Unlocking the potential of chitosan-based polymeric nanoparticles for the treatment of neurological disorders

Document Type : Review Paper

Authors

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Merit University Egypt (MUE), 82755, New Sohag, Egypt

2 International Institute for Halal Research and Training, International Islamic University Malaysia (IIUM), 53100, Kuala Lumpur, Malaysia

3 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), 11837, Cairo, Egypt

Abstract

Neurological disorders are the diseases associated with the central and peripheral nervous system. They are among the most serious and prevalent diseases nowadays. However, most of the pharmacological agents used to treat neurological disorders demonstrate severe toxicities and side effects, along with failure to achieve the desired outcomes due to their inability to cross the blood-brain barrier (BBB). Therefore, efforts have been made to develop potential drug carriers that can enhance the penetration of various therapeutic agents across the BBB. Due to the remarkable selectivity of nanoparticles and their ability to penetrate the BBB, they have attracted enormous interest as a viable solution to overcome these challenges. Polymeric nanoparticles used as drug delivery systems, in particular, demonstrated multiple advantages over traditional drug delivery systems in the treatment of neurological and psychological disorders due to several beneficial properties. This minireview article discusses the current literature on the use of chitosan nanoparticles in particular as promising carriers for delivering therapeutic agents to the brain for the treatment of different neurological diseases. The article emphasizes the advantages of using chitosan over other natural and synthetic polymers, and illustrates the methods of preparation of chitosan nanoparticles, in addition to the characterization of chitosan-based nanoparticles. The article also discusses the specific application of chitosan-based nanoparticles for brain targeting with the aim of the treatment of neurological disorders. Furthermore, challenges and future prospects were also discussed.

Keywords

References

1.     Siddiqi KS, Husen A, Sohrab SS, Yassin MO. