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.
Highlights
The ongoing coronavirus disease 2019 (COVID-19) pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a β-coronavirus within the family Coronaviridae [1]
For a more detailed description, the CH2 component peak of poly(ethylene glycol) (PEG) was located at 3.64 ppm, and proton signals of polypropylene glycol (PPG) were located at 3.56–3.39 ppm, while overlapped peaks at 1.14–1.22 ppm were assigned to middle -CH2 of Se monomer
Despite the low concentration, we found a consistent increase in the RDV/poly(DHSe/PEG/PPG urethane) hydrogel formulation
Summary
The ongoing coronavirus disease 2019 (COVID-19) pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a β-coronavirus within the family Coronaviridae [1]. The potential of SARS-CoV-2 to infect the ocular epithelia and mucosa has been highlighted through ocular surface exposure to pollutants and the virus [4]. Considering that the ocular tissues exhibit an anatomical proximity to the respiratory tract, viruses can lead to ocular complications and further cause acute respiratory infection [5,6]. Documented reports of the distribution of angiotensin-converting enzyme 2 (ACE2) receptors and transmembrane protease serine 2 (TMPRSS2) protein in ocular tissues brought insights into the potential of SARS-CoV-2 to invade the anterior eye segment [6,7]. The susceptible population may be exposed to COVID-19 by touching the eyes with possibly
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