Non-Invasive Intranasal Delivery of pApoE2: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain

Gothwal, Avinash; Lamptey, Richard Nii Lante; Trivedi, Riddhi; Chaulagain, Bivek; Singh, Jagdish

doi:10.3390/ijms241613019

Cited by 2 publications

(2 citation statements)

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“…The in vitro findings showed higher transfection of pApoE2 in primary astrocytes and primary neurons by dual-functionalized micelles. The in vivo results were also in the notion of in vitro findings, multifunctionalized polymeric micelles-treated mice showed higher ApoE2 expression in the brain over un-functionalized polymeric micelles (Gothwal et al, 2023b).…”

Section: Functionalized Polymeric Micelles For Nucleic Acid Delivery ...mentioning

confidence: 68%

“…Multi-functionalized PEN tagged with chitosan polymeric micelles have shown higher in vitro transfection without causing any significant toxicity (Layek and Singh, 2013). Higher gene transfection was also achieved in the brain when multifunctionalized chitosan polymeric micelles were tagged with PEN (Gothwal et al, 2023a;Gothwal et al, 2023b). Similarly, Angiopep CPP was explored with PEG-PCL polymeric micelles for effective drug delivery across the BBB (Xin et al, 2011).…”

Section: Functionalization Strategies Used In Polymeric Micellesmentioning

confidence: 99%

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Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease

Muolokwu,

Chaulagain,

Gothwal

et al. 2024

Front. Pharmacol.

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Brain-targeted gene delivery across the blood-brain barrier (BBB) is a significant challenge in the 21st century for the healthcare sector, particularly in developing an effective treatment strategy against Alzheimer’s disease (AD). The Internal architecture of the brain capillary endothelium restricts bio-actives entry into the brain. Additionally, therapy with nucleic acids faces challenges like vulnerability to degradation by nucleases and potential immune responses. Functionalized nanocarrier-based gene delivery approaches have resulted in safe and effective platforms. These nanoparticles (NPs) have demonstrated efficacy in protecting nucleic acids from degradation, enhancing transport across the BBB, increasing bioavailability, prolonging circulation time, and regulating gene expression of key proteins involved in AD pathology. We provided a detailed review of several nanocarriers and targeting ligands such as cell-penetrating peptides (CPPs), endogenous proteins, and antibodies. The utilization of functionalized NPs extends beyond a singular system, serving as a versatile platform for customization in related neurodegenerative diseases. Only a few numbers of bioactive regimens can go through the BBB. Thus, exploring functionalized NPs for brain-targeted gene delivery is of utmost necessity. Currently, genes are considered high therapeutic potential molecules for altering any disease-causing gene. Through surface modification, nanoparticulate systems can be tailored to address various diseases by replacing the target-specific molecule on their surface. This review article presents several nanoparticulate delivery systems, such as lipid NPs, polymeric micelles, exosomes, and polymeric NPs, for nucleic acids delivery to the brain and the functionalization strategies explored in AD research.

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Section: Functionalized Polymeric Micelles For Nucleic Acid Delivery ...mentioning

confidence: 68%

Section: Functionalization Strategies Used In Polymeric Micellesmentioning

confidence: 99%

Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease

Muolokwu,

Chaulagain,

Gothwal

et al. 2024

Front. Pharmacol.

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Mannose-Functionalized Chitosan-Coated PLGA Nanoparticles for Brain-Targeted Codelivery of CBD and BDNF for the Treatment of Alzheimer’s Disease

Mahanta,

Chaulagain,

Trivedi

et al. 2024

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is a common neurodegenerative disease causing cognitive and memory decline. AD is characterized by the deposition of amyloid-β and hypophosphorylated forms of tau protein. AD brains are found to be associated with neurodegeneration, oxidative stress, and inflammation. Cannabidiol (CBD) shows neuroprotective, antioxidant, and antiinflammatory properties and simultaneously reduces amyloid-β production and tau hyperphosphorylation. The brain-derived neurotrophic factor (BDNF) plays a vital role in the development and maintenance of the plasticity of the central nervous system. A decline of BDNF levels in AD patients results in reduced plasticity and neuronal cell death. Current therapeutics against AD are limited to only symptomatic relief, necessitating a therapeutic strategy that reverses cognitive decline. In this scenario, combination therapy of CBD and BDNF could be a fruitful strategy for the treatment of AD. We designed mannose-conjugated chitosan-coated poly(D,L-lactide-co-glycolide (PLGA) (CHTMAN-PLGA) nanoparticles for the codelivery of CBD and BDNF to the brain. Chitosan is modified with mannose to specifically target the glucose transporter-1 (GLUT-1) receptor abundantly present in the blood−brain barrier for selectively delivering therapeutics to the brain. The CBD-encapsulated nanoparticles showed an average hydrodynamic diameter of 306 ± 8.12 nm and a zeta potential of 31.7 ± 1.53 mV. The coated nanoparticles prolonged encapsulated CBD release from the PLGA matrix. The coated nanoparticles exhibited sustained release of CBD for up to 22 days with 91.68 ± 2.91% release of the encapsulated drug. The coated nanoparticles, which had a high positive zeta potential (31.7 ± 1.53 mV), encapsulated the plasmid DNA. The qualitative transfection efficiency was investigated using CHTMAN-PLGA-CBD/pGFP in bEND.3, primary astrocytes, and primary neurons, while the quantitative transfection efficiency of the delivery system was determined using CHTMAN-PLGA-CBD/pBDNF. In vitro, the pBDNF transfection study revealed that the BDNF expression was 4-fold higher for CHTMAN-PLGA-CBD/pBDNF than for naked pBDNF in all of the cell lines. The cytotoxicity and hemocompatibility of the designed nanoparticles were tested in bEND.3 cells and red blood cells, respectively, and the nanoparticles were found to be nontoxic and hemocompatible. Hence, mannose-conjugated chitosan-coated PLGA nanoparticles could be useful as brain-targeting delivery vehicles for the codelivery of CBD and BDNF for possible AD treatment.

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Non-Invasive Intranasal Delivery of pApoE2: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain

Cited by 2 publications

References 46 publications

Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease

Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease

Mannose-Functionalized Chitosan-Coated PLGA Nanoparticles for Brain-Targeted Codelivery of CBD and BDNF for the Treatment of Alzheimer’s Disease

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