A Computational Pipeline to Predict Cardiotoxicity: From the Atom to the Rhythm.

RATIONALE: Drug-induced proarrhythmia is so tightly associated with prolongation of the QT interval that QT prolongation is an accepted surrogate marker for arrhythmia. But QT interval is too sensitive a marker and not selective, resulting in many useful drugs eliminated in drug discovery. OBJECTIVE: To predict the impact of a drug from the drug chemistry on the cardiac rhythm. METHODS AND RESULTS: In a new linkage, we connected atomistic scale information to protein, cell, and tissue scales by predicting drug-binding affinities and rates from simulation of ion channel and drug structure interactions and then used these values to model drug effects on the hERG channel. Model components were integrated into predictive models at the cell and tissue scales to expose fundamental arrhythmia vulnerability mechanisms and complex interactions underlying emergent behaviors. Human clinical data were used for model framework validation and showed excellent agreement, demonstrating feasibility of a new approach for cardiotoxicity prediction. CONCLUSIONS: We present a multiscale model framework to predict electrotoxicity in the heart from the atom to the rhythm. Novel mechanistic insights emerged at all scales of the system, from the specific nature of proarrhythmic drug interaction with the hERG channel, to the fundamental cellular and tissue-level arrhythmia mechanisms. Applications of machine learning indicate necessary and sufficient parameters that predict arrhythmia vulnerability. We expect that the model framework may be expanded to make an impact in drug discovery, drug safety screening for a variety of compounds and targets, and in a variety of regulatory processes.

A rapid RP-HPLC stability-indicating method development and validation of moxifloxacin hydrochloride-related substances in finished dosage forms.

A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the identification and quantification of moxifloxacin hydrochloride-related substances in finished dosage forms. Chromatographic separation was achieved on an Agilent C18 column (150 × 4.6 mm, 5 µm) with the mobile phase (0.01 M potassium dihydrogen orthophosphate as buffer and methanol in the ratio of 70:30) eluted in isocratic mode. The HPLC flow rate was 1.0 mL min-1 , and peaks were monitored at 230 nm using a photodiode array (PDA) detector. The column temperature was kept constant at 30°C, and the injection volume was 10 µL. The run time of the method was 16 min. The method was validated as per the International Conference on Harmonization (ICH) guidelines. Linearity was recorded at various concentrations ranging from 0.25 to 1.5 µg mL-1 for all the moxifloxacin impurities. Linearity, regression value, recovery, %relative standard deviation (RSD) of method precision values were found within the acceptance limits. The method for related substances (RS) in moxifloxacin was found to be specific, linear, accurate, precise, rugged, and robust. The validated method was suitable for the quantification of the RSs in moxifloxacin drug products. The method was applied in quality control lab for the analysis of moxifloxacin impurities in stability analysis.

Synthesis and Characterization of Mesoporous Mg- and Sr-Doped Nanoparticles for Moxifloxacin Drug Delivery in Promising Tissue Engineering Applications.

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol-gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.

Stimuli Responsive In Situ Gelling Systems Loaded with PLGA Nanoparticles of Moxifloxacin Hydrochloride for Effective Treatment of Periodontitis.

The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1 week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1 week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3 weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment.

Development of Chitosan-Based Hydrogel Containing Antibiofilm Agents for the Treatment of Staphylococcus aureus-Infected Burn Wound in Mice.

Methicillin-resistant Staphylococcus aureus (MRSA) is considered a common colonizer of burn wound and accounts for high morbidity and mortality all across the globe. Systemic antibiotic therapy which is generally prescribed for these patients has a number of limitations. These include high drug dose, toxicity, and chances of development of drug resistance. However, local delivery of drug not only addresses these limitations but also provides better efficacy at the site of infection. In the present study, hydrogel preparations were developed for the topical delivery of moxifloxacin for the treatment of S. aureus-infected burn wound. Moxifloxacin was characterized by UV, FTIR, DSC, hot-stage microscopy, NMR, and HPLC and loaded into conventional and Boswellia-containing novel gels. Gels were characterized by visual examination, pH, UV spectroscopy, and release assays. In vivo studies showed that both gels were effective in eradicating the bacteria completely from the wound site when treatment was started during the early stage of infection. On the contrary, delayed treatment of planktonic and biofilm cells with novel gel showed better efficacy as compared with conventional gel in S. aureus-infected burn wound. Histopathological analysis also showed better skin healing efficacy of novel gel than conventional gel. Our results show that moxifloxacin can be efficiently used topically in the management of burn wound infections along with other antibacterial agents. Since biofilm-mediated infections are on the rise especially in chronic bacterial disease, therefore, a preparation containing antibiofilm agent-like Boswellia as one of the excipients would be more meaningful.

