Screening of Polymer Additives in Poloxamer 407 Hydrogel Formulations for Intravesical Instillation: Evaluation of Mechanical Properties, Gel-forming Capacity, and Drug Release

Poloxamer 407 (PLX) hydrogel has been used as a drug delivery system for intravesical instillation, but it has a limitation of insufficient gel strength. Here, to modulate the viscosity and strength of hydrogel, various polymers were screened. Their effect on viscosity decreased in the following order: high molecular-weight hyaluronic acid (HHA; 33.524 Pa.s) > hydroxypropyl methylcellulose > chitosan > low-molecular weight HA > sodium alginate > carbopol (24.332 Pa. s). Polymer addition hardly altered the thermo-reversible property of hydrogels; the gelation temperature was 21.0-25.3 degrees C and gelation time was 17.28-28.32 s. With gemcitabine as a water-soluble ingredient, gel erosion and drug release were examined using an in vitro bladder simulation model. After four repeated cycles of filling and emptying, the remaining fraction of HHA-added hydrogel and PLX hydrogel was 74.6% and 57.8%, respectively. Furthermore, drug release was diffusion- and erosion-controlled. Thus, HHA-added hydrogel is a promising system for intravesical instillation.