Hydrogels can potentially prolong the release of a therapeutic protein, especially to treat blinding conditions. One challenge is to ensure that the protein and hydrogel are intimately mixed by better protein entanglement within the hydrogel. N-isopropylacrylamide (NIPAAM) gels are optimized with poly(ethylene glycol) diacrylate (PEDGA) crosslinker in the presence of either bevacizumab or PEG conjugated ranibizumab (PEG -Fab ). The release profiles of the hydrogels are evaluated using an outflow model of the eye, which is previously validated for human clearance of proteins. Release kinetics of in situ loaded bevacizumab-NIPAAM gels displays a prolonged bimodal release profile in phosphate buffered saline compared to bevacizumab loaded into a preformed NIPAAM gel. Bevacizumab release in simulated vitreous from in situ loaded gels is similar to bevacizumab control indicating that diffusion through the vitreous rather than from the gel is rate limiting. Ranibizumab is site-specifically PEGylated by disulfide rebridging conjugation. Prolonged and continuous release is observed with the in situ loaded PEG -Fab -NIPAAM gels compared to PEG -Fab injection (control). Compared to an unmodified protein, there is better mixing due to PEG entanglement and compatibility of PEG -Fab within the NIPAAM-PEDGA hydrogel. These encouraging results suggest that the extended release of PEGylated proteins in the vitreous can be achieved using injectable hydrogels.

A BSTRACT Oral mucositis (OM) is an extremely serious and challenging complication of chemoradiotherapy, which may limit the efficacy of cancer treatment. Complications related to OM include potential nutrition impairment, high economic burden, and negative impacts on patients’ quality of life. Current therapeutic options with local traditional pharmaceutical formulations are largely focused on controlling symptoms, and only few agents are available for treatment. Several local supportive and palliative agents are used for the prevention of OM; however, a standard treatment for the disease has not been confirmed yet. The efficacy of treatment could be improved through the introduction of new medical agents with updated dosage forms that can enhance and optimize local drug delivery and create greater therapeutic effects with fewer side effects. The focus of this review was to provide clear and direct information about the currently available topical therapeutic agents in clinical practice used to cure and/or reduce the incidence of ulcerative symptoms of OM, excluding the associated pain and other coexisting complications such as bacterial and fungal infections. The review also provides recent evidences regarding agents that could be used as promising novel therapies in updated local delivering systems. This will support further encouraging options and approaches for the management of OM and will improve compliance that could be translated in better disease control and survival.

There is a need to prolong drug residence time using a biocompatible formulation in the subconjunctival space after surgery to treat glaucoma. Drug releasing discs were prepared with 2-(hydroxyethyl)methacrylate (HEMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC). The ratio of bound water (Wb) to free water (Wf) ratio increased from 1:0.3 to 1:6.8 with increasing MPC (0 to 50%, w/w). The optimal balance between water content, SR and mechanical strength were obtained with 10% MPC (w/w) hydrogels. Water-alcohol mixtures were examined to facilitate loading of poorly soluble drugs, and they showed greater hydrogel swelling than either water or alcohol alone. The SR was 1.2 ± 0.02 and 3.3 ± 0.1 for water and water:ethanol (1:1) respectively. HEMA-MPC (10%) discs were loaded with dexamethasone using either water:ethanol (1:1) or methanol alone. Drug release was examined in an outflow rig model that mimics the subconjunctival space in the eye. Dexamethasone loading increased from 0.3 to 1.9 mg/disc when the solvent was changed from water:ethanol (1:1) to methanol with the dexamethasone half-life (t½) increasing from 1.9 to 9.7 days respectively. These encouraging results indicate that HEMA-MPC hydrogels have the potential to sustain the residence time of a drug in the subconjunctival space of the eye.