Design, synthesis and antibacterial activity evaluation of moxifloxacin-amide-1,2,3-triazole-isatin hybrids.

In this work, a series of novel moxifloxacin-amide-1,2,3-triazole-isatin hybrids 7a-l were designed and synthesized. The in vitro antibacterial activity against a panel of clinically important Gram-positive and Gram-negative bacteria including drug-resistant pathogens was also evaluated. All hybrids showed considerable activity against the tested pathogens with MIC values of ≤0.03 to 128 µg/mL, and some of them such as hybrids 7e, 7g and 7j were comparable to or better than the parent moxifloxacin (MIC: ≤0.03-8 µg/mL). Moreover, hybrids 7e, 7g and 7j also demonstrated low cytotoxicity towards CHO cells. However, the in vivo pharmacokinetic profiles of these three hybrids were generally far inferior to the parent moxifloxacin. The structure-activity relationship and structure-cytotoxicity relationship were also studied and discussed which may help with the identification of new chemical entities as potent antibacterial agents.

Design, synthesis and molecular modeling studies on novel moxifloxacin derivatives as potential antibacterial and antituberculosis agents.

Twenty-one novel alkyl/acyl/sulfonyl substituted fluoroquinolone derivatives were designed, synthesized and evaluated for their anti-tuberculosis and antibacterial activity. The targeted compounds were synthesized by the introduction of alkyl, acyl or sulfonyl moieties to the basic secondary amine moiety of moxifloxacin. Structures of the compounds were enlightened by FT-IR, 1H NMR, 13C NMR and HRMS data besides elemental analysis. Compounds were initially tested in vitro for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay. Minimal inhibitory concentration (MIC) values of all compounds were found between > 25.00-0.39 µg/mL while compounds 1, 2 and 13 revealed an outstanding activity against M. tuberculosis H37Rv with MIC values of 0.39 µg/mL. Activities of compounds 1-21 against to a number of Gram-positive and Gram-negative bacteria and fast growing mycobacterium strain were also investigated by agar well diffusion and microdilution methods. According to antimicrobial activity results, compound 13 was found the most potent derivative with a IC50 value of <1.23 µg/mL against Staphylococcus aureus and clinical strain of methicillin-resistant clinical strain of S. aureus.

Biological Investigations and Spectroscopic Studies of New Moxifloxacin/Glycine-Metal Complexes.

Two novel ligand-metal complexes were prepared through the reaction of Zn(II) and Sn(II) with moxifloxacin (MOX) in the presence of glycine (Gly) to investigate their biological activities. IR, UV/VIS and 1 H-NMR analysis have been carried out for insuring the chelation process. Results suggested that MOX and Gly react with the metal ions through the carbonyl oxygen atom and the oxygen atom of the carboxylic group of MOX and Gly. The antimicrobial activity was carried out against some common bacterial and fungal pathogens and the radical scavenging activity (RSA%) was evaluated using DPPH and ABTS methods. Phytotoxic effect of the prepared complexes was evaluated in vitro against Raphanus raphanistrum and Lepidium sativum. Hemolytic activity was tested against cell membrane of erythrocytes. Results showed that the two prepared complexes exhibited high antimicrobial activity against all tested phytopathogens and no significant phytotoxic effect has been observed. Only MOX-Zn(II) complex showed moderate hemolysis at 100 % concentration.

1H-1,2,3-Triazole tethered isatin-moxifloxacin: Design, synthesis and in vitro anti-mycobacterial evaluation.

