A scalable controlled-release device for transscleral drug delivery to the retina.
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.
Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, 6-6-01 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan.
Takeaki
T
Kawashima
Nobuhiro
N
Nagai
Hirokazu
H
Kaji
Norihiro
N
Kumasaka
Hideyuki
H
Onami
Yumi
Y
Ishikawa
Noriko
N
Osumi
Matsuhiko
M
Nishizawa
Toshiaki
T
Abe
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D003911:Dextrans / Q000008:administration & dosage / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure
D019208:Brain-Derived Neurotrophic Factor; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D003094:Collagen; D016650:Fluorescein-5-isothiocyanate