RESUMO
OBJECTIVE: Drug delivery to ocular tissues is challenging due to rapid removal of instilled drug due to low resident time in ocular tissues. The aim of the study was to formulate an ophthalmic emulgel that delivers two drugs (betamethasone sodium phosphate [BSP] and levofloxacin). The new combination will allow the simultaneous administration and extended release of the two drugs which potentially improve resident time in ocular tissues, patient compliance, and adherence to treatment. MATERIALS AND METHODS: Formulations containing different gelling agents at different concentrations were prepared to choose the optimum combination regarding physical properties and release. The emulgel formulations F1, F2, F3, and F4 were made using gelling agent 1% and 2% xanthan gum, 1% carbopole 934, and 2% methyl cellulose, respectively. F5 was formulated using 2% methyl cellulose with double the amount of poloxamer 188 as emulsifying agent. All the formulations were examined regarding their physical appearance, pH, viscosity, drug content, and in vitro drug release. The optimum formula was also examined for antibacterial activity. RESULTS: The results demonstrated that F5 was the optimum formulation having a proper physical characteristics and release profile of both drugs, 96% and 90% for BSP and levofloxacin, respectively, compared to other formulations and commercial eye drops. CONCLUSION: Simultaneous and extended release of the two drugs was achieved using one formulation of emulgel. The ability to deliver hydrophilic and hydrophobic drug through the same formulation without the need to use two drops will improve patient compliance and hence patient adherence to treatment.
RESUMO
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.
RESUMO
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 (PEG10 -Fabrani ). 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 PEG10 -Fabrani -NIPAAM gels compared to PEG10 -Fabrani injection (control). Compared to an unmodified protein, there is better mixing due to PEG entanglement and compatibility of PEG10 -Fabrani 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.
