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Thermosensitive Poly(DHSe/PEG/PPG Urethane)-Based Hydrogel Extended Remdesivir Application in Ophthalmic Medication.

ABSTRACT: The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.

SUBMITTER: Xu S

PROVIDER: S-EPMC8778792 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The purpose of this work was to investigate the effect of multifunctionality on material properties of synthetic polymer aerogels. For this purpose, we present the synthesis and characterization of monolithic dendritic-type urethane-acrylate monomers based on an aliphatic/flexible (Desmodur N3300), or an aromatic/rigid (Desmodur RE) triisocyanate core. The terminal acrylate groups (three at the tip of each of the three branches, nine in total) were polymerized with 2,2'-azobis(isobutyronitrile) (AIBN) via free radical chemistry. The resulting wet-gels were dried with supercritical fluid (SCF) CO₂. Aerogels were characterized with ATR-FTIR and solid-state 13C NMR. The porous network was probed with N₂-sorption and scanning electron microscopy (SEM). The thermal stability of aerogels was studied with thermogravimetric analysis (TGA). Most aerogels were macroporous materials (porosity > 80%), with high thermal stability (up to 300 °C). Aerogels were softer at low monomer concentrations and more rigid at higher concentrations. The material properties were compared with those of analogous aerogels bearing only one acrylate moiety at the tip of each branch and the same cores, and with those of analogous aerogels bearing norbornene instead of acrylate moieties. The nine-terminal acrylate-based monomers of this study caused rapid decrease of the solubility of the growing polymer and made possible aerogels with much smaller particles and much higher surface areas. For the first time, aliphatic/flexible triisocyanate-based materials could be made with similar properties in terms of particle size and surface areas to their aromatic/rigid analogues. Finally, it was found that with monomers with a high number of crosslinkable groups, material properties are determined by multifunctionality and thus aerogels based on 9-acrylate- and 9-norbornene-terminated monomers were similar. Materials with aromatic cores are carbonizable with satisfactory yields (20⁻30% w/w) to mostly microporous materials (BET surface areas: 640⁻740 m² g-1; micropore surface areas: 360⁻430 m² g-1).

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Thermosensitive Poly(DHSe/PEG/PPG Urethane)-Based Hydrogel Extended Remdesivir Application in Ophthalmic Medication.

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