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Exploration of Nanonutraceuticals in Neurodegenerative Diseases
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Nutraceuticals and Dietary Supplements, 2020
Swati Pund, Amita Joshi, Vandana Patravale
Lipophilic molecules cross BBB via transcelluar route while the proteins, peptides, and polysaccharides cross BBB via receptor-mediated transcytosis and through paracellular route. Remarkably receptor-mediated transcytosis, predominantly bi-directional, is also involved in the transportation of nanoparticles as well as biopharmaceuticals (De Boer and Gaillard, 2007). On the other hand, efflux transporters, namely, ABC transporter family, multidrug resistance proteins and brain multidrug resistance proteins, regulate the homeostasis of excitatory transmitters, like glutamate and entry of drugs to the brain. This in turn becomes a major limitation for the drug delivery to the brain for treating central nervous system (CNS) aliments (Löscher and Potschka, 2005). CNS albumin levels are controlled by adsorptive transcytosis depending upon the disease condition (Joó, 1996). Thus, a strong cohesive endothelial system protects the brain allowing a selective access to certain requisite molecules only.
Fundamentals in nasal drug delivery
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Zachary Warnken, Yu Jin Kim, Heidi M. Mansour, Robert O. Williams, Hugh D.C. Smyth
The nasal route of delivery is favorable for the treatment of local symptoms of diseases such as allergy rhinitis and nasal congestion. In addition, nasal drug administration has several demonstrated and potential advantages for the treatment of local, systemic, and central nervous system (CNS) diseases as well. Systemic drug delivery of small molecules, peptides, and proteins has been achieved by noninvasive measures using nasal drug delivery. In addition, the innervation of the nasal cavity provides pathways that can promote drug delivery to the brain, potentially circumventing the blood-brain barrier (BBB) in specific cases. As with any route of delivery, the advantages of the administration method meet with particular challenges associated with the route of delivery. This chapter overviews the fundamentals to delivering drugs by the nasal route of administration, and includes discussion of the barriers to nasal drug delivery as well as the formulation and device technologies that have been invented in order to overcome these barriers.
Administration of Substances and Sampling
Published in Yanlin Wang-Fischer, Manual of Stroke Models in Rats, 2008
Wang-Fischer Yanlin, McCool John
Dr. Frey’s group10 compared intranasal administration of drug on anesthetized mice and unanesthetized mice. They found that intranasal administration of drug on anesthetized mice had better drug delivery to the brain. We abstracted some of their data and summarize it in Table 23.5 (courtesy of Dr. Frey’s group).
Surface-tailoring of emulsomes for boosting brain delivery of vinpocetine via intranasal route: in vitro optimization and in vivo pharmacokinetic assessment
Published in Drug Delivery, 2022
Hibah M. Aldawsari, Shaimaa M. Badr-Eldin, Nourah Y. Assiri, Nabil A. Alhakamy, Anna Privitera, Filippo Caraci, Giuseppe Caruso
Central nervous system (CNS) disorders represent a major public health challenge (Thakur et al., 2016; Caruso et al., 2022). As per World Health Organization (WHO) statistics (www.who.int; accessed on May 24), over than 1 billion people are diagnosed for neurological disorders worldwide. The blood–brain barrier (BBB) permeability and specificity represent crucial challenges for drug delivery to the brain in safe and adequate manner (Liu & Jiang, 2022). The physiological and histological structure of the BBB could be regarded as the main factor accounting for its limited permeability (Fresta et al., 2020). The tight junctions part of the cerebral capillary endothelium along with the transporters play a key role in restricting the delivery of drugs to the CNS (Zidan & Aldawsari, 2015; Vieira & Gamarra, 2016).
Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects
Published in Drug Delivery, 2022
Saleha Rehman, Bushra Nabi, Amaan Javed, Tahira Khan, Ashif Iqubal, Mohammad Javed Ansari, Sanjula Baboota, Javed Ali
Although PPD holds clinical importance in the management of schizophrenia, limitations include poor aqueous solubility (0.03 mg/mL), poor bioavailability (28%), and drug evasion by P-glycoprotein (P-gp) transporters, and poor permeability dissuade it from traversing the blood-brain barrier (BBB). They are the chief reasons for its substandard therapeutic efficacy following oral administration (Rehman et al., 2021). Since schizophrenia is a dreadful neuropsychiatric disorder that warrants treatment adherence, new strategies and approaches are needed to optimize the existing therapies and reduce the associated side effects. Amongst these novel approaches, nanotechnology has been widely investigated for its potential benefits in improving drug delivery to the brain (Radaic & Martins-de-Souza, 2020).
New insight into brain disease therapy: nanomedicines-crossing blood–brain barrier and extracellular space for drug delivery
Published in Expert Opinion on Drug Delivery, 2022
Ziqi Gu, Haishu Chen, Han Zhao, Wanting Yang, Yilan Song, Xiang Li, Yang Wang, Dan Du, Haikang Liao, Wenhao Pan, Xi Li, Yajuan Gao, Hongbin Han, Zhiqian Tong
The development of effective strategies for enhancing drug delivery to the brain has become a topic of great interest in both the clinical and pharmaceutical fields. They have some potential advantages than the traditional drugs. 1) Nanomedicines can pass through BBB and achieve target drug delivery to the desired brain regions. For example, PEG-modified liposomes can pass through BBB and bind to Aβ specifically to diagnose and treat AD [154]. 2) Nanomedicines increase the accumulation of the drug concentrations in the brain by 75% when compared with traditional drug aqueous solution [197]. 3) Nanomedicines can ensure the integrity and biological activity of bioactive substances by avoiding enzyme degradation prematurely, thus improving the stability and bioavailability of drugs. 4) Nanomedicines can reduce the ineffective interaction between drugs and the body, and extend the circulation time of drugs in vivo [198]. 5) Invasive delivering 30 ~ 50 nm nanomedicines via ECS may contribute to the treatment of brain disease. For example, 30 nm coenzyme Q10 (less than the diameter of ECS, 38 ~ 64 nm) shows better curative effects in AD model mice than non-nanoscale-packaged drugs [190].