title: Injectable Chitosan/β-Glycerophosphate System for Sustained Release: Gelation Study, Structural Investigation, and Erosion Tests.
abstract: Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the "optimized composition", namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Dalmoro
authors.forename: Michela
authors.initials: M
authors.lastname: Abrami
authors.forename: Barbara
authors.initials: B
authors.lastname: Galzerano
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bochicchio
authors.forename: Anna Angela
authors.initials: AA
authors.lastname: Barba
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.affiliation: Istituto per i Polimeri i Compositi ed i Biomateriali - Consiglio Nazionale delle Ricerche - P.le E. Fermi 1, 80055 Portici, Naples, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Larobina
mesh_terms: D019342:Acetic Acid / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D065546:Drug Liberation; D005994:Glycerophosphates / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D007267:Injections; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012212:Rheology; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D005994:Glycerophosphates; D020100:Hydrogels; D048271:Chitosan; D019342:Acetic Acid; C031463:beta-glycerophosphoric acid
keywords: Chitosan; erosion; hydrogel; mesh-size; thermo-gelling; β-glycerophosphate