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Periocular particulate systems: Disp...

University of Nebraska Medical Center.

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Periocular particulate systems: Disposition safety and efficacy.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Periocular particulate systems: Disposition safety and efficacy./
作者:	Amrite, Aniruddha C.
面頁冊數:	325 p.
附註:	Adviser: Uday B. Kompella.
Contained By:	Dissertation Abstracts International68-11B.
標題:	Health Sciences, Ophthalmology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3289618
ISBN:	9780549324676

Periocular particulate systems: Disposition safety and efficacy.
Amrite, Aniruddha C.

Periocular particulate systems: Disposition safety and efficacy. - 325 p.

Adviser: Uday B. Kompella.

Thesis (Ph.D.)--University of Nebraska Medical Center, 2007.

Choroidal neovascularization (CNV) associated with age related macular degeneration (ARMD) and diabetic retinopathy are leading causes of blindness. Vascular endothelial growth factor (VEGF) contributes significantly to the pathophysiology of these two disorders and anti-VEGF drugs are valuable in the treatment of the above disorders. However, the main hurdle in the treatment of these disorders is safe and effective delivery of therapeutic agents for prolonged periods to the retina or choroid; the target tissues. Among the various routes for drug delivery to the retina, the topical and intravenous routes are ineffective requiring high doses; efficacy of intravitreal route is limited with several complications that compromise vision; periocular routes, which allow transscleral retinal drug delivery, are safer alternatives to the intravitreal route but their clinical efficacy has yet to be fully established.

ISBN: 9780549324676Subjects--Topical Terms:

1019445
Health Sciences, Ophthalmology.

Periocular particulate systems: Disposition safety and efficacy.
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245 1 0 $a Periocular particulate systems: Disposition safety and efficacy.
300 $a 325 p.
500 $a Adviser: Uday B. Kompella.
500 $a Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7266.
502 $a Thesis (Ph.D.)--University of Nebraska Medical Center, 2007.
520 $a Choroidal neovascularization (CNV) associated with age related macular degeneration (ARMD) and diabetic retinopathy are leading causes of blindness. Vascular endothelial growth factor (VEGF) contributes significantly to the pathophysiology of these two disorders and anti-VEGF drugs are valuable in the treatment of the above disorders. However, the main hurdle in the treatment of these disorders is safe and effective delivery of therapeutic agents for prolonged periods to the retina or choroid; the target tissues. Among the various routes for drug delivery to the retina, the topical and intravenous routes are ineffective requiring high doses; efficacy of intravitreal route is limited with several complications that compromise vision; periocular routes, which allow transscleral retinal drug delivery, are safer alternatives to the intravitreal route but their clinical efficacy has yet to be fully established.
520 $a The aim of this research was to determine the anti-VEGF and anti-proliferative activity of celecoxib (a selective Cox-2 inhibitor; anti-inflammatory drug) and to understand the disposition of small molecule drugs like celecoxib, and sustained release delivery devices like nanoparticles and microparticles after periocular administration. We further assessed the safety and efficacy of sustained release celecoxib-poly(lactide-co-glycolide) (PLGA) microparticles for the treatment of diabetic retinopathy.
520 $a The results of the study demonstrated that celecoxib has anti-proliferative effects on choroidal endothelial and retinal pigment epithelial cells, in addition to its anti-VEGF effects on retinal pigment epithelial cells. Further, the anti-proliferative effects of celecoxib were independent of its Cox-2 inhibitory activity. Pharmacokinetic modeling indicated rapid clearance of celecoxib from the site of administration with a suspension formulation, indicating the need for a sustained release system. The disposition of particulate delivery systems from the periocular tissue is particle size dependent. Very small particles (20 nm) are cleared rapidly by the blood circulation and/or lymphatics. Particles in the range 200-2000 nm are retained at the periocular site of administration for at least two months and can be used as sustained delivery devices for transscleral retinal drug delivery. Periocular celecoxib-PLGA microparticles sustained drug release in vitro, a single injection of celecoxib-PLGA microparticles provided therapeutic drug levels in the retina for at least 2 months and inhibited diabetes induced elevations in retinal PGE2 secretion, VEGF protein, vitreous/plasma protein ratio, and blood retinal barrier leakage by 40, 50, 40, and 50%, respectively. The particulate delivery system did not cause any histological damage to the periocular tissue or the retina and did not alter blood cell counts or blood clinical chemistry.
520 $a In summary, therapeutically effective retinal drug delivery can be sustained for prolonged periods using periocular polymeric particulate delivery systems. Celecoxib-PLGA microparticles sustain retinal drug delivery for at least two months and ameliorate complications of diabetic retinopathy. They are also of potential value in treating CNV associated with ARMD.
590 $a School code: 0367.
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