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1.
Int J Pharm ; 659: 124265, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38795935

ABSTRACT

Metformin (MET) can be an alternative therapeutic strategy for managing ocular burn primarily because of its pleiotropic mechanism. Longer retention on the ocular surface and sustained release are necessary to ensure the efficacy of MET for ocular application. Although the high aqueous solubility of MET is good for formulation and biocompatibility, it makes MET prone to high nasolacrimal drainage. This limits ocular residence and may be a challenge in its application. To address this, polymers approved for ophthalmic application with natural origin were analyzed through in silico methods to determine their ability to bind to mucin and interact with MET. An ocular insert of MET (3 mg/6 mm) was developed using a scalable solvent casting method without using preservatives. The relative composition of the insert was 58 ± 2.06 %w/w MET with approximately 14 %w/w tamarind seed polysaccharide (TSP), and 28 %w/w propylene glycol (PG). Its stability was demonstrated as per the ICH Q1A (R2) guidelines. Compatibility, ocular retention, drug release, and other functional parameters were evaluated. In rabbits, efficacy was demonstrated in the 'corneal alkali burn preclinical model'. TSP showed potential for mucoadhesion and interaction with MET. With adequate stability and sterility, the insert contributed to adequate retention of MET (10-12 h) in vivo and slow release (30 h) in vitro. This resulted in significant efficacy in vivo.


Subject(s)
Delayed-Action Preparations , Drug Liberation , Eye Burns , Metformin , Polysaccharides , Seeds , Tamarindus , Animals , Metformin/chemistry , Metformin/administration & dosage , Rabbits , Tamarindus/chemistry , Polysaccharides/chemistry , Seeds/chemistry , Eye Burns/drug therapy , Eye Burns/chemically induced , Administration, Ophthalmic , Drug Implants , Male , Burns, Chemical/drug therapy , Drug Stability , Corneal Injuries/drug therapy , Cornea/metabolism , Cornea/drug effects , Propylene Glycol/chemistry , Solubility
2.
JMIR Res Protoc ; 9(10): e23241, 2020 Oct 30.
Article in English | MEDLINE | ID: mdl-33124993

ABSTRACT

BACKGROUND: India has the largest burden of drug­resistant organisms compared with other countries around the world, including multiresistant and extremely drug­resistant tuberculosis and resistant Gram­negative and Gram­positive bacteria. Antibiotic resistant bacteria are found in all living hosts and in the environment and move between hosts and ecosystems. An intricate interplay of infections, exposure to antibiotics, and disinfectants at individual and community levels among humans, animals, birds, and fishes triggers evolution and spread of resistance. The One Health framework proposes addressing antibiotic resistance as a complex multidisciplinary problem. However, the evidence base in the Indian context is limited. OBJECTIVE: This multisectoral, trans-species surveillance project aims to document the infection and resistance patterns of 7 resistant-priority bacteria and the risk factors for resistance following the One Health framework and geospatial epidemiology. METHODS: This hospital- and community-based surveillance adopts a cross-sectional design with mixed methodology (quantitative, qualitative, and spatial) data collection. This study is being conducted at 6 microbiology laboratories and communities in Khurda district, Odisha, India. The laboratory surveillance collects data on bacteria isolates from different hosts and their resistance patterns. The hosts for infection surveillance include humans, animals (livestock, food chain, and pet animals), birds (poultry), and freshwater fishes (not crustaceans). For eligible patients, animals, birds and fishes, detailed data from their households or farms on health care seeking (for animals, birds and fishes, the illness, and care seeking of the caretakers), antibiotic use, disinfection practices, and neighborhood exposure to infection risks will be collected. Antibiotic prescription and use patterns at hospitals and clinics, and therapeutic and nontherapeutic antibiotic and disinfectant use in farms will also be collected. Interviews with key informants from animal breeding, agriculture, and food processing will explore the perceptions, attitudes, and practices related to antibiotic use. The data analysis will follow quantitative (descriptive and analytical), qualitative, and geospatial epidemiology principles. RESULTS: The study was funded in May 2019 and approved by Institute Ethics Committees in March 2019. The data collection started in September 2019 and shall continue till March 2021. As of June 2020, data for 56 humans, 30 animals and birds, and fishes from 10 ponds have been collected. Data analysis is yet to be done. CONCLUSIONS: This study will inform about the bacterial infection and resistance epidemiology among different hosts, the risk factors for infection, and resistance transmission. In addition, it will identify the potential triggers and levers for further exploration and action. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23241.

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