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  • Title: RETRACTED: Influence of choroidal neovascularization and biodegradable polymeric particle size on transscleral sustained delivery of triamcinolone acetonide.
    Author: Kadam RS, Tyagi P, Edelhauser HF, Kompella UB.
    Journal: Int J Pharm; 2012 Sep 15; 434(1-2):140-7. PubMed ID: 22633904.
    Abstract:
    PURPOSE: One objective of this study was to determine whether polymeric nanoparticles and/or microparticles sustain transscleral choroidal and retinal delivery of triamcinolone acetonide (TA) for two months in therapeutically effective concentrations after single periocular administration. Another objective of this study was to assess the influence of choroidal neovascularization on transscleral delivery of TA. METHODS: Polymeric nano- and micro-particles of TA were prepared by o/w emulsion-solvent evaporation method using poly-l-lactide (PLA). Particles were characterized for drug loading, size, surface morphology, and the in vitro drug release profile. Choroidal neovascularization (CNV) was induced in brown Norway (BN) rats using a 532 nm diode argon laser and the CNV induction was assessed using fluorescein angiography. In vivo delivery was assessed in control and CNV induced rats at 2 months after periocular injection of TA loaded nano- or micro-particle suspension, or plain TA suspension in PBS (pH 7.4). Ocular tissue levels of TA were estimated using LC-MS/MS following liquid-liquid extraction of drug from tissue samples. Nile red loaded microparticles entrapped in periocular tissue at the end of the study was visualized using scanning electron microscopy and confocal microscopy. Inhibitory effect of TA on VEGF secretion was evaluated in ARPE-19 cells. RESULTS: Triamcinolone acetonide-PLA nano- (551 nm) and micro-particles (2090 nm), with 14.7 and 29.5% drug loading, respectively, sustained in vitro TA release for about 45 and 120 days. After subconjunctival injection, microparticles were able to sustain the delivery in all intraocular tissues for 2 months; whereas no drug levels were detected for TA loaded nanoparticles and plain suspension of TA. Intraocular delivery of TA from microparticles was higher in CNV induced rats when compared to control rats. Significant amount of microparticles remained in periocular tissue at 2 months after injection, and maintained spherical shape. TA decreased VEGF secretion by 50% at 0.07 μM. At the end of the in vivo study, choroid-RPE and retina TA levels in CNV induced rats were 16- and 5-fold higher than the IC(50) for VEGF secretion. CONCLUSIONS: Single periocular injection of polymeric microparticles but not nanoparticles sustained effective levels of TA in choroid-RPE and retina for 2 months, with the TA delivery being greater in CNV induced rats than the control rats.
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