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Thermogels containing sulfated hyaluronan as novel topical therapeutics for treatment of ocular surface inflammation.

ABSTRACT: The development of long lasting therapeutic agents is critically important for efficient treatment of chronic diseases. We herein report a rational strategy to develop a therapeutic thermogel featured with prolonged anti-inflammatory and corneal-protective effects. Specifically, a hyaluronic acid with different sulfation degrees and an amine-terminated poly(N-isopropylacrylamide) are conjugated to achieve the thermogels. In vitro studies reveal that the thermogels are highly biocompatible to statens seruminstitut rabbit cornea cells and their anti-inflammatory properties are strongly dependent on the sulfation degree. In a rabbit model of ocular inflammation, single-dose topical administration of a thermogel formulation could repair defects in corneal epithelium (∼99% thickness restored), prevent corneal cell apoptosis (∼68.3% cells recovered), and suppress ocular surface inflammation (∼4-fold decrease) for a follow-up period of 7 days. This high treatment efficacy of the thermogel can be attributed to its potent inhibition in selectin-mediated leukocyte infiltration as well as effective corneal protection. These findings show a great promise for topical treatment of ocular inflammation and advancement of ophthalmic formulations using the bioactive thermogel as a therapeutic component that is not rapidly cleared from the eye and thus considerably reduces administration times.

SUBMITTER: Nguyen DD

PROVIDER: S-EPMC8649391 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The ocular surface microbiome of veterinary species has not been thoroughly characterized using molecular-based techniques, such as next generation sequencing (NGS), as the vast majority of studies have utilized traditional culture-based techniques. To date, there is one pilot study evaluating the ocular surface of healthy dogs using NGS. Furthermore, alterations in the ocular surface microbiome over time and after topical antibiotic treatment are unknown. The objectives of this study were to describe the bacterial composition of the ocular surface microbiome in clinically normal dogs, and to determine if microbial community changes occur over time or following topical antibiotic therapy. Topical neomycin-polymyxin-bacitracin ophthalmic ointment was applied to one eye each of 13 adult dogs three times daily for seven days, while contralateral eyes served as untreated controls. The inferior conjunctival fornix of both eyes was sampled via swabbing at baseline prior to antibiotic therapy (day 0), after 1 week of treatment (day 7), and 4 weeks after discontinuing treatment (day 35). Genomic DNA was extracted from the conjunctival swabs and primers targeting the V4 region of bacterial 16S rRNA genes were used to generate amplicon libraries, which were then sequenced on an Illumina platform. Data were analyzed using Quantitative Insights Into Molecular Ecology (QIIME 2.0). At baseline, the most relatively abundant phyla sequenced were Proteobacteria (49.7%), Actinobacteria (25.5%), Firmicutes (12%), Bacteroidetes (7.5%), and Fusobacteria (1.4%). The most common families detected were Pseudomonadaceae (13.2%), Micrococcaceae (12%), Pasteurellaceae (6.9%), Microbacteriaceae (5.2%), Enterobacteriaceae (3.9%), Neisseriaceae (3.5%), and Corynebacteriaceae (3.3%). Alpha and beta diversity measurements did not differ in both control and treatment eyes over time. This report examines the temporal stability of the canine ocular surface microbiome. The major bacterial taxa on the canine ocular surface remained consistent over time and following topical antibiotic therapy.

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Thermogels containing sulfated hyaluronan as novel topical therapeutics for treatment of ocular surface inflammation.

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