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Gelatin nanoparticle-mediated intranasal delivery of substance P protects against 6-hydroxydopamine-induced apoptosis: an in vitro and in vivo study.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2015 Apr 07; Vol. 9, pp. 1955-62. Date of Electronic Publication: 2015 Apr 07 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Background: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusion: Intranasal delivery of SP-GNPs protects against 6-OHDA-induced apoptosis both in vitro and in vivo.
- Subjects :
- Administration, Intranasal
Animals
Caspase 3 analysis
Caspase 3 metabolism
Cells, Cultured
Disease Models, Animal
Male
Molecular Structure
Oxidopamine administration & dosage
Oxidopamine pharmacology
PC12 Cells
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Substance P chemistry
Substantia Nigra drug effects
Substantia Nigra metabolism
Substantia Nigra pathology
Apoptosis drug effects
Drug Delivery Systems
Gelatin chemistry
Nanoparticles chemistry
Oxidopamine antagonists & inhibitors
Substance P administration & dosage
Substance P pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 25897205
- Full Text :
- https://doi.org/10.2147/DDDT.S77237