TY - JOUR
T1 - Transscleral sustained ranibizumab delivery using an episcleral implantable device
T2 - Suppression of laser-induced choroidal neovascularization in rats
AU - Nagai, Nobuhiro
AU - Nezhad, Zhaleh Kashkouli
AU - Daigaku, Reiko
AU - Saijo, Saaya
AU - Song, Yuanhui
AU - Terata, Keiko
AU - Hoshi, Ayako
AU - Nishizawa, Matsuhiko
AU - Nakazawa, Toru
AU - Kaji, Hirokazu
AU - Abe, Toshiaki
PY - 2019/8/15
Y1 - 2019/8/15
N2 - Successful treatment of age-related macular diseases requires an effective controlled drug release system with less invasive route of administration in the eye to reduce the burden of frequent intravitreal injections for patients. In this study, we developed an episcleral implantable device for sustained release of ranibizumab, and evaluated its efficacy on suppression of laser-induced choroidal neovascularization (CNV) in rats. We tested both biodegradable and non-biodegradable sheet-type devices consisting of crosslinked gelatin/chitosan (Gel/CS) and photopolymerized poly(ethyleneglycol) dimethacrylate that incorporated collagen microparticles (PEGDM/COL). In vitro release studies of FITC-labeled albumin showed a constant release from PEGDM/COL sheets compared to Gel/CS sheets. The Gel/CS sheets gradually biodegraded in the sclera during the 24-week implantation; however, the PEGDM/COL sheets did not degrade. FITC-albumin was detected in the retina during 18 weeks implantation in the PEGDM/COL sheet-treated group, and was detected in the Gel/CS sheet-treated group during 6 weeks implantation. CNV was suppressed 18 weeks after application of ranibizumab-loaded PEGDM/COL sheets compared to a placebo PEGDM/COL sheet-treated group, and to the intravitreal ranibizumab-injected group. In conclusion, the PEGDM/COL sheet device suppressed CNV via a transscleral administration route for 18 weeks, indicating that prolonged sustained ranibizumab release could reduce the burden of repeated intravitreal injections.
AB - Successful treatment of age-related macular diseases requires an effective controlled drug release system with less invasive route of administration in the eye to reduce the burden of frequent intravitreal injections for patients. In this study, we developed an episcleral implantable device for sustained release of ranibizumab, and evaluated its efficacy on suppression of laser-induced choroidal neovascularization (CNV) in rats. We tested both biodegradable and non-biodegradable sheet-type devices consisting of crosslinked gelatin/chitosan (Gel/CS) and photopolymerized poly(ethyleneglycol) dimethacrylate that incorporated collagen microparticles (PEGDM/COL). In vitro release studies of FITC-labeled albumin showed a constant release from PEGDM/COL sheets compared to Gel/CS sheets. The Gel/CS sheets gradually biodegraded in the sclera during the 24-week implantation; however, the PEGDM/COL sheets did not degrade. FITC-albumin was detected in the retina during 18 weeks implantation in the PEGDM/COL sheet-treated group, and was detected in the Gel/CS sheet-treated group during 6 weeks implantation. CNV was suppressed 18 weeks after application of ranibizumab-loaded PEGDM/COL sheets compared to a placebo PEGDM/COL sheet-treated group, and to the intravitreal ranibizumab-injected group. In conclusion, the PEGDM/COL sheet device suppressed CNV via a transscleral administration route for 18 weeks, indicating that prolonged sustained ranibizumab release could reduce the burden of repeated intravitreal injections.
KW - Age-related macular disease
KW - Choroidal neovascularization
KW - Drug delivery system
KW - Polyethylene glycol dimethacrylate
KW - Retina
KW - Transscleral delivery
UR - http://www.scopus.com/inward/record.url?scp=85068177174&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068177174&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.118458
DO - 10.1016/j.ijpharm.2019.118458
M3 - Article
C2 - 31247277
AN - SCOPUS:85068177174
VL - 567
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 118458
ER -