Controlled PVA\nRelease from Chemical–Physical\nInterpenetrating Networks to Treat Dry Eyes

Dry eye disease is becoming increasingly prevalent, and\nlubricating\neye drops, a mainstay of its treatment, have a short duration of time\non the ocular surface. Although there are various drug delivery methods\nto increase the ocular surface residence time of a topical lubricant,\nthe main problem is the burst release from these delivery systems.\nTo overcome this limitation, herein, a chemical–physical interpenetrating\nnetwork (IPN) was fabricated to take control over the release of poly(vinyl\nalcohol) (PVA), a well-known therapeutic agent used to stabilize tear\nfilm, from gelatin methacrylate (GelMA) hydrogels. In this report,\nPVA was specifically used as part of a GelMA-based polymeric hydrogel\nowing to its physical cross-linking ability via a simple freeze-thaw\nmethod. The interpenetrating polymer network was fabricated in a sequential\nmanner where GelMA was chemically cross-linked by photo-cross-linking,\nfollowed by physical cross-linking of PVA using a relatively short\nfreeze-thaw cycle. Interestingly, upon applying only one short freeze-thaw\ncycle (of 1 or 2 h), the crystalline domains in PVA were increased\nin the interpenetrating network. The endothermic peaks at 48 and 60\n°C in differential scanning calorimetry (DSC) thermograms and\n20°–2θ peaks in X-ray diffraction (XRD) patterns\nsuggest the presence of these crystalline domains. With the help of\na suite of characterization, we further delineate the role of freeze-thaw\ncycles in taking control over the release of PVA. The release profiles\nof the PVA-containing hydrogels showed highest linearity with the\nKorsmeyer–Peppas model (0.9944 < <i>R</i><sup>2</sup> < 0.9952), indicating that these systems follow non-Fickian\nor anomalous transport.