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An ion-paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection.

ABSTRACT: There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance. Here, we describe an ion-pairing approach used to create an insoluble moxifloxacin-pamoate (MOX-PAM) complex for formulation into mucus-penetrating nanosuspension eye drops (MOX-PAM NS). The MOX-PAM NS provided a significant increase in ocular drug absorption, as measured by the area under the curve in cornea tissue and aqueous humor, compared to Vigamox in healthy rats. Prophylactic and treatment efficacy were evaluated in a rat model of ocular Staphylococcus aureus infection. A single drop of MOX-PAM NS was more effective than Vigamox, and completely prevented infection. Once a day dosing with MOX-PAM NS was similar, if not more effective, than three times a day dosing with Vigamox for treating S. aureus infection. The MOX-PAM NS provided increased intraocular antibiotic absorption and improved prevention and treatment of ocular keratitis, and the formulation approach is highly translational and clinically relevant.

SUBMITTER: Josyula A

PROVIDER: S-EPMC8459599 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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An ion-paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection.

Josyula Aditya A Omiadze Revaz R Parikh Kunal K Kanvinde Pranjali P Appell Matthew B MB Patel Pratikkumar P Saeed Hiwa H Sutar Yogesh Y Anders Nicole N He Ping P McDonnell Peter J PJ Hanes Justin J Date Abhijit A AA Ensign Laura M LM

Bioengineering & translational medicine 20210622 3

There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance. Here, we describe an ion-pairing approach used to create an insoluble mox ...[more]

PMID: 34589607

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Project description:BACKGROUND:Zotepine (ZTP), an antipsychotic drug is well tolerated and particularly effective for treating negative symptoms of psychosis. But is limited by low oral bioavailability caused by substantial first pass metabolism and thereby less amount of drug reaches the brain due to blood brain barrier (BBB). OBJECTIVES:Since ZTP displays dose dependent side effects, purpose of the contemporary study is to develop zotepine loaded nanosuspension (ZTP-NS) for increased brain targeting in rats at lower doses. METHODS:ZTP-NS is prepared by two techniques viz., sonoprecipitation (SP) and combination technique (high pressure homogenization preceded by precipitation) by employing various stabilizers. Optimized ZTP-NS was characterized for particle size, solid state, morphology and solubility. In vitro drug release of ZTP and formulations was conducted using Franz diffusion cell. Stability study was performed at different temperature conditions. Pharmacokinetic study was performed in Wistar rats to determine the bioavailability and brain distribution of ZTP after intra-nasal (IN) and intravenous (IV) administration. Histopathology of brain was done after repeated administration of IN ZTP dispersion and NS up to 14 days. RESULTS:The optimized ZTP-NS formulated with Pluronic F-127 (0.3%w/v), Hydroxypropyl methyl cellulose E15 (0.3%w/v) and soya lecithin (0.4%w/v) showed particle size of 519.26 ± 10.44 nm & 330.2 ± 12.90 nm and zeta potential of -21.7 ± 1.39 mV and - 18.26 ± 1.64 mV with sonoprecipitation and combination technique respectively. In vitro drug release was high (81.79 ± 3.23%) for ZTP-NS prepared by combination technique. Intranasal NS resulted in high brain concentrations of 8.6 fold (sonoprecipitation) and 10.79-fold hike in AUC0-24h in contrast to intravenous ZTP solution. Histopathology results reveal no significant changes in brain microscopic images. CONCLUSION:ZTP-NS was successfully developed, characterized and found that nanosuspension is a favorable approach for intranasal delivery of zotepine. Graphical abstract Graphical abstract representing zotepine drawbacks, nanosuspension preparation, characterization and pharmacokinetic study in rats.

Project description:BackgroundMoxifloxacin is a bactericidal methoxyquinolone used for the treatment of conjunctivitis and prophylactic therapy in cataract and refractive surgeries. Chloramphenicol is a bacteriostatic organochlorine introduced into clinical practice in 1948 and used mainly in topical preparations because of its known toxicity.ObjectivesThe study aimed to evaluate the in vitro antibacterial effect and the ocular cytotoxicity of these broad-spectrum antibiotics.MethodsAntimicrobic activity was tested on 4 bacteria strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis), and determined through calculation of MIC and half inhibitory concentration for each microorganism. Antibacterial activity was determined by microdilution method after 24 hours' incubation with 2-fold serial dilutions (2.5 mg/mL to 4.883 µg/mL) of moxifloxacin and chloramphenicol. Disk diffusion test were performed according to European Committee on Antimicrobial Susceptibility Testing methodology. Biofilm formation inhibition and biofilm eradication concentration assay were conducted for P aeruginosa and S epidermidis using the microdilution method. Cytotoxicity of antibiotics was evaluated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) colorimetric assay on human corneal cell.ResultsCytotoxicity of antibiotics was evaluated on human epithelial corneal cells after 4 hours treatment by viability assay. Results showed that corneal cell viability was significantly higher after moxifloxacin treatment compared with chloramphenicol (P < 0.01). Moxifloxacin is characterized by a significantly lower MIC and half inhibitory concentration values and a larger inhibition zone for all the strain tested, with high performance in controlling gram-negative growth, compared with chloramphenicol. Moreover, moxifloxacin showed higher activity compared with chloramphenicol in the inhibition of biofilm formation and in the disruption of biofilm, especially against S epidermidis biofilm.ConclusionsThe lower corneal cell toxicity and the broader spectrum of antibacterial activity observed with moxifloxacin suggests its use in ophthalmic solution for the treatment of bacterial eye infections.

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An ion-paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection.

Publications

An ion-paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection.

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