A scalable controlled-release device for transscleral drug delivery to the retina

被引:33
|
作者
Kawashima, Takeaki [2 ]
Nagai, Nobuhiro [1 ]
Kaji, Hirokazu [2 ,3 ]
Kumasaka, Norihiro [1 ]
Onami, Hideyuki [4 ]
Ishikawa, Yumi [1 ]
Osumi, Noriko [5 ]
Nishizawa, Matsuhiko [2 ,3 ]
Abe, Toshiaki [1 ]
机构
[1] Tohoku Univ, Grad Sch Med, Ctr Adv Med Res & Dev, Div Clin Cell Therapy,ART,Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Tohoku Univ, Grad Sch Engn, Dept Bioengn & Robot, Aoba Ku, Sendai, Miyagi 9808579, Japan
[3] CREST, JST, Chiyoda Ku, Tokyo 1020075, Japan
[4] Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Aoba Ku, Sendai, Miyagi 9808574, Japan
[5] Tohoku Univ, Grad Sch Med, Ctr Neurosci, Div Dev Neurosci,ART,Aobu Ku, Sendai, Miyagi 9808575, Japan
基金
日本科学技术振兴机构;
关键词
Drug-delivery system; Transscleral delivery; Controlled release; Retinal neuroprotection; Polyethylene glycol; NEUROTROPHIC FACTOR; SUSTAINED-RELEASE; GANGLION-CELLS; PHOTORECEPTOR DEGENERATION; CYTOMEGALOVIRUS RETINITIS; OPTIC-NERVE; IN-VITRO; GANCICLOVIR; ACETONIDE; SCAFFOLDS;
D O I
10.1016/j.biomaterials.2010.11.006
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
A transscleral drug-delivery device, designed for the administration of protein-type drugs, that consists of a drug reservoir covered with a controlled-release membrane was manufactured and tested. The controlled-release membrane is made of photopolymerized polyethylene glycol dimethacrylate (PEGDM) that contains interconnected collagen microparticles (COLs), which are the routes for drug permeation. The results showed that the release of 40-kDa FITC-dextran (FD40) was dependent on the COL concentration, which indicated that FD40 travelled through the membrane-embedded COLs. Additionally, the sustained-release drug formulations, FD40-loaded COLS and FD40-loaded COLs pelletized with PEGDM, fine-tuned the release of FD40. Capsules filled with COLs that contained recombinant human brain-derived neurotrophic factor (rhBDNF) released bioactive rhBDNF in a manner dependent on the membrane COL concentration, as was found for FD40 release. When capsules were sutured onto sclerae of rabbit eyes, FD40 was found to spread to the retinal pigment epithelium. Implantation of the device was easy, and it did not damage the eye tissues. In conclusion, our capsule is easily modified to accommodate different release rates for protein-type drugs by altering the membrane COL composition and/or drug formulation and can be implanted and removed with minor surgery. The device thus has great potential as a conduit for continuous, controlled drug release. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1950 / 1956
页数:7
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