A series of novel 1H-1,2,3-triazole tethered isatin-moxifloxacin (MXF) hybrids 5a-l with greater lipophilicity compared with the parent MXF were designed, synthesized and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H37 Rv and multidrug-resistant MTB (MDR-MTB) as well as their cytotoxicity on the VERO cell line. All the synthesized hybrids (MIC: 0.025-0.78 µg/ml) showed considerable activities against MTB H37 Rv and MDR-MTB, and the most active conjugate 5c (MIC: 0.025 and 0.06 µg/ml) was 2 to >2048 times more potent in vitro than the three references MXF (MIC: 0.10 and 0.12 µg/ml), rifampicin (MIC: 0.39 and 32 µg/ml) and isoniazid (MIC: 0.05 and >128 µg/ml) against the two tested strains. All hybrids (CC50 : 4-64 µg/ml) were much more cytotoxic than the parent MXF (CC50: 128 µg/ml), but the most active hybrid 5c (CC50 : 32 µg/ml) also displayed acceptable cytotoxicity, warranting further investigation.

Carrier-free combination dry powder inhaler formulation of ethionamide and moxifloxacin for treating drug-resistant tuberculosis.

This study aimed to develop a combination dry powder formulation of ethionamide and moxifloxacin HCl as this combination is synergistic against drug-resistant Mycobacterium tuberculosis (Mtb). L-leucine (20% w/w) was added in the formulations to maximize the process yield. Moxifloxacin HCl and/or ethionamide powders with/without L-leucine were produced using a Buchi Mini Spray-dryer. A next generation impactor was used to determine the in vitro aerosolization efficiency. The powders were also characterized for other physicochemical properties and cytotoxicity. All the spray-dried powders were within the aerodynamic size range of <5.0 µm except ethionamide-only powder (6.0 µm). The combination powders with L-leucine aerosolized better (% fine particle fraction (FPF): 61.3 and 61.1 for ethionamide and moxifloxacin, respectively) than ethionamide-only (%FPF: 9.0) and moxifloxacin-only (%FPF: 30.8) powders. The combination powder particles were collapsed with wrinkled surfaces whereas moxifloxacin-only powders were spherical and smooth and ethionamide-only powders were angular-shaped flakes. The combination powders had low water content (<2.0%). All the powders were physically stable at 15% RH and 25 ± 2 °C during 1-month storage and tolerated by bronchial epithelial cell-lines up to 100 µg/ml. The improved aerosolization of the combination formulation may be helpful for the effective treatment of drug-resistant tuberculosis. Further studies are required to understand the mechanisms for improved aerosolization and test the synergistic activity of the combination powder.

Synthesis, characterization, antimicrobial and enzyme inhibitory studies of moxifloxacin with aromatic carboxylic acids.

A series of carboxamide derivatives of moxifloxacin has been synthesized. The synthesized derivatives has been characterization by using spectroscopic techniques such as UV-Vis, IR, H1NMR and Mass spectra, which suggested that incoming group has occupied azabicylo groups of selected moxifloxacin at 7th position. Antimicrobial screening has been systematically carried out against various gram-positive, Gram-negatives and fungi in comparison with parent drug. Enzymatic assay were also performed. The results obtained were statistically analyzed by one way ANOVA. The antimicrobial results reveals that the synthesized derivative of moxifloxacin possess good activities against B. subtilis, F. solani, T. rubrum and P. aeruginosa concluding that derivatives are more potent antimicrobial agents as compared to parent drug. While compound B1 solely possess mild enzymatic activity against urease whereas, no other compounds is active against both urease and carbonic anhydrase.

Moxifloxacin-Ester derivatives: Synthesis, characterization and pharmacological evaluation.

It is known that resistance of bacteria is one of the major issues in drug treatment. To cope this issue, it is required to synthesize new analogues which contest against mutated bacteria. This research study included synthesis of several derivatives of moxifloxacin by adding different phenol and alkyl halide at third position of carboxylic group with esterification reaction and the structures of synthesized derivatives were characterized by spectroscopic techniques i.e. 1H NMR, FT-IR and mass-spectrometry. In continuation, antimicrobial activities of the analogues were also evaluated against number of Gram-positive, Gram-negative bacteria and fungi. The experimental results of novel derivatives exhibit significant antibacterial and antifungal profile in which so many synthesized derivatives influenced a similar and enhanced activity against selected microbes that were S. typhi, P. mirabilis, P. aeruginosa, S. flexneri, B. subtilis as compared to the moxifloxacin. Moreover, few innovative derivatives were also produced better anti-fungal activity against F. solani and T. rubrum. Furthermore, the enzymatic activity of all analogues has been analyzed against urease and carbonic anhydrase and concluded that C2 was selected inhibitor of urease enzyme.

Triple combination dry powder formulation of pretomanid, moxifloxacin, and pyrazinamide for treatment of multidrug-resistant tuberculosis.

Both latent and multidrug-resistant tuberculosis (TB) have been causing significant concern worldwide. A novel drug, pretomanid (PA-824), has shown a potent bactericidal effect against both active and latent forms of Mycobacterium tuberculosis (MTb) and a synergistic effect when combined with pyrazinamide and moxifloxacin. This study aimed to develop triple combination spray dried inhalable formulations composed of antitubercular drugs, pretomanid, moxifloxacin, and pyrazinamide (1:2:8 w/w/w), alone (PaMP) and in combination with an aerosolization enhancer, L-leucine (20 % w/w, PaMPL). The formulation PaMPL consisted of hollow, spherical, dimpled particles (<5 µm) and showed good aerosolization behaviour with a fine particle fraction of 70 %. Solid-state characterization of formulations with and without L-leucine confirmed the amorphous nature of moxifloxacin and pretomanid and the crystalline nature of pyrazinamide with polymorphic transformation after the spray drying process. Further, the X-ray photoelectron spectroscopic analysis revealed the predominant surface composition of L-leucine on PaMPL dry powder particles. The dose-response cytotoxicity results showed pyrazinamide and moxifloxacin were non-toxic in both A549 and Calu-3 cell lines up to 150 µg/mL. However, the cell viability gradually decreased to 50 % when the pretomanid concentration increased to 150 µg/mL. The in vitro efficacy studies demonstrated that the triple combination formulation had more prominent antibacterial activity with a minimum inhibitory concentration (MIC) of 1 µg/mL against the MTb H37Rv strain as compared to individual drugs. In conclusion, the triple combination of pretomanid, moxifloxacin, and pyrazinamide as an inhalable dry powder formulation will potentially improve treatment efficacy with fewer systemic side effects in patients suffering from latent and multidrug-resistant TB.

A Periosteum-Bioinspired Electrospun Janus Membrane with Antibacterial and Osteogenic Dual Function.

For a guided bone regeneration membrane, it is critical to possess osteogenic capability while inhibiting infection caused by bacteria. Inspired by the bilayer structure of the native periosteum, an electrospun Janus membrane with osteogenic and antibacterial dual-function is fabricated for guided bone regeneration. Hydrophilic moxifloxacin (MXF) and hydrophobic icariin (ICA) are loaded in the nanofibers made of a mixture of polycaprolactone and gelatin at the top and bottom layers, respectively, leading to the opposing hydrophilic/hydrophobic properties of the bilayer Janus membranes. The as-obtained Janus membrane exhibits excellent physical properties (tensile strength > 6.0 MPa) and robust biocompatibility, indicating the immense potential as a suitable replacement for the native periosteum. The membrane has a superior surface morphology and outstanding degradation performance in vitro. Besides, the rapid release of MXF and the slow release of ICA can meet the different needs of drug release rates. Only ≈30% ICA is released from the as-obtained Janus membrane after 21 d while almost 80% MXF is released. Mimicking the bilayer structure of the native periosteum, the electrospun Janus membrane containing ICA and MXF exhibits excellent comprehensive properties, which provides a promising strategy for preparing multifunctional scaffolds for tissue engineering.

Nanocrystalline cellulose as a reinforcing agent for poly (vinyl alcohol)/ gellan-gum-based composite film for moxifloxacin ocular delivery.

