Purchase this article with an account.
R. S. Kadam, N. B. Shelke, U. B. Kompella; Microparticles for Sustained Intravitreal Delivery of TG-0054, A Drug Intended for Treating Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5329.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The short half-life of many drugs in the vitreous necessitates frequent injections. Such repeated injections can potentially cause endophthalmitis and retinal detachment. TG-0054 is a highly water soluble, low molecular weight drug that has shown beneficial effects in treating choroidal neovascularization in mouse models. The purpose of the current study was to develop biodegradable microparticles for sustained delivery of TG-0054 to the back of the eye for at least six months
Polymeric microparticles of TG-0054 were prepared using an emulsion-solvent evaporation technique by varying the types of polymers and the nature of the dispersion medium. The microparticles were characterized for drug content, particle size (dynamic light scattering), morphology (scanning electron microscopy), and residual solvent (GC-MS). In vitro drug release studies were carried out up to 6 months in PBS (37 0C). In vivo drug delivery from a selected microparticles formulation (dose equivalent to 1.5 mg of drug/animal) and plain drug solution in PBS (1.0 mg/animal) was assessed at the end of 1 and 3 months after intravitreal injections (50 µl) in New Zealand rabbits. Drug analysis during in vitro and in vivo studies was done using UV spectrophotometer and liquid chromatography-mass spectrometer (LC-MS), respectively.
Polylactide based microparticle formulation provided good drug loading (10-15%), micron size spherical particles (mean size: 7-9 µm) with a polydispersity index of 0.10-0.27, and low residual solvent content (≈ 1 ppb). In vitro release study with the optimized formulation indicated low burst release during the initial 24 hrs (< 20%), followed by sustained drug release during a study period of six months. In vivo experiments showed sustained drug release for microparticles. When compared with microparticles, drug solution showed very low levels (< 5 µg/g) in all assessed tissues at the end of one month, and there were no detectable drug levels at the end of three months. Microparticles showed sustained and steady drug levels in retina at one month (244 µg/g) and three months (243 µg/g). Lower, but similarly sustained drug levels were observed in choroid-RPE at one month (33.9 µg/g) and three months (62.8µg/g). Vitreous drug levels were 28.1 µg/g at one month and 43.7 µg/g at three months. Plasma levels were below the limit of detection (< 25 ng/ml).
An intravitreally injectable polylactide based microparticle is a viable option for sustained delivery of TG-0054 to the posterior segment of the eye.
This PDF is available to Subscribers Only