Controlled PVA Release from Chemical-Physical Interpenetrating Networks to Treat Dry Eyes

Abstract

Dry eye disease is becoming increasingly prevalent, and lubricating eye drops, a mainstay of its treatment, have a short duration of time on the ocular surface. Although there are various drug delivery methods to increase the ocular surface residence time of a topical lubricant, the main problem is the burst release from these delivery systems. To overcome this limitation, herein, a chemical-physical interpenetrating network (IPN) was fabricated to take control over the release of poly(vinyl alcohol) (PVA), a well-known therapeutic agent used to stabilize tear film, from gelatin methacrylate (GelMA) hydrogels. In this report, PVA was specifically used as part of a GelMA-based polymeric hydrogel owing to its physical cross-linking ability via a simple freeze-thaw method. The interpenetrating polymer network was fabricated in a sequential manner where GelMA was chemically cross-linked by photo-cross-linking, followed by physical cross-linking of PVA using a relatively short freeze-thaw cycle. Interestingly, upon applying only one short freeze-thaw cycle (of 1 or 2 h), the crystalline domains in PVA were increased in the interpenetrating network. The endothermic peaks at 48 and 60 °C in differential scanning calorimetry (DSC) thermograms and 20°-2θ peaks in X-ray diffraction (XRD) patterns suggest the presence of these crystalline domains. With the help of a suite of characterization, we further delineate the role of freeze-thaw cycles in taking control over the release of PVA. The release profiles of the PVA-containing hydrogels showed highest linearity with the Korsmeyer-Peppas model (0.9944 < R2 < 0.9952), indicating that these systems follow non-Fickian or anomalous transport.