title: Gelatin nanoparticle-mediated intranasal delivery of substance P protects against 6-hydroxydopamine-induced apoptosis: an in vitro and in vivo study.
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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Intranasal delivery of SP-GNPs protects against 6-OHDA-induced apoptosis both in vitro and in vivo.
authors.affiliation: The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China ; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Cui-Tao
authors.initials: CT
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Yi-Na
authors.initials: YN
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Wen-Ze
authors.initials: WZ
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Mao
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Tian
authors.affiliation: The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005780:Gelatin / Q000737:chemistry*; D008297:Male; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D016627:Oxidopamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013373:Substance P / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D013373:Substance P; D016627:Oxidopamine; D005780:Gelatin; D053148:Caspase 3
keywords: 6-hydroxydopamine; Parkinson’s disease; apoptosis; gelatin nanoparticles; intranasal delivery; substance P