Development and optimization of an ocular hydrogel adhesive patch using definitive screening design (DSD).

Adhesive hydrogels based on chemically modified photocrosslinkable polymers with specific physicochemical properties are frequently utilized for sealing wounds or incisions. These adhesive hydrogels offer tunable characteristics such as tailorable tissue adhesion, mechanical properties, swelling ratios, and enzymatic degradability. In this study, we developed and optimized a photocrosslinkable adhesive patch, GelPatch, with high burst pressure, minimal swelling, and specific mechanical properties for application as an ocular (sclera and subconjunctival) tissue adhesive. To achieve this, we formulated a series of hydrogel patches composed of different polymers with various levels of methacrylation, molecular weights, and hydrophobic/hydrophilic properties. A computerized multifactorial definitive screening design (DSD) analysis was performed to identify the most prominent components impacting critical response parameters such as adhesion, swelling ratio, elastic modulus, and second order interactions between applied components. These parameters were mathematically processed to generate a predictive model that identifies the linear and non-linear correlations between these factors. In conclusion, an optimized formulation of GelPatch was selected based on two modified polymers: gelatin methacryloyl (GelMA) and glycidyl methacrylated hyaluronic acid (HAGM). The ex vivo results confirmed adhesion and retention of the optimized hydrogel subconjunctivally and on the sclera for up to 4 days. The developed formulation has potential to be used as an ocular sealant for quick repair of laceration type ocular injuries.

Ketanserin attenuates nicotine-induced working memory improvement in rats.

Nicotinic systems have been shown in numerous studies to be important for spatial working memory. Nicotinic systems are certainly not acting alone in the basis of memory function, but act in concert with a variety of other neural systems. Important for these interactions is nicotinic induced release of a variety of neurotransmitters involved in memory function including serotonin (5-HT). We have found that the 5-HT2 receptor antagonist, ketanserin, effectively attenuated nicotine-induced attentional improvement. The current study explored the interaction between nicotinic and serotonergic systems in the performance of a spatial working memory task in the radial-arm maze. Female Sprague-Dawley rats were trained on the win-shift working memory task on the 8-arm radial maze. After 18 sessions of acquisition training the rats were given acute doses of nicotine (0.2 and 0.4 mg/kg), ketanserin (0.5, 1 and 2 mg/kg) or combinations of the two. The vehicle served as the control. As seen in previous studies, nicotine caused a significant improvement in working memory performance as indexed by the number of correct arm entries before the first error (entries to repeat). Ketanserin at the doses tested did not cause a significant effect on choice accuracy, but it did significantly attenuate the improvement caused by the 0.2 mg/kg nicotine dose. The higher 0.4 mg/kg nicotine dose was nearly sufficient to overcome the ketanserin effect. This study shows that, as with attentional function, nicotine-induced working memory improvement is attenuated by the 5-HT2 antagonist ketanserin. Given that many antipsychotic drugs have substantial 5-HT2 antagonist effects, these atypical antipsychotic drugs may reduce the cognitive improvements caused by nicotinic treatments.