title: Experiment on the feasibility of using modified gelatin nanoparticles as insulin pulmonary administration system for diabetes therapy.
abstract: Polymeric nanoparticles are widely used as targeted carriers for biomacromolecules. In this paper, modified gelatin nanoparticles were prepared and their feasibility as insulin pulmonary administration system was investigated. D: ,L: -glyceraldehyde and poloxamer 188 were used for gelatin nanoparticle preparation. Novel water-in-water emulsion technique was used to prepare insulin-loaded nanoparticles. Morphological examination of insulin-loaded nanoparticles was carried out using scanning electron microscopy (SEM). Intratracheal instillation of insulin-loaded nanoparticles was performed to evaluate animal hypoglycemic effect. With fluorescence labeling of insulin, alveolar deposition and absorption of insulin-loaded nanoparticles were investigated. Histological changes in the lung were also observed to evaluate the safety. From the micromorphology observation, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 showed smooth and uniform surface, with average particle size 250 nm and Zeta potential -21.1 mV. From animal experiment, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 promoted insulin pulmonary absorption effectively and showed good relative pharmacological bioavailability. Proved by alveolar deposition result, FITC-insulin-loaded nanoparticle group was characterized by an acute and rapid hypoglycemic effect. In addition, nanoparticles could guarantee the safety of lung by reducing insulin deposition in lung. A transient weak inflammatory response was observed at 1 day after administration. With good physical characterization, high bioavailability, fast and stable hypoglycemic effect, insulin-loaded nanoparticles might be developed as a novel insulin pulmonary system for diabetes therapy.
authors: Wenzhou Medical College, Zhejiang Province, 325035, China.
authors: Ying-Zheng
authors: YZ
authors: Zhao
authors: Xing
authors: X
authors: Li
authors: Cui-Tao
authors: CT
authors: Lu
authors: Yan-Yan
authors: YY
authors: Xu
authors: Hai-Feng
authors: HF
authors: Lv
authors: Dan-Dan
authors: DD
authors: Dai
authors: Lu
authors: L
authors: Zhang
authors: Chang-Zheng
authors: CZ
authors: Sun
authors: Wei
authors: W
authors: Yang
authors: Xiao-Kun
authors: XK
authors: Li
authors: Ya-Ping
authors: YP
authors: Zhao
authors: Hong-Xing
authors: HX
authors: Fu
authors: Lu
authors: L
authors: Cai
authors: Min
authors: M
authors: Lin
authors: Li-Juan
authors: LJ
authors: Chen
authors: Ming
authors: M
authors: Zhang
mesh_terms: D000042:Absorption; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D016503:Drug Delivery Systems / Q000009:adverse effects; D004655:Emulsions; D005240:Feasibility Studies; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000032:analysis; D005780:Gelatin; D005985:Glyceraldehyde; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics; D008168:Lung / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D020442:Poloxamer; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D004655:Emulsions; D007004:Hypoglycemic Agents; D007328:Insulin; C031573:insulin, fluorescein-isothiocyanated-; D020442:Poloxamer; D005985:Glyceraldehyde; D005780:Gelatin; D016650:Fluorescein-5-isothiocyanate