Brain targeting of resveratrol by nasal administration of chitosan-coated lipid microparticles

Trotta, Valentina; Pavan, Barbara; Ferraro, Luca; Beggiato, Sarah; Traini, Daniela; Reis, Larissa Gomes Des; Scalia, Santo; Dalpiaz, Alessandro

doi:10.1016/j.ejpb.2018.02.010

Cited by 75 publications

(50 citation statements)

References 57 publications

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“…For instance, 0.3% (w/v) chitosan significantly increased the brain deposition of zolmitriptan when administered in an oil-in-water emulsion [201]. It has been reported that when resveratrol lipid microparticles were coated with chitosan and administered intranasally as lipid particles at the dose of 60 µm to a rat model, a dramatic and specific 6-fold increase, without any detectable systemic exposure, was observed in its distribution to the cerebrospinal fluid [202]. 7.6.…”

Section: Nanoparticles Composed Of Chitosan and Chitosan Derivativesmentioning

confidence: 99%

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: 99%

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

et al. 2020

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“…A drastic increase was observed in RSV uptake in the cerebrospinal fluid of rats using lipidic particles coated with chitosan (8.75 % v/w) in comparison with uncoated particles and pure RSV. Indeed, the obtained RSV C max after 60 min of nasal administration was 12.2‐fold higher than for uncoated particles while no detectable amounts was noticed from pure RSV …”

Section: Overcoming Limitationsmentioning

confidence: 90%

“…These particles were irregular in shape, with a mean diameter of 85 μm, and presented an encapsulation efficiency of 81 %. The ζ‐potential measurements indicated a high positive value of 45±3 mV which did not show variation after six months of storage at 4 °C, demonstrating a good stability …”

Section: Delivery Systemsmentioning

confidence: 93%

“…The ζ-potential measurements indicated a high positive value of 45 � 3 mV which did not show variation after six months of storage at 4°C, demonstrating a good stability. [40] Similarly, Wu and co-workers prepared RSV-loaded chitosan nanoparticles via anionic cross-linking for chemotherapy. [41] The nanoparticles were made of positively charged chitosan and Poloxamer 188.…”

Section: Lipidic Particlesmentioning

confidence: 99%

“…Indeed, the obtained RSV C max after 60 min of nasal administration was 12.2-fold higher than for uncoated particles while no detectable amounts was noticed from pure RSV. [40] The bioavailability of RSV was also performed using gel nanosuspensions administered via intranasal and intravenous routes. The results showed that the bioavailability in brain was enhanced ca.…”

Section: Bioavailabilitymentioning

confidence: 99%

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Recent Strategies in Resveratrol Delivery Systems

2019

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Resveratrol, a natural polyphenolic stilbenoid widely found in grapes and wines, displays beneficial properties such as cardio‐protective, antioxidant and anti‐inflammatory activities. Trans‐resveratrol (RSV) is the most bioactive and more abundant stereoisomer found in nature. Despite the positive properties of RSV, there are various factors that limit its effectiveness, including low aqueous solubility, low oral bioavailability and chemical instability. During the last years, an increasing number of strategies such as nano and micro encapsulation have been developed in order to overcome these limitations and enhance the use of RSV in nutritional and pharmaceutical applications. This Review summarizes the advances and main properties of several RSV carriers and delivery systems reported during the last 5 years.

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