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      Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease

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      International Journal of Pharmaceutics
      Elsevier BV

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          Intranasal delivery of biologics to the central nervous system.

          Treatment of central nervous system (CNS) diseases is very difficult due to the blood-brain barrier's (BBB) ability to severely restrict entry of all but small, non-polar compounds. Intranasal administration is a non-invasive method of drug delivery which may bypass the BBB to allow therapeutic substances direct access to the CNS. Intranasal delivery of large molecular weight biologics such as proteins, gene vectors, and stem cells is a potentially useful strategy to treat a variety of diseases/disorders of the CNS including stroke, Parkinson's disease, multiple sclerosis, Alzheimer's disease, epilepsy, and psychiatric disorders. Here we give an overview of relevant nasal anatomy and physiology and discuss the pathways and mechanisms likely involved in drug transport from the nasal epithelium to the CNS. Finally we review both pre-clinical and clinical studies involving intranasal delivery of biologics to the CNS. Copyright © 2011 Elsevier B.V. All rights reserved.
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            Evaluation of intranasal delivery route of drug administration for brain targeting

            The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.
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              Intranasal delivery to the central nervous system: mechanisms and experimental considerations.

              The blood-brain barrier (BBB) limits the distribution of systemically administered therapeutics to the central nervous system (CNS), posing a significant challenge to drug development efforts to treat neurological and psychiatric diseases and disorders. Intranasal delivery is a noninvasive and convenient method that rapidly targets therapeutics to the CNS, bypassing the BBB and minimizing systemic exposure. This review focuses on the current understanding of the mechanisms underlying intranasal delivery to the CNS, with a discussion of pathways from the nasal cavity to the CNS involving the olfactory and trigeminal nerves, the vasculature, the cerebrospinal fluid, and the lymphatic system. In addition to the properties of the therapeutic, deposition of the drug formulation within the nasal passages and composition of the formulation can influence the pathway a therapeutic follows into the CNS after intranasal administration. Experimental factors, such as head position, volume, and method of administration, and formulation parameters, such as pH, osmolarity, or inclusion of permeation enhancers or mucoadhesives, can influence formulation deposition within the nasal passages and pathways followed into the CNS. Significant research will be required to develop and improve current intranasal treatments and careful consideration should be given to the factors discussed in this review. 2009 Wiley-Liss, Inc. and the American Pharmacists Association
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                Author and article information

                Journal
                International Journal of Pharmaceutics
                International Journal of Pharmaceutics
                Elsevier BV
                03785173
                September 2021
                September 2021
                : 606
                : 120881
                Article
                10.1016/j.ijpharm.2021.120881
                34273426
                9f42cb3a-980b-47b6-8b38-f8d7424aea7b
                © 2021

                https://www.elsevier.com/tdm/userlicense/1.0/

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