Controlled Release of Thermosensitive Hydrogel Incorporating Betaxolol-Loaded Resin Microspheres for Glaucoma Therapy

Glaucoma therapy is often limited by poor ocular bioavailability and the short residence time of conventional eye drops, highlighting the need for sustained-release delivery systems. This study presents the development of a thermosensitive in situ hydrogel incorporating cation-exchange resin (CER) for sustained delivery of betaxolol hydrochloride (BH) in glaucoma therapy. CER microspheres were prepared using a seed swelling method, and drug loading was achieved through an ion-exchange interaction to obtain BH@CER, which was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). A thermosensitive hydrogel-microspheres composite (BH@CER@P407) was formulated using optimized concentrations of poloxamer 407 (P407), exhibiting a sol-to-gel transition at approximately 34°C for easy administration and prolonged ocular retention. In vitro release studies indicated that BH@CER@P407 achieved sustained release (85% over 12 h), in contrast to the pronounced burst release of commercial BH eye drops (Betoptic® S, 90% within 2 h). In vivo evaluations in New Zealand rabbits revealed strong ocular adhesion and retention for up to 8 h, correlating with sustained intraocular pressure (IOP) reduction. Ocular irritation studies confirmed excellent biocompatibility. Compared to Betoptic® S, the BH@CER@P407 offers enhanced ocular residence and prolonged therapeutic efficacy, presenting a promising strategy for improving glaucoma treatment.  Graphical