Nanocrystalline cellulose (NCC) is a star material in drug delivery applications due to its good biocompatibility, large specific surface area, high tensile strength (TS), and high hydrophilicity. Poly(Vinyl Alcohol)/Gellan-gum-based innovative composite film has been prepared using nanocrystalline cellulose (PVA/GG/NCC) as a strengthening agent for ocular delivery of moxifloxacin (MOX) via solvent casting method. Impedance analysis was studied using the capacitive sensing technique for examining new capacitance nature of the nanocomposite MOX film. Antimicrobial properties of films were evaluated using Pseudomonas aeruginosa and Staphylococcus aureus as gram-negative and gram-positive bacteria respectively by disc diffusion technique. XRD revealed the characteristic peak of NCC and the amorphous form of the drug. Sustained in vitro release and enhanced corneal permeation of drug were noticed in the presence of NCC. Polymer matrix enhanced the mechanical properties (tensile strength 22.05 to 28.41 MPa) and impedance behavior (resistance 59.23 to 213.23 Ω) in the film due to the presence of NCC rather than its absence (16.78 MPa and 39.03 Ω respectively). Occurrence of NCC brought about good antimicrobial behavior (both gram-positive and gram-negative) of the film. NCC incorporated poly(vinyl alcohol)/gellan-gum-based composite film exhibited increased mechanical properties and impedance behavior for improved ocular delivery of moxifloxacin.

Moxifloxacin-loaded nanoparticles of thiolated xyloglucan for ocular drug delivery: Permeation, mucoadhesion and pharmacokinetic evaluation.

The current study goal was to improve mucoadhesive potential and ocular pharmacokinetics of nanoparticles of thiolated xyloglucan (TXGN) containing moxifloxacin (MXF). Thiolation of xyloglucan (XGN) was achieved with esterification with 3-mercaptopropionic acid. TXGN was characterized by NMR and FTIR analysis. The nanoparticles of TXGN were prepared using ionic-gelation method and evaluate the antibacterial properties. TXGN and nanoparticles were determined to possess 0.06 and 0.08 mmol of thiol groups/mg of polymer by Ellman's method. The ex-vivo bioadhesion time of TXGN and nanoparticles was higher than XGN in a comparative assessment of their mucoadhesive properties. The creation of a disulfide link between mucus and TXGN is responsible for the enhanced mucoadhesive properties of TXGN (1-fold) and nanoparticles (2-fold) over XGN. Improved MXF penetration in nanoparticulate formulation (80 %) based on TXGN was demonstrated in an ex-vivo permeation research utilizing rabbit cornea. Dissolution study showed 95 % release of MXF from nanoparticles. SEM images of nanoparticles showed spherical shape and cell viability assay showed nontoxic behavior when tested on RPE cell line. Antibacterial analysis revealed a zone of inhibition of 31.5 ± 0.5 mm for MXF, while NXM3 exhibited an expanded zone of 35.5 ± 0.4 mm (p < 0.001). In conclusion, thiolation of XGN improves its bioadhesion, permeation, ocular-retention and pharmacokinetics of MXF.

Drug-impregnated contact lenses via supercritical carbon dioxide: A viable solution for the treatment of bacterial and fungal keratitis.

Keratitis is a corneal infection caused by various bacteria and fungi. Eye drop treatment of keratitis involves significant challenges due to difficulties in administration, inefficiencies in therapeutic dosage, and frequency of drug applications. All these are troublesome and result in unsuccessful treatment, high cost, time loss, development of drug resistance by microorganisms, and a massive burden on human health and the healthcare system. Most of the antibacterial and antifungal medications are non-water-soluble and/or include toxic drug formulations. Here, the aim was to develop drug-loaded contact lenses with therapeutic dosage formulations and extended drug release capability as an alternative to eye drops, by employing supercritical carbon dioxide (ScCO2) as a drug impregnation solvent to overcome inefficient ophthalmic drug use. ScCO2, known as a green solvent, has very low viscosity which provides high mass transfer power and could enhance drug penetration into contact lenses much better with respect to drug loading using other solvents. Here, moxifloxacin (MOX) antibiotic and amphotericin B (AMB) antifungal medicines were separately loaded into commercially available silicone hydrogel contact lenses through 1) drug adsorption from the aqueous solutions and 2) impregnation techniques via ScCO2 and their efficacies were compared. Drug impregnation parameters, i.e., 8-25 MPa pressure, 310-320 K temperature, 2-16-hour impregnation times, and the presence of ethanol as polar co-solvent were investigated for the optimization of the ScCO2 drug impregnation process. The highest drug loading and long-term release kinetic from the contact lenses were obtained at 25 MPa and 313 K with 2.5 h impregnation time by using 1 % ethanol (by volume). Furthermore, antibacterial/antifungal activities of the MOX- and AMB-impregnated contact lenses were effective against in vitro Pseudomonas aeruginosa (ATCC 10145) bacteria and Fusarium solani (ATCC 36031) fungus for up to one week. Consequently, the ScCO2 method can be effectively used to impregnate commercial contact lenses with drugs, and these can then be safely used for the treatment of keratitis. This offers a sustainable delivery system at effective dosage formulations with complete bacterial/fungal inhibition and termination, making it viable for real animal/human applications.

Dual Drug-Loaded Coaxial Nanofiber Dressings for the Treatment of Diabetic Foot Ulcer.

Introduction: Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization. Rationale: To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds. Results: The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 µg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 µg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 µg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 µg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups. Conclusion: These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.

Cationic Chitosan/Pectin Polyelectrolyte Nanocapsules of Moxifloxacin as Novel Topical Management System for Bacterial Keratitis.

PURPOSE: Moxifloxacin (MOX) is a fourth-generation fluoroquinolone and a broad spectrum antibiotic used in the management of bacterial keratitis (BK). This investigation aimed to formulate MOX-loaded chitosan/pectin cationic polyelectrolyte nanocapsules (CPNCs) for the effective topical treatment of BK. METHODS: Physicochemical properties like nanocapsule size, charge, drug entrapment efficiency (EE), viscosity, pH, and in-vitro release profile of CPNCs were evaluated. The in-vitro antibacterial activity of CPNCs and marketed formulations (MFs) was studied against Staphylococcus aureus. Ex-vivo corneal permeation studies of CPNCs were evaluated with the help of a modified diffusion apparatus, which was used with goat cornea. The pharmacodynamic study was performed with optimized CPNCs on a BK-induced rabbit eye model and compared with MF. RESULTS: The optimized nanocapsules appeared as positive charge (+19.91 ± 0.66) with a nano size (242.0 ± 0.30 nm) as calculated by the dynamic light scattering method. The in-vitro release profile of CPNCs exhibited sustained release properties. The ex-vivo permeation pattern also supported the improved drug permeation through the cornea from CPNCs as compared with MF. Draize irritation studies confirmed that the prepared formulation is compatible with the corneal tissue. The in-vivo study concluded that the antibacterial activity of CPNCs was improved when evaluated with MF. CONCLUSION: The obtained results showed that CPNCs were the better choice for the management of BK therapy due to its capability to improve the corneal adhesion of CPNCs through direct interaction with the mucous membrane of the corneal tissue.

Moxifloxacin Hydrochloride-Loaded Eudragit® RL 100 and Kollidon® SR Based Nanoparticles: Formulation, In vitro Characterization and Cytotoxicity.

BACKGROUND: Considering the low ocular bioavailability of conventional formulations used for ocular bacterial infection treatment, there is a need to design efficient novel drug delivery systems that may enhance precorneal retention time and corneal permeability. AIM AND OBJECTIVE: The current research focuses on developing nanosized and non-toxic Eudragit® RL 100 and Kollidon® SR nanoparticles loaded with moxifloxacin hydrochloride (MOX) for its prolonged release to be promising for effective ocular delivery. METHODS: In this study, MOX incorporation was carried out by spray drying method aiming ocular delivery. In vitro characteristics were evaluated in detail with different methods. RESULTS: MOX was successfully incorporated into Eudragit® RL 100 and Kollidon® SR polymeric nanoparticles by a spray-drying process. Particle size, zeta potential, entrapment efficiency, particle morphology, thermal, FTIR, NMR analyses and MOX quantification using HPLC method were carried out to evaluate the nanoparticles prepared. MOX loaded nanoparticles demonstrated nanosized and spherical shape while in vitro release studies demonstrated modified-release pattern, which followed the Korsmeyer-Peppas kinetic model. Following the successful incorporation of MOX into the nanoparticles, the formulation (MOX: Eudragit® RL 100, 1:5) (ERL-MOX 2) was selected for further studies because of its better characteristics like cationic zeta potential, smaller particle size, narrow size distribution and more uniform prolonged release pattern. Moreover, ERLMOX 2 formulation remained stable for 3 months and demonstrated higher cell viability values for MOX. CONCLUSION: In vitro characterization analyses showed that non-toxic, nano-sized and cationic ERL-MOX 2 formulation has the potential of enhancing ocular bioavailability.