (56 %) of the drug for 16 days, which could be prolonged further to achieve the maximum drug release. Also, the ex-vivo permeation studies of the nanoparticles loaded oleogels demonstrated about 10-fold decrease in the flux and the permeation of the drug due to prolonged release of the drug across dual barriers of chitosan nanoparticles and ethyl cellulose gel matrix. The result provided proof-of-evidence that the developed Tenofovir alafenamide-chitosan polymeric nanoparticles loaded with ethyl cellulose oleogels could be potentially used as the long-acting injectable system for the treatment of patients infected with HIV/AIDS.

Lamotrigine Nanoparticle Laden Polymer Composite Oral Dissolving Films for Improving Therapeutic Potential of the Hydrophobic Antiepileptic Molecule.

Lamotrigine is used for neurological disorders and antiepileptic therapy at frequent dosing due to its poor solubility. The present work aims to study the influence of combining the Lamotrigine nanoparticles and polymer composite oral dissolving film to improve the solubility and dissolution kinetics of the drug. The Lamotrigine-Eudragit E100 nanoparticles were synthesized through solvent evaporation followed by precipitation process, which were laden in oral dissolving films through solvent casting technique. The optimized nanoparticles were assessed for particle size, colloidal stability, drug entrapment efficiency, in vitro release profile, physicochemical characteristics, and cytotoxicity. The optimized polymeric nanoparticles of Lamotrigine: Eudragit E100 (1:0.5) exhibited monodispersed particles with 103 nm average size, +7.96 mV zeta potential, and 82.96% ± 1.2% entrapment efficiency. The composite oral matrix films blended with polyvinyl alcohol and polyvinyl pyrrolidone (0.5:0.5 ratio) incorporated with the polymeric nanoparticles demonstrated >64% drug release within 2 h. The nanoparticles and its composite films exhibited 9- and 11-fold higher drug release than pure drug, respectively. The analytical characterization studies proved the formation of nanoparticles with mild drug-polymer interactions and optimum stability, which resulted in enhanced solubility and dissolution of drug. The nanoparticles displayed lesser cytotoxicity to the normal (Vero) cells at concentration of 10-50 µg/mL compared to pure drug. The optimized polymeric nanoparticle loaded oral films could be suitable for in vivo administration of Lamotrigine at low doses to improve bioavailability and therapeutic efficiency with reduced side effects.

Silver Nanomaterials for Wound Dressing Applications.

Silver nanoparticles (AgNPs) have recently become very attractive for the scientific community due to their broad spectrum of applications in the biomedical field. The main advantages of AgNPs include a simple method of synthesis, a simple way to change their morphology and high surface area to volume ratio. Much research has been carried out over the years to evaluate their possible effectivity against microbial organisms. The most important factors which influence the effectivity of AgNPs against microorganisms are the method of their preparation and the type of application. When incorporated into fabric wound dressings and other textiles, AgNPs have shown significant antibacterial activity against both Gram-positive and Gram-negative bacteria and inhibited biofilm formation. In this review, the different routes of synthesizing AgNPs with controlled size and geometry including chemical, green, irradiation and thermal synthesis, as well as the different types of application of AgNPs for wound dressings such as membrane immobilization, topical application, preparation of nanofibers and hydrogels, and the mechanism behind their antimicrobial activity, have been discussed elaborately.

A polymer-based anti-quorum catheter coating to challenge MDR Staphylococcus aureus: in vivo and in vitro approaches.

BACKGROUND: MDR Staphylococcus aureus is a major aetiological agent of catheter-associated infections. A quorum sensing targeted drug development approach proves to be an effective alternative strategy to combat such infections. METHODS: Intravenous catheters were coated with polymethacrylate copolymers loaded with the antivirulent compound 2-[(methylamino)methyl]phenol (2MAMP). The in vitro drug release profile and kinetics were established. The anti-biofilm effect of the coated catheters was tested against clinical isolates of MDR S. aureus. The in vivo studies were carried out using adult male Wistar rats by implanting coated catheters in subcutaneous pockets. Histopathological analysis was done to understand the immunological reactions induced by 2MAMP. RESULTS: A uniform catheter coating of thickness 0.1 mm was achieved with linear sustained release of 2MAMP for 6 h. The coating formulation was cytocompatible. The in vitro and in vivo anti-adherence studies showed reduced bacterial accumulation in coated catheters after 48 h. The histopathological results confirmed that the coated catheter did not bring about any adverse inflammatory response. CONCLUSIONS: The developed anti-quorum-coated catheter that is non-toxic and biocompatible has the potential to be used in other medical devices, thereby preventing catheter-associated infections.