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Nobuhiro Nagai, Zhaleh Kashkouli Nezhad, Saaya Saijo, Hirokazu Kaji, Matsuhiko Nishizawa, Toru Nakazawa, Toshiaki Abe; Biodegradable injectable sheet as transscleral drug delivery system. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4464.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the in vitro and in vivo drug release of a biodegradable injectable sheet made of cross-linked chitosan and gelatin mixture.
Gelatin and chitosan were solved in water and 1% acetic acid at concentrations of 5 wt% and 2.5 wt%, respectively. Then, 5 wt% gelatin and 2.5 wt% chitosan was mixed at the ratio of 3 : 2 (vol). The drug was mixed with the 3 wt% gelatin/1 wt% chitosan mixture. Fluorescein isothiocyanate (FITC), FITC-labeled dextran 150 kDa (FD150), and FITC-labeled albumin (FITC-ALB) were used as drugs. Immedeately after adding water soluble carbodiimide in the gelatin/chitosan/drug mixture at final concentration of 10 mg/mL, 3 μL of the mixture was cast in the polydimethylsilane (PDMS) mold (internal diameter; 2.76 mm, depth; 0.5 mm). Then, the cross-linked gels were dried for 1 hour at room temperutere to make flexible sheets. The sheets were incubated in phosphate buffered saline (PBS) at 37 degrees C. The drug concentration in PBS were measured spectrofluorometrically. The sheets were placed on the sclerae of rats and cryo-sections of the eyes were observed by fluorescent microscope. HE staining was conducetd to evaluate the biodegradation of the sheets.
Drug release from the sheets was confirmed in vitro for 4 weeks. The sheet can be ejected from 21 G needle with 1 mL syringe. Fluorescence of released FITC, FD150, and FITC-ALB was detected in the sclera, choroid, and retinal pigment epithelium for 2 weeks implantation. The sheets were gradually biodegraded for 2 weeks.
The biodegradable injectable sheet consisted of cross-linked gelatin/chitosan formulation was developed. The sheets could be injected through a conventional syringe needle into water to recover its original shape, and was capable of sustained release of protein type drugs. It therefore provides the possibility of minimally invasive transplantation into episclera space, and could provide better therapeutic outcomes and reduce possible side effects.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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