title: Preparation and characterization of gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds.
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.
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Liu
authors.affiliation: Department of Occupational Therapy, I-Shou University, Kaohsiung 824, Taiwan ; Department of Pharmacy, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chang
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan.
authors.forename: Kai-Jen
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Department of Urology, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan.
authors.forename: Tsan-Jung
authors.initials: TJ
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.
authors.forename: Ching-Chung
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.
authors.forename: Hao-Kuang
authors.initials: HK
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Tong-Rong
authors.initials: TR
authors.lastname: Tsai
mesh_terms: D000818:Animals; D005780:Gelatin / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D005976:Glutaral / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D016086:Lentivirus / Q000737:chemistry / Q000235:genetics; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D019459:Urothelium / Q000254:growth & development / Q000503:physiopathology
chemical_list: D020100:Hydrogels; D005780:Gelatin; D005976:Glutaral