TY - JOUR
T1 - Cationic biopolymer functionalized nanoparticles encapsulating lutein to attenuate oxidative stress in effective treatment of Alzheimer's disease
T2 - A non-invasive approach
AU - Dhas, Namdev
AU - Mehta, Tejal
N1 - Funding Information:
Authors would like to thank Council of Scientific and Industrial Research (CSIR) and Institute of Pharmacy, Nirma University for providing financial assistance in the form of CSIR-SRF ( 09/1048(007)/2018-EMR-I ) and Nirma University ( NU/IP/stipend/Ph.D./2016 ) to Namdev Dhas. The authors are again thankful to Institute of Pharmacy, Nirma University for providing the necessary facilities to carry out the research work.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/8/30
Y1 - 2020/8/30
N2 - Present investigation explores cationic biopolymer core/shell nanoparticles (Chitosan@PLGA C/SNPs) for delivering carotenoids to brain via intranasal route for supressing oxidative stress in Alzheimer's disease (AD). The prepared C/SNPs exhibited particle size less than 150 nm with more than 80% of entrapment efficiency. Surface morphology confirmed uniform coating of shell (chitosan) over core PLGA NPs and suggested spherical nature and homogenous dispersion of C/SNPs. In-vitro release study demonstrated sustained release of lutein while C/SNPs permeation enhancement was confirmed by ex-vivo diffusion study. The study also investigated effect of cationic-shell with respect to anionic-core NPs on biocompatibility, cellular uptake, uptake mechanism, reactive-oxygen species (ROS) generation, ROS scavenging activity, blood–brain-barrier (BBB) permeation. The cellular uptake revealed enhanced internalization of nanoparticles via caveolae-mediated endocytosis. In-vitro co-culture model of BBB demonstrated efficient passage for C/SNPs through BBB. Antioxidant assay demonstrated significant ROS scavenging activity of C/SNPs. In-vivo pharmacokinetic and bio-distribution was performed along with in-vivo toxicity and stability. In-vivo toxicity demonstrated absence of any significant toxicity. Photo and thermal stability confirmed protection of lutein by C/SNPs. C/SNPs were highly deposited in brain following intranasal route. The obtained results demonstrate the potential application of cationic C/SNPs for attenuating oxidative stress in brain for effective AD therapy.
AB - Present investigation explores cationic biopolymer core/shell nanoparticles (Chitosan@PLGA C/SNPs) for delivering carotenoids to brain via intranasal route for supressing oxidative stress in Alzheimer's disease (AD). The prepared C/SNPs exhibited particle size less than 150 nm with more than 80% of entrapment efficiency. Surface morphology confirmed uniform coating of shell (chitosan) over core PLGA NPs and suggested spherical nature and homogenous dispersion of C/SNPs. In-vitro release study demonstrated sustained release of lutein while C/SNPs permeation enhancement was confirmed by ex-vivo diffusion study. The study also investigated effect of cationic-shell with respect to anionic-core NPs on biocompatibility, cellular uptake, uptake mechanism, reactive-oxygen species (ROS) generation, ROS scavenging activity, blood–brain-barrier (BBB) permeation. The cellular uptake revealed enhanced internalization of nanoparticles via caveolae-mediated endocytosis. In-vitro co-culture model of BBB demonstrated efficient passage for C/SNPs through BBB. Antioxidant assay demonstrated significant ROS scavenging activity of C/SNPs. In-vivo pharmacokinetic and bio-distribution was performed along with in-vivo toxicity and stability. In-vivo toxicity demonstrated absence of any significant toxicity. Photo and thermal stability confirmed protection of lutein by C/SNPs. C/SNPs were highly deposited in brain following intranasal route. The obtained results demonstrate the potential application of cationic C/SNPs for attenuating oxidative stress in brain for effective AD therapy.
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U2 - 10.1016/j.ijpharm.2020.119553
DO - 10.1016/j.ijpharm.2020.119553
M3 - Article
C2 - 32561306
AN - SCOPUS:85086772959
VL - 586
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 119553
ER -