Physicochemical Properties and In Vivo Assessment of Timolol-Loaded Poly(D,L-Lactide-co-Glycolide) Films for Long-Term Intraocular Pressure Lowering Effects

Abstract

Timolol-loaded poly(D,L-lactide-co-glycolide; PLGA) films were prepared for achieving the long-term intraocular pressure (IOP) lowering effect on glaucoma treatment. The physicochemical properties and in vivo effects of films were determined and characterize the delivery system. PLGA, span 20, propylene glycol (PG), and timolol base were dissolved in dichloromethane (DCM) and kept in a stainless mold; timolol films were prepared after the evaporation of DCM. Timolol disc-shape film preparation (TDF), containing 1 mg of timolol in 0.37 cm(2) area, was fabricated by using a trephine and placed onto the cul de sac of alpha-chymotrypsin-induced ocular hypertension rabbits for assessing the IOP lowering effect. The prepared films characterized a Young's modulus ranged from 1.13 to approximately 2.49 MPa, and related to the content percentages of PLGA, PG, and the residual DCM. The timolol film could maintain drug release for 1 week. Following a single-dose application in ocular hypertension rabbits, the prepared TDF could achieve a long-term IOP lowering effect and maintain the IOP change (in comparison with baseline) of approximately 7 mmHg within 1 week. The aqueous humor levels of timolol were low within a range of 0.8 to approximately 0.24 microg/mL for the initial 24 h and less than 0.15 microg/mL for 4-7 days. The investigated film formulation might be potentially developed for the application of long-term ocular delivery systems.

Optimization of Subconjunctival Biodegradable Microfilms for Sustained Drug Delivery to the Anterior Segment in a Small Animal Model

“…18 Polymeric systems have been used widely as implantable devices for controlled release of drugs in various organs. 19,20 In ophthalmic use, PLGA copolymers are used more commonly, for example, incorporating timolol for intraocular pressure control, 21 all-trans retinoic acid to reduce muscle adhesion in strabismus surgery, 22 cyclosporin for treatment of uveitis, 23 or 5-fluorouracil for antifibrotic effects. 24 In our study, we used PLC copolymers instead.…”

Contact Lenses for Drug Delivery

“…34 (Polymeric films have been used independently of contact lenses in ophthalmic drug delivery: timolol-PLGA films decrease the intraocular pressure when placed in the inferior fornix of the rabbit conjunctiva.) 35 We found that both the PLGA film and the HEMA hydrogel controlled the release of fluorescein separately and had additive effects. 28 Both fluorescein and ciprofloxacin could be released for weeks to months, with as much as a month of zeroorder kinetics.…”

The influence of additives in modulating drug delivery and degradation of PLGA thin films

“…Biodegradable polymers such as Poly( D,L -lactic-co-glycolic acid) (PLGA) are commonly used as drug delivery carriers owing to many favorable characteristics such as biodegradability, good biocompatibility and favorable mechanical properties. [1][2][3][4] In recent decades, PLGA has been widely studied for localized drug delivery in treating periodontal diseases, 5,6 glaucoma 7,8 and cancer 9,10 and to coat metallic stents 11,12 and fully biodegradable stents. 13,14 Various polymeric drug delivery systems have been investigated to optimize physicochemical properties, hydrolysis rates and drug release profiles to accommodate diverse biomedical treatments.…”