Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer&amp;rsquo;s disease

Meng, Qingqing; Wang, Aiping; Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei; Sun, Kaoxiang

doi:10.2147/ijn.s151474

Cited by 230 publications

(109 citation statements)

References 44 publications

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“…Another study developed huperzine A-loaded, mucoadhesive, and targeted PLGA nanoparticles with surface modification by lactoferrin-conjugated N-trimethylated chitosan for efficient intranasal delivery of huperzine A to the brain for AD treatment. These nanoparticles showed good sustained-release effect, adhesion, targeting ability, and a broad application prospect as a nasal drug delivery carrier [207]. These studies suggest that particle transport via the nose-to-brain route is highly affected by the particle surface chemistry.…”

Section: Nanoparticles Composed Of Chitosan and Chitosan Derivativesmentioning

confidence: 83%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices. Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neurodegenerative disease, leading to the development of bradykinesia and tremors of cardinal motor functions ( Figure 2) [3]. PD models specifically show a decrease in dopamine transporters, which are responsible for dopamine uptake by dopaminergic neurons and progression of neuronal communications. Reduced Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neuro...

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Section: Nanoparticles Composed Of Chitosan and Chitosan Derivativesmentioning

confidence: 83%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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“…Non-invasive administration routes remain preferable in humans and among them, although bearing some limitations, oral management represents a safe and practical approach for Lf supplementation. Beside oral administration [48], several different other modes have been tested in animal models and humans, including aerosolized [45,46], intranasal [52], sublingual [53], intravenous [54], intraperitoneal [55], and intravaginal administration [56].…”

Section: Lactoferrin Bioavailability: Absorption and Body Deliverymentioning

confidence: 99%

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radioand chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies.

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“…Furthermore, cellular uptake experiments demonstrated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in SH-SY5Y and 16HBE cells. HupA-PLGA-NPs improved the bioavailability and targeting ability of the drug (Meng et al, 2018). In AD rat model, berberine (BRB)-loaded multiwalled carbon nanotubes (MWCNTs) coated with phospholipid and polysorbate, remanded the memory impairment and reduced the β-amyloid induced-AD compared with its free form (Lohan et al, 2017).…”

Section: Plant-mediated Nano Systemsmentioning

confidence: 99%

Nanoformulations of Herbal Extracts in Treatment of Neurodegenerative Disorders

Moradi

Momtaz

Bayrami

et al. 2020

Front. Bioeng. Biotechnol.

113

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Nanotechnology is one of the methods that influenced human life in different ways and is a substantial approach that assists to overcome the multiple limitations of various diseases, particularly neurodegenerative disorders (NDs). Diverse nanostructures such as polymer nanoparticles, lipid nanoparticles, nanoliposomes, nano-micelles, and carbon nanotubes (CNTs); as well as different vehicle systems including poly lacticco-glycolic acid, lactoferrin, and polybutylcyanoacrylate could significantly increase the effectiveness, reduce the side effects, enhance the stability, and improve the pharmacokinetics of many drugs. NDs belong to a group of annoying and debilitating diseases that involve millions of people worldwide. Previous studies revealed that several nanoformulations from a number of natural products such as curcumin (Cur), quercetin (QC), resveratrol (RSV), piperine (PIP), Ginkgo biloba, and Nigella sativa significantly improved the condition of patients diagnosed with NDs. Drug delivery to the central nervous system (CNS) has several limitations, in which the blood brain barrier (BBB) is the main drawback for treatment of NDs. This review discusses the effects of herbalbased nanoformulations, their advantages and disadvantages, to manage NDs. In summary, we conclude that herbal-based nano systems have promising proficiency in treatment of NDs, either alone or in combination with other drugs.

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Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

Cited by 230 publications

References 44 publications

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

Nanoformulations of Herbal Extracts in Treatment of Neurodegenerative Disorders

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