Improvement in Ocular Bioavailability and Prolonged Delivery of Tobramycin Sulfate Following Topical Ophthalmic Administration of Drug-Loaded Mucoadhesive Microparticles Incorporated in Thermosensitive In Situ Gel.

PURPOSE: Conventional topical delivery in hyperacute bacterial conjunctivitis and endophthalmitis is associated with low drug bioavailability due to rapid precorneal clearance. Hence, in the present investigation, an attempt has been made to enhance ocular bioavailability of tobramycin sulfate by formulating drug-loaded microparticles dispersed in thermosensitive in situ gel. METHODS: Microparticles prepared by emulsion-ionic gelation technique were characterized for drug loading, entrapment efficiency, particle size, surface morphology, and in vitro drug release. Consequently microparticles (F2 prepared with 1.5%w/v chitosan, 0.2%w/v tripolyphosphate, and drug, 30%w/w of polymer) with high drug loading and encapsulation efficiency were dispersed in thermosensitive in situ gel containing poloxamer 407 and varying percentage of chitosan. In situ gel containing drug-loaded microparticles were evaluated for gelation temperature, rheological behavior, mucoadhesive strength, in vitro drug release, in vitro permeation, ocular irritation, and bioavailability in aqueous humor of rabbits. RESULTS: Formulation containing 17%w/v poloxamer 407 and 0.5%w/v chitosan (P2) gelled at 32°C ± 1.5°C gave pseudoplastic behavior. In vitro permeability of tobramycin from the formulation P2 was found 2-folds greater than eye drops. It also gave significantly higher aqueous humor concentration of tobramycin compared with eye drops with no signs of ocular irritation. CONCLUSION: Thus, the formulation possesses high potential for treating ocular infections.

New endothelial keratoplasty, phacoemulsification, and intraocular lens implantation triple procedure: comparison with conventional triple procedure.

PURPOSE: To compare the clinical outcomes of a new triple procedure comprising endothelial keratoplasty, phacoemulsification, and intraocular lens (IOL) implantation and a conventional triple procedure comprising penetrating keratoplasty, extracapsular cataract extraction, and IOL implantation. SETTING: Cornea Services, Medical Research Foundation, Chennai, Tamil Nadu, India. METHODS: In this prospective nonrandomized study, the new triple procedure was performed in eyes with predominant endothelial dysfunction and coexisting cataract and the conventional triple procedure, in eyes with opacities affecting other layers of the cornea. Outcome measures were intraoperative and postoperative complications, 3-month postoperative distance visual acuity, refractive status, mean corneal power, corneal topography, and endothelial cell loss. The outcomes in the 2 groups were compared. RESULTS: The new procedure group comprised 54 eyes and the conventional procedure group, 26 eyes. All grafts in both groups were clear 3 months postoperatively. The IOL was fixated in the capsular bag in all eyes in the new procedure group and 23% of eyes in the conventional procedure group. Postoperatively, persistent epithelial defects, uveitis, glaucoma, and posterior capsule opacification were significantly more frequent in the conventional procedure group. Visual acuity was significantly better and the postoperative refractive status more predictable in the new procedure group. Endothelial cell loss was greater in the new procedure group than in the conventional group, although the difference was not statistically significant. CONCLUSION: The new triple procedure was safer than the conventional triple procedure and resulted in better visual outcomes, a more predictable refractive error, a smoother corneal contour, and a tectonically stronger globe. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.