Release Of Moxifloxacin Research Articles

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.

Chitosan-Caffeic Acid Antibacterial Coating for PDMS Surfaces: A Sustained Moxifloxacin Release and Prolonged Coating Adhesion

Central venous catheters (CVCs) are largely used to administer chemotherapy, hemodialysis, and other treatments. Mostly made of polydimethylsiloxane (PDMS), these medical devices present an intrinsic risk of infection due to the possible formation of biofilm, thus increasing the risk of complications. Drug-releasing polymer coatings are a well-recognized strategy for combating biofilm formation. However, adhesion of the coating to the substrate over time is a major challenge. Therefore, this work aimed to design a chitosan-based coating designed to have maximum adhesion and stability to guarantee sustained drug release and antibacterial properties for at least 14 days. A coating composed of chitosan (CS) as a drug carrier, caffeic acid (CA) and copper sulphate (Cu) as crosslinkers, and moxifloxacin (Mox) as an antibiotic, was deposited through a controlled casting process onto functionalized PDMS surface. PDMS surface modification was investigated by X-ray photoelectron spectroscopy (XPS), and Fourier-transfer infrared (FTIR). Antibiotic release over time was measured in pseudo-physiological conditions (pH 7.4 and at 37 °C). Indirect cytotoxicity assays were performed on human dermal fibroblasts (HDF). The adhesion of the as-designed coating was evaluated by a specially designed pull-off test, before and after aging for 14 days in PBS. XPS and FTIR analyses confirmed the successful PDMS surface modification. The CS-CA-Cu-Mox coating resulted in being non-cytotoxic towards HDF and exhibited sustained moxifloxacin release for up to 49 days. Furthermore, the CS-CA and CS-CA-Cu coatings presented antibacterial activity for 21 days against E. coli, and for 14 days against S. aureus. Importantly, the coating maintained stable adhesion after 14 days in pseudo-physiological conditions. This study provides new insights into the adhesion behavior of polymeric coatings for medical devices, which is rarely reported in the literature.

Nanoparticles of thiolated chitosan for controlled delivery of moxifloxacin: In-vitro and in-vivo evaluation

Controlled release drug delivery system of moxifloxacin produces better therapeutic effects and maintain the plasma concentration for prolong period of time. The objective of this work was to formulate nanoparticles of thiolated chitosan (TC) having enhanced mucoadhesion and controlled release behaviour of drug. The chitosan (CS) was thiolated by conjugation with thiourea. Ionic gelation method using TC was used for the preparation of the nanoparticles. FTIR, DSC, TGA and 1H NMR were used to characterize the CS and TC. The measurement of particle size and zeta potential of the developed nanoparticles confirmed that the formulation was stable. The CS, TC and nanoparticles were evaluated for mucoadhesion and swelling. The toxicity of developed nanoparticles was evaluated by Caco-2 cell line. The release of drug from nanoparticles of non-thiolated (NT) and TC was studied using simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and phosphate buffer pH 7.4. The albino rats were used to investigate the moxifloxacin pharmacokinetics from nanoparticles of TC. The thiol group showed peak at 2122 cm−1 which was confirmed by FTIR. The thermal stability of NT and TC was confirmed by DSC and TGA. The thiolation of CS was confirmed by 1H NMR. The nanoparticle of TCN3 showed 105 nm average particle size and zeta potential of TCN1 to TCN5 was range from −18 to + 29. The TC show better mucoadhesion as compare to the CS. The drug, CS, TC and nanoparticles of TCN3 did not exhibit any effect on the viability of Caco-2 cells. In SGF, the drug release from nanoparticles was 5 to 10 %. TCN3 formulation showed 97.84% and 99.43% release of moxifloxacin in SIF and phosphate buffer pH 7.4 within 24 h. The nanoparticles of TCN3 showed 97.13% release of moxifloxacin within 8 h. The TCN3 formulation showed greater bioavailability and improved pharmacokinetic parameters of moxifloxacin as compare to the marketed formulation. Our findings proved that the thiolation of CS with thiourea is an easy and reproducible method to improve the mucoadhesion and the controlled release pattern of the drug over an extended period of time.

Cationic Polyelectrolyte Nanocapsules of Moxifloxacin for Microbial Keratitis Therapy: Development, Characterization, and Pharmacodynamic Study.

