Gelatin nanoparticle-mediated intranasal delivery of substance P protects against 6-hydroxydopamine-induced apoptosis: an in vitro and in vivo study

• Published in: Drug design, development and therapy Vol. 9; no. default; pp. 1955 - 1962
• Main Authors: Lu, Cui-Tao, Jin, Rong-Rong, Jiang, Yi-Na, Lin, Qian, Yu, Wen-Ze, Mao, Kai-Li, Tian, Fu-Rong, Zhao, Ya-Ping, Zhao, Ying-Zheng
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2015; Taylor & Francis Ltd; Dove Medical Press
• Subjects: 6-Hydroxydopamine; Administration, Intranasal; Animals; Apoptosis; Apoptosis - drug effects; Bioavailability; Brain; Brain diseases; Brain research; Care and treatment; Caspase; Caspase 3 - analysis; Caspase 3 - metabolism; Caspase-3; Cell viability; Cells, Cultured; Disease Models, Animal; Dopamine; Drug Delivery Systems; Gelatin; Gelatin - chemistry; Health aspects; In vivo methods and tests; Inhaled medication; Innovations; Kinases; Laboratory animals; Lipids; Male; Medical research; Molecular Structure; Nanoparticles; Nanoparticles - chemistry; Nervous system; Original Research; Oxidopamine - administration & dosage; Oxidopamine - antagonists & inhibitors; Oxidopamine - pharmacology; Parkinson's disease; PC12 Cells; Rats; Rats, Sprague-Dawley; Rodents; Rotational behavior; Stability analysis; Staining; Structure-Activity Relationship; Substance P; Substance P - administration & dosage; Substance P - chemistry; Substance P - pharmacology; Substantia nigra; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - pathology; China; intranasal delivery; apoptosis; 6-hydroxydopamine; gelatin nanoparticles; substance P; Parkinson’s disease
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S77237

The aim of this study was to investigate the protective role of intranasally administered substance P-loaded gelatin nanoparticles (SP-GNPs) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in vitro and in vivo, and to provide a new strategy for treating brain pathology, such as Parkinson's disease. SP-GNPs were prepared by a water-in-water emulsion method, and their stability, encapsulating efficiency, and loading capacity were evaluated. PC-12 cells were used to examine the enhancement of growth and inhibition of apoptosis by SP-GNPs in vitro using MTT assays. In the in vivo study, hemiparkinsonian rats were created by intracerebroventricular injection of 6-OHDA. The rats then received intranasal SP-GNPs daily for 2 weeks. Functional improvement was assessed by quantifying rotational behavior, and the degree of apoptosis was assessed by immunohistochemical staining for caspase-3 in the substantia nigra region. PC-12 cells with 6-OHDA-induced disease treated with SP-GNPs showed higher cell viability than their untreated counterparts, and cell viability increased as the concentration of substance P (SP) increased, indicating that SP could enhance cell growth and inhibit the cell apoptosis induced by 6-OHDA. Rats with 6-OHDA-induced hemiparkinsonism treated with SP-GNPs made fewer rotations and showed less staining for caspase-3 than their counterparts not treated with SP, indicating that SP protects rats with 6-OHDA-induced hemiparkinsonism from apoptosis and therefore demonstrates their functional improvement. Intranasal delivery of SP-GNPs protects against 6-OHDA-induced apoptosis both in vitro and in vivo.