TY - JOUR
T1 - Nose to brain delivery of rotigotine loaded chitosan nanoparticles in human SH-SY5Y neuroblastoma cells and animal model of Parkinson's disease
AU - Bhattamisra, Subrat K.
AU - Shak, Angeline Tzeyung
AU - Xi, Lim Wen
AU - Safian, Nurul Hasyanazifa
AU - Choudhury, Hira
AU - Lim, Wei Meng
AU - Shahzad, Naiyer
AU - Alhakamy, Nabil A.
AU - Anwer, Md Khalid
AU - Radhakrishnan, Ammu K.
AU - Md, Shadab
N1 - Funding Information:
The authors are thankful to Ministry of Science and Technology Innovation (MOSTI), Kuala Lumpur, Malaysia, grant number ( 02-02-09-SF0055 ), funded this research. The authors are thankful to Brian L. Furman (University of Strathclyde, Glasgow, UK) for his critical reading of the manuscript and English editing.
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/15
Y1 - 2020/4/15
N2 - Rotigotine, a non-ergoline dopamine agonist, has been shown to be highly effective for the treatment of Parkinson's disease (PD). However, despite its therapeutic potential, its’ clinical applications were hindered due to low aqueous solubility, first-pass metabolism and low bioavailability. Therefore, we developed rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery and evaluated its neuronal uptake, antioxidant and neuroprotective effects using cell-based studies. The pharmacological effects of nose-to-brain delivery of the RNPs were also evaluated in an animal model of PD. The average particle size, particle size distribution and entrapment efficiency of the RNPs were found to be satisfactory. Exposure of RNPs for 24 h did not show any cytotoxicity towards SH-SY5Y human neuroblastoma cells. Furthermore, the RNPs caused a decrease in alpha-synuclein (SNCA) and an increase in tyrosine hydroxylase (TH) expression in these cells, suggestion that the exposure alleviated some of the direct neurotoxic effects of 6-OHDA. Behavioral and biochemical testing of RNPs in haloperidol-induced PD rats showed a reversal of catalepsy, akinesia and restoration of swimming ability. A decrease in lactate dehydrogenase (LDH) and an increase in catalase activities were also observed in the brain tissues. The results from the animal model of PD show that intranasally-administered RNPs enhanced brain targeting efficiency and drug bioavailability. Thus, RNPs for nose-to-brain delivery has significant potential to be developed as a treatment approach for PD.
AB - Rotigotine, a non-ergoline dopamine agonist, has been shown to be highly effective for the treatment of Parkinson's disease (PD). However, despite its therapeutic potential, its’ clinical applications were hindered due to low aqueous solubility, first-pass metabolism and low bioavailability. Therefore, we developed rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery and evaluated its neuronal uptake, antioxidant and neuroprotective effects using cell-based studies. The pharmacological effects of nose-to-brain delivery of the RNPs were also evaluated in an animal model of PD. The average particle size, particle size distribution and entrapment efficiency of the RNPs were found to be satisfactory. Exposure of RNPs for 24 h did not show any cytotoxicity towards SH-SY5Y human neuroblastoma cells. Furthermore, the RNPs caused a decrease in alpha-synuclein (SNCA) and an increase in tyrosine hydroxylase (TH) expression in these cells, suggestion that the exposure alleviated some of the direct neurotoxic effects of 6-OHDA. Behavioral and biochemical testing of RNPs in haloperidol-induced PD rats showed a reversal of catalepsy, akinesia and restoration of swimming ability. A decrease in lactate dehydrogenase (LDH) and an increase in catalase activities were also observed in the brain tissues. The results from the animal model of PD show that intranasally-administered RNPs enhanced brain targeting efficiency and drug bioavailability. Thus, RNPs for nose-to-brain delivery has significant potential to be developed as a treatment approach for PD.
KW - Chitosan nanoparticles
KW - Haloperidol
KW - Neuroprotection
KW - Nose to brain delivery
KW - Rotigotine
KW - SH-SY5Y cell uptake
UR - http://www.scopus.com/inward/record.url?scp=85079685338&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2020.119148
DO - 10.1016/j.ijpharm.2020.119148
M3 - Article
C2 - 32084576
AN - SCOPUS:85079685338
SN - 0378-5173
VL - 579
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 119148
ER -