Microbial keratitis (MK) is a vision-threatening disease and the fourth leading cause of blindness worldwide. In this work, we aim to develop moxifloxacin (MXN)-loaded chitosan-based cationic mucoadhesive polyelectrolyte nanocapsules (PENs) for the effective treatment of MK. PENs were formulated by polyelectrolyte complex coacervation method and characterized for their particle size, surface charge, morphology, mucoadhesive property, in-vitro and ex-vivo release, ocular tolerance, and antimicrobial efficacy studies. The pharmacodynamic study was conducted on rabbit eye model of induced keratitis and it is compared with marketed formulation (MF). Developed PENs showed the size range from 230.7 ± 0.64 to 249.0 ± 0.49 nm and positive surface charge, spherical shape along with appropriate physico-chemical parameters. Both in-vitro and ex-vivo examination concludes that PENs having more efficiency in sustained release of MXN compared to MF. Ocular irritation studies demonstrated that no corneal damage or ocular irritation. The in-vivo study proved that the anti-bacterial efficacy of PENs was improved when compared with MF. These results suggested that PENs are a feasible choice for MK therapy because of their ability to enhance ocular retention of loaded MXN through interaction with the corneal surface of the mucous membrane.

Moxifloxacin loaded nanoparticles of disulfide bridged thiolated chitosan-eudragit RS100 for controlled drug delivery

The aim of our study was to prepare nanoparticles of disulfide bridged thiolated chitosan and eudragit RS100 using the air oxidation method for controlled drug delivery. The developed nanoparticles were characterized by FTIR, DSC, TGA, zeta sizer, zeta potential, SEM and 1H NMR. The loading, entrapment efficiency and in-vitro release of moxifloxacin from nanoparticles was determined. Toxicity was studied using Caco-2 cell line and pharmacokinetics of moxifloxacin from the developed nanoparticles was studied in albino rats. The FTIR analysis showed no chemical interaction of the drug with the thiolated polymers. The DSC and TGA showed the thermal stability of nanoparticles. The average particle size of nanoparticles was 87 nm, zeta potential of NTC3 was ± 19 and SEM showed the spherical shape of nanoparticles. The 1H NMR spectra confirmed the structure of thiolated chitosan and eudragit RS100. The loading, encapsulation efficiency and release of moxifloxacin from NTC3 were 100.3%, 89.67% and 88.49% respectively. The nanoparticles in culture medium did not affect the viability of Caco-2 cells. The NTC3 formulation showed a greater bioavailability of moxifloxacin compared to the reference formulation. The study reports a convenient and effective way to prepare a chitosan and eudragit RS100 based drug delivery system with a controlled release pattern.

The formation of quasi-regular polymeric network of cross-linked sulfobutyl ether derivative of β-cyclodextrin synthesized with moxifloxacin as a template

Sulfobutyl ether derivative of β-cyclodextrin, cross-linked in the presence of antibacterial drug moxifloxacin, forms polymeric nanoparticles (50–150 nm in diameter), with highly efficient (up to 85%) encapsulation of the drug. Cyclodextrins (CyDs) have been known for their ability to accommodate a wide range of organic molecules in their inner cavity, leading to «guest-host» inclusion complexes. Here, we show that in the case of highly cross-linked complex a substantial part of moxifloxacin molecules can be captured by the polymer's network (i.e. encapsulated in the growing 3D structure) rather than absorbed by the CyD's inner cavity. This is accompanied by dramatic changes in moxifloxacin's release kinetics profile: depending on pH, 30–100% of the drug is released from the polymer network within a week. Whereas in the case of moxifloxacin absorption on pre-synthesized CyD polymer matrix, 50% release normally occurs within hours. In vitro studies on Escherichia coli demonstrate that the moxifloxacin in highly cross-linked nanoparticle can preserve over 50% of antibacterial activity for at least 7 days, whereas the same amount of free moxifloxacin, as well as its «guest-host» complex with CyD, is inactive at this time point. The nanoparticles' ability to adhere to the bacterial cell wall may contribute to the higher activity of the smaller amount of the drug, emphasizing the potential relevance of this approach for the development of new pharmaceutical formulations.

Multi-region finite element modelling of drug release from hydrogel based ophthalmic lenses

Understanding the way in which drug is released from drug carrying hydrogel based ophthalmic lenses aids in the development of efficient ophthalmic drug delivery. Various solute–polymer interactions affect solute diffusion within hydrogels as well as hydrogel–bulk partitioning. Additionally, surface modifications or coatings may add to resistance of mass transfer across the hydrogel interface. It is necessary to consider both interfacial resistances as well as the appropriate driving force when characterizing interface flux. Such a driving force is induced by a difference in concentration which deviates from equilibrium conditions. We present a Galerkin finite element approach for solute transport in hydrogels which accounts for diffusion within the gel, storage effects due to polymer–solute interaction, as well as partitioning and mass transfer resistance effects at the interface. The approach is formulated using a rotational symmetric model to account for realistic geometry. We show that although the resulting global system is not symmetric in the case of partitioning, it is similar to a symmetric negative semidefinite system. Thus, it has non-positive real eigenvalues and is coercive, ensuring the validity of the finite element formulation as well as the numerical stability of the implicit backward Euler time integration method employed. Two models demonstrating this approach are presented and verified with release experimental data. The first is the release of moxifloxacin from intraocular lenses (IOLs) plasma grafted with different polyacrylates. The second accounts for both loading as well as the release of diclofenac from disc shaped IOL material loaded for varied time periods and temperature.

Moxifloxacin-loaded electrospun polymeric composite nanofibers-based wound dressing for enhanced antibacterial activity and healing efficacy

Nanofibers were prepared with different ratios of chitosan (CS) and polyethylene oxide (PEO) via the electrospinning technique, and tested for morphological features using scanning electron microscopy (SEM). Drug content, drug loading, release of moxifloxacin (MXF) at pH 4.7 and pH 5.5, and degree of swelling were investigated. Further characterization was accomplished via X-ray diffraction (XRD), thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR). Antibacterial activity was studied in comparison with blank nanofibers. Furthermore, wound healing was studied in Sprague-Dawley rats. A formulation consisting of CS/PEO (50/50) exhibited smooth-surfaced and beadless nanofibers having a mean diameter of 138 ± 25 nm. Drug content and drug loading in the optimized formulation, consisting of MXF, CS and PEO (0.5/2.5/2.5, w/w/w), were 99–101% and 9.1%, respectively. MXF release in 48 hours was 79.83 ± 4.2% and 94.29 ± 3.9% at pH 7.4 and pH 5.5, respectively. Moreover, degree of swelling was 133 ± 13%. The drug existed in the amorphous state and had no covalent interaction with the polymers. MXF-loaded nanofibers demonstrated greater stability, antibacterial activity and wound healing efficacy than did blank nanofibers. Accordingly, MXF-loaded CS-PEO polymeric composite nanofibers might be a potential wound dressing for effective wound healing.

Linseed hydrogel based floating drug delivery system for fluoroquinolone antibiotics: Design, in vitro drug release and in vivo real-time floating detection

Herein, we designed a novel gastroretentive drug delivery system as floating matrix tablets based on a polysaccharide material from linseeds (Linum usitatissimum L.) for fluoroquinolone antibiotics. A number of formulations were designed with a combination of linseed hydrogel (LSH) and different excipients to obtain a desired sustained release profile of moxifloxacin. The drug release study was performed basically at pH 1.2. However, the tablet may pass through the stomach to intestine due to certain reasons then it also offered sustained drug release at intestinal pH 4.5, 6.8 and 7.4, as well. Results indicated that sustained moxifloxacin release was directly proportional to the concentration of LSH and the release of drug followed non-Fickian diffusion. SEM of the tablets indicated porous nature of LSH with elongated channels which contributed to the swelling of the tablet and then facilitated the discharge of moxifloxacin from the core of the tablet. In vivo X-ray study was performed to assess disintegration and real-time floating of tablet that confirmed its presence for 6 h in the stomach. These findings indicated that LSH can be used to develop novel gastroretentive sustained release drug delivery systems with the double advantage of sustained drug release at all pH of GIT.

Moxifloxacin-loaded acrylic intraocular lenses: In vitro and in vivo performance

To assess the possibility of using acrylic intraocular lenses (IOLs) to ensure controlled and sustained release of moxifloxacin, an antibiotic commonly used for endophthalmitis prophylaxis after cataract surgery. Academic, industrial, and clinical partners from Portugal, Belgium, Iceland, and the United States. Experimental study. The physical properties of IOLs loaded with moxifloxacin by soaking were characterized. Invitro drug-release studies were performed under hydrodynamic conditions similar to those of the eye, and the activity of the released drug was tested. Invitro cytotoxicity was evaluated, and the invivo efficacy of the devices was assessed through rabbit experiments in which the effects of topical moxifloxacin drops (control) and moxifloxacin-loaded IOLs were compared. The presence of moxifloxacin in the IOLs had little effect on the evaluated physical properties and did not induce cytotoxicity. Invitro drug release experiments showed that the IOLs provided controlled release of moxifloxacin for approximately 2weeks. The drug remained active against the tested microorganisms during that period. Moxifloxacin-loaded IOLs and the control treatment induced similar invivo behavior in terms of inflammatory reactions, capsular bag opacification scores, and uveal and capsule biocompatibility. The drug concentration in the aqueous humor after 1week was similar in both groups; however, the concentration with the loaded IOLs was less variable. The moxifloxacin-loaded IOLs released the drug in a controlled manner, providing therapeutic levels.

December consultation #6

To assess the possibility of using acrylic intraocular lenses (IOLs) to ensure controlled and sustained release of moxifloxacin, an antibiotic commonly used for endophthalmitis prophylaxis after cataract surgery.Academic, industrial, and clinical partners from Portugal, Belgium, Iceland, and the United States.Experimental study.The physical properties of IOLs loaded with moxifloxacin by soaking were characterized. In vitro drug-release studies were performed under hydrodynamic conditions similar to those of the eye, and the activity of the released drug was tested. In vitro cytotoxicity was evaluated, and the in vivo efficacy of the devices was assessed through rabbit experiments in which the effects of topical moxifloxacin drops (control) and moxifloxacin-loaded IOLs were compared.The presence of moxifloxacin in the IOLs had little effect on the evaluated physical properties and did not induce cytotoxicity. In vitro drug release experiments showed that the IOLs provided controlled release of moxifloxacin for approximately 2 weeks. The drug remained active against the tested microorganisms during that period. Moxifloxacin-loaded IOLs and the control treatment induced similar in vivo behavior in terms of inflammatory reactions, capsular bag opacification scores, and uveal and capsule biocompatibility. The drug concentration in the aqueous humor after 1 week was similar in both groups; however, the concentration with the loaded IOLs was less variable.The moxifloxacin-loaded IOLs released the drug in a controlled manner, providing therapeutic levels.

Targeted delivery of antibiotics to the infected pulmonary tissues using ROS-responsive nanoparticles

BackgroundImmunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs).ResultsMXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H2O2. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs.ConclusionsOur work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.

Enhanced Surface Properties of Hydroxyapatite by Grafting Tartaric Acid for Sustained Release of Moxifloxacin

AbstractGrafting of material with organic functionalities helps to tune material's surface properties. Surface properties of a biomaterial play a significant role for sustained release of therapeutic agent. To evaluate the effect of tartaric acid concentration on HA surface properties and phase purity, a series of tartaric acid grafted HA (t‐HA) samples were prepared via in situ wet chemical synthesis. Grafting of HA with tartaric acid improved its surface properties. The surface area of 737 m2/g was gained when 0.05 mole equivalent of tartaric acid was used for HA grafting. X‐ray diffraction patterns of t‐HA samples have shown low degree of crystallinity compared to HA sample. XRD results showed the formation of calcium tartrate phase along with HA when higher concentration of tartaric acid was used for synthesis. The HA and t‐HA samples were explored for the delivery of moxifloxacin. High surface area, surface charge and low degree of crystallinity have improved electrostatic interaction between the drug and t2‐HA and help in sustained release of moxifloxacin. In vitro antibacterial activity of drug loaded samples showed activity against S. aureus. Calcium tartrate containing samples t3‐HA, t4‐HA and t5‐HA showed, however, moderate inhibition against S. aureus without drug. In vitro cell studies by using MC3T3 cell line showed that prepared HA and t‐HA samples did not exhibit any cytotoxic effect.

Release of Moxifloxacin From Corneal Collagen Shields.

To investigate the diffusion of moxifloxacin through bandage contact lenses (BCLs) versus corneal collagen shields (CSs), the relative ability of BCLs and CSs to release moxifloxacin, and the potential of release of moxifloxacin from CSs in the clinical setting. Using an in vitro model, the diffusion of 5% moxifloxacin across BCLs and CSs was compared. Next, the amount of drug release from BCLs and CSs soaked in 0.5% moxifloxacin was measured. Finally, based on a clinical model, CSs were soaked in Vigamox (commercial moxifloxacin) and the total concentration released was detected. Collagen shields remained intact after 24 hr; therefore, enzymatic digestion and mechanical grinding of the CS were performed to determine whether further drug could be released. The concentration of moxifloxacin was measured using a spectrophotometer at set time points up to 24 hr. In the diffusion assay, 35.7±10.5% diffused through the BCLs and 36.2±11.8% diffused through the CSs (P=0.77). The absorption assay demonstrated at 120 min, a total of 33.3±6.77 μg/mL was released from BCLs compared with 45.8±5.2 μg/mL from the CSs (P=0.0008). In vitro experiments to simulate clinical application of Vigamox-soaked CS found the concentration of moxifloxacin released of 127.7±7.25 μg/mL in 2 mL of phosphate-buffered saline over 24 hr. Moxifloxacin diffuses through BCLs and CSs at similar rates; however, CSs have greater capacity to absorb and release moxifloxacin compared with BCLs. Vigamox-soaked CSs released 250 μg of moxifloxacin and may be a useful method to prevent endophthalmitis.

Surface modification of an intraocular lens material by plasma-assisted grafting with 2-hydroxyethyl methacrylate (HEMA), for controlled release of moxifloxacin

Endophthalmitis, an inflammation of the eye due to perioperative infection, may occur after cataract surgery. Intraocular lenses (IOLs) loaded with an antibiotic have been proposed asan alternative to the conventional postoperative endophthalmitis prophylaxis, since the antibiotic is delivered directly to the target site. In this work, an IOL-based antibiotic releasing system was prepared from a copolymer used in the production of IOLs and a fluoroquinolone used in endophthalmitis prophylaxis (moxifloxacin, MFX). Argon plasma-assisted grafting with 2-hydroxyethyl methacrylate (HEMA) in the presence of MFX was the approach selected for surface modification, with MFX loaded both by entrapment in the grafted polyHEMA coating and by soaking. Surface and bulk properties were evaluated before and after surface modification and the MFX release profiles were obtained both in batch mode (sink conditions) and under hydrodynamic conditions, employing a purpose-built microfluidic cell, which simulated the hydrodynamic conditions around the eye lens. The effect of storage on the release profile of the best system was also assessed. The best system released MFX for ca. 15days above the minimum inhibitory concentration for Staphylococcus aureus and Staphylococcus epidermidis. The released MFX showed antimicrobial activity against these bacteria and was non-cytotoxic against corneal endothelial cells.

Controlled release of moxifloxacin from intraocular lenses modified by Ar plasma-assisted grafting with AMPS or SBMA: An in vitro study

Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention. The characterization of the modified material showed that relevant properties, like swelling capacity, wettability, refractive index and transmittance, were not affected by the surface modification. Concerning the drug release profiles, the most promising result was obtained when AMPS grafting was done in the presence of MFX. This modification led to a higher amount of drug being released for a longer period of time, which is a requirement for the prevention of endophthalmitis. The material was found to be non-cytotoxic for rabbit corneal endothelial cells. In a second step, prototype IOLs were modified with AMPS and loaded with MFX as previously and, after sterilization and storage (30days), they were tested under dynamic conditions, in a microfluidic cell with volume and renovation rate similar to the eye aqueous humour. MFX solutions collected in this assay were tested against Staphylococcus aureus and Staphylococcus epidermidis and the released antibiotic proved to be effective against both bacteria until the 12th day of release.

In Vitro Evaluation of the Drug Reservoir Function of Human Amniotic Membrane Using Moxifloxacin as a Model Drug.

To evaluate the in vitro, extended drug reservoir function of human amniotic membrane (HAM) of different thicknesses impregnated with moxifloxacin. HAM buttons (12 mm) were soaked with freshly prepared 0.5% wt/vol topical moxifloxacin at different soaking time intervals: 3 hours (group I), 6 hours (group II), 12 hours (group III), 24 hours (group IV), and 48 hours (group V). They were then transferred into 1 mL of fresh simulated tear fluid (pH-7.4) and incubated at 37°C. The release kinetics of moxifloxacin was studied by analyzing the amount of drug in simulated tear fluid collected at different time intervals from each pretreated HAM for 3 weeks. In another experiment, thin and thick HAMs were selected based on weight and soaked with moxifloxacin for 24 hours, and the release kinetics was studied for 7 weeks. All samples were stored at -80°C until analysis by high-performance liquid chromatography. No significant difference was observed between different soaking times and the release of moxifloxacin. The cumulative amount of moxifloxacin released from thick HAM was found to be statistically significant compared with thin HAM (P < 0.05). Our in vitro data showed that the sustained release of moxifloxacin from HAM was achieved up to 7 weeks. The entrapment efficiency of moxifloxacin was significantly higher in thicker HAM than in thin HAM. Moxifloxacin-impregnated HAM application can be considered in bacterial keratitis to provide sustained drug delivery through a biological bandage system for up to a period of 7 weeks.

Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing.

PurposeThe aim of this study was to evaluate and compare the release of moxifloxacin from a variety of daily disposable (DD) contact lenses (CLs) under various conditions using a novel in vitro eye model.MethodsFour commercially available DD conventional hydrogel (CH) CLs (nelfilcon A, omafilcon A, etafilcon A, and ocufilcon B) and three silicone hydrogel (SH) CLs (somofilcon A, narafilcon A, and delefilcon A) were evaluated. These lenses were incubated in moxifloxacin for 24 hours. The release of the drug was measured using a novel in vitro model in three experimental conditions: (1) phosphate buffered saline (PBS); (2) artificial tear solution (ATS) containing a variety of proteins and lipids; and (3) ATS with mechanical rubbing produced by the device.ResultsOverall, CH CLs had a higher drug release than SH CLs (P < 0.05) under all conditions. Typically, a higher drug release was observed in PBS than ATS (P < 0.05). For CH, drug release was found to be higher in ATS with rubbing than PBS or ATS (P < 0.05). For most lens types, ATS with rubbing produced higher drug release than ATS alone (P < 0.05). Generally, the release kinetics for all conditions were sustained over the 24-hour testing period, and no burst release was observed (P < 0.05).ConclusionsMoxifloxacin release from a CL into ATS is lower when compared to release into PBS. When mechanical rubbing is introduced, the amount of drugs released is increased.Translational RelevanceResults suggest that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials.

Intracellular Delivery: Redox‐Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap‐Tops Enhances Efficacy Against Pneumonic Tularemia in Mice (Small 27/2016)

Intracellular Delivery: Redox‐Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap‐Tops Enhances Efficacy Against Pneumonic Tularemia in Mice (Small 27/2016)

Redox-Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap-Tops Enhances Efficacy Against Pneumonic Tularemia in Mice.

Effective and rapid treatment of tularemia is needed to reduce morbidity and mortality of this potentially fatal infectious disease. The etiologic agent, Francisella tularensis, is a facultative intracellular bacterial pathogen which infects and multiplies to high numbers in macrophages. Nanotherapeutics are particularly promising for treatment of infectious diseases caused by intracellular pathogens, whose primary host cells are macrophages, because nanoparticles preferentially target and are avidly internalized by macrophages. A mesoporous silica nanoparticle (MSN) has been developed functionalized with disulfide snap-tops that has high drug loading and selectively releases drug intracellularly in response to the redox potential. These nanoparticles, when loaded with Hoechst fluorescent dye, release their cargo exclusively intracellularly and stain the nuclei of macrophages. The MSNs loaded with moxifloxacin kill F. tularensis in macrophages in a dose-dependent fashion. In a mouse model of lethal pneumonic tularemia, MSNs loaded with moxifloxacin prevent weight loss, illness, and death, markedly reduce the burden of F. tularensis in the lung, liver, and spleen, and are significantly more efficacious than an equivalent amount of free drug. An important proof-of-principle for the potential therapeutic use of a novel nanoparticle drug delivery platform for the treatment of infectious diseases is provided.