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BioMed Research International
Volume 2014, Article ID 473823, 12 pages
http://dx.doi.org/10.1155/2014/473823
Research Article

Preparation and Characterization of Gelatin-Based Mucoadhesive Nanocomposites as Intravesical Gene Delivery Scaffolds

1School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2Department of Occupational Therapy, I-Shou University, Kaohsiung 824, Taiwan
3Department of Pharmacy, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan
4Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan
5Department of Urology, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan
6Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan
7Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan

Received 20 July 2014; Revised 27 September 2014; Accepted 28 September 2014; Published 15 December 2014

Academic Editor: Changyang Gong

Copyright © 2014 Ching-Wen Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H), composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV) release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds.