Preparation and characterisation of PHT-loaded chitosan lecithin nanoparticles for intranasal drug delivery to the brain

Yousfan, Amal; Rubio, Noelia; Natouf, Abdul Hakim; Daher, Aamal; Al-Kafry, Nedal; Venner, Kerrie; Kafa, Houmam

doi:10.1039/d0ra04890a

Cited by 30 publications

(21 citation statements)

References 54 publications

(80 reference statements)

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“…Nanoparticles were present in the nasal cavity for up to 24 h, allowing additional time for them to reach the brain [149]. Similarly, chitosan-lecithin NPs for brain targeting loaded with phenytoin demonstrated relatively high accumulation in brain and low phenytoin levels in plasma after intranasal delivery as compared to intraperitoneal injection, which produced initial high plasma levels before crossing the blood-brain barrier [150]. The intraocular delivery of chitosan inserts radiolabeled with Tc-99m resulted in the retention of NPs for up to 6-8 h at the site of instillation in the eye, after which the formulation accumulated in the gastrointestinal tract, mainly the large intestine, via nasolacrimal clearance [151,152].…”

Section: Effect Of Mucosal Routes Of Administrationmentioning

confidence: 99%

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

et al. 2021

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The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems. We aim to analyze recent research studying interactions of chitosan nanoparticles (NPs) upon their cellular uptake and their journey through the various compartments of the cell. The positive charge of chitosan enables it to efficiently attach to cells, increasing the probability of cellular uptake. Chitosan NPs are taken up by cells via different pathways and escape endosomal degradation due to the proton sponge effect. Furthermore, we have reviewed the interaction of chitosan NPs upon in vivo administration. Chitosan NPs are immediately surrounded by a serum protein corona in systemic circulation upon intravenous administration, and their biodistribution is mainly to the liver and spleen indicating RES uptake. However, the evasion of RES system as well as the targeting ability and bioavailability of chitosan NPs can be improved by utilizing specific routes of administration and covalent modifications of surface properties. Ongoing clinical trials of chitosan formulations for therapeutic applications are paving the way for the introduction of chitosan into the pharmaceutical market and for their toxicological evaluation. Chitosan provides specific biophysical properties for effective and tunable cellular uptake and systemic delivery for a wide range of applications.

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Section: Effect Of Mucosal Routes Of Administrationmentioning

confidence: 99%

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

et al. 2021

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“…In another recent study, chitosan–lecithin nanoparticles loaded with the anti-seizure medication phenytoin were intranasally administered in conscious mice [ 24 ]. The drug delivery of phenytoin is particularly challenging due to the drug’s low aqueous solubility and tendency to crystallize, causing slow absorption and post-injection pain.…”

Section: Methods To Combat Structural Chemical and Transport-mediated Challenges Of Drug Delivery Across The Bbbmentioning

confidence: 99%

“…Additionally, phenytoin is both highly protein-bound and classified as a Pgp substrate, resulting in low brain bioavailability. However, the study found that the intranasal administration of phenytoin-loaded chitosan–lecithin nanoparticles in BALBc mice resulted in a rapid accumulation of phenytoin in the mouse brain after 5 and 60 min, along with sustained concentrations 72 h after administration [ 24 ].…”

Section: Methods To Combat Structural Chemical and Transport-mediated Challenges Of Drug Delivery Across The Bbbmentioning

confidence: 99%

Drug Delivery Challenges in Brain Disorders across the Blood–Brain Barrier: Novel Methods and Future Considerations for Improved Therapy

2021

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Due to the physiological and structural properties of the blood–brain barrier (BBB), the delivery of drugs to the brain poses a unique challenge in patients with central nervous system (CNS) disorders. Several strategies have been investigated to circumvent the barrier for CNS therapeutics such as in epilepsy, stroke, brain cancer and traumatic brain injury. In this review, we summarize current and novel routes of drug interventions, discuss pharmacokinetics and pharmacodynamics at the neurovascular interface, and propose additional factors that may influence drug delivery. At present, both technological and mechanistic tools are devised to assist in overcoming the BBB for more efficient and improved drug bioavailability in the treatment of clinically devastating brain disorders.

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“…Nasal drug delivery is a non-intrusive technique of delivering drugs to the respiratory system, the central nervous system (CNS), and/or systemic circulation [ 189 ]. Intranasal delivery offers direct to brain drug delivery via intracellular and extracellular pathways, involving transcellular, paracellular, and extracellular transport mechanisms alongside the olfactory and trigeminal nerve fibers [ 190 ].…”

Section: Opportunities For Cross-linked Gels In Cns Drug Deliverymentioning

confidence: 99%

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders

Mashabela

Maboa

Miya

et al. 2022

Gels

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Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.

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Preparation and characterisation of PHT-loaded chitosan lecithin nanoparticles for intranasal drug delivery to the brain

Abstract: The use of nanoparticles (NPs) for intranasal (IN) drug delivery to the brain represents a hopeful strategy to enhance brain targeting of anti-epileptic drugs.

Cited by 30 publications

References 54 publications

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

Drug Delivery Challenges in Brain Disorders across the Blood–Brain Barrier: Novel Methods and Future Considerations for Improved Therapy

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders

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