Bimatoprost-Loaded Ocular Inserts as Sustained Release Drug Delivery Systems for Glaucoma Treatment: In Vitro and In Vivo Evaluation

Abstract

The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP) was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a promising system for glaucoma management.

The Effect of β-Glycerophosphate Crosslinking on Chitosan Cytotoxicity and Properties of Hydrogels for Vaginal Application

“…Unmodified CS, CS/lGP, and CS/hGP at different concentrations were diluted in cell culture medium at 37˝C for 1 h. The pH of the medium with samples varied in the range between 6.72 (for unmodified CS) to 7.55 (for CS/hGP formulations). Afterwards, there were added to a six-well plates containing 4ˆ10 5 per well CRL 2616 confluent cells and incubated for 4 h at 37˝C in a 5% CO 2 humidified atmosphere. Then the culture medium was discarded, cells were rinsed three times with phosphate buffered saline (PBS) and then incubated for 4 h in 1 mL of MTT solution (0.5 mg¨mL´1 of PBS) at 37˝C.…”

“…In the recent years, mucoadhesive delivery systems providing intimate contact between a dosage form and the vaginal mucosa have gained a great attention [3,4]. Among mucoadhesive polymers, chitosan (CS) is extensively studied in designing ocular [5], buccal [6], nasal [7], and vaginal dosage forms [8,9]. In addition, CS is currently receiving great interest in pharmaceutical and biomedical fields, particularly because of its penetration enhancement capability [10,11] and antifungal activity [12][13][14].…”

Liposomes as a Novel Ocular Delivery System for Brinzolamide: In Vitro and In Vivo Studies

“…Each formulation (50 μL) was instilled topically into the upper quadrant of the right eye, and the IOP was measured at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 h using Tono-Pen XL® tonometer (Reichert Technologies, NY, USA) after drug administration. IOP was also measured in the undosed left eye at all mentioned time intervals according to literature (11,12).…”

Why Do People (Still) Go Blind from Glaucoma?

“…102 In another study, prostaglandin-loaded inserts were administered into the conjunctival sac of rats and resulted in significant IOP lowering with decreased RGC loss compared to controls. 103 There are ongoing clinical trials testing the safety and efficacy of these new drug delivery systems in humans and we expect these alternatives to better control IOP variability and slow progression in the near future. glaucoma pathogenesis to advances in diagnosis and treatment.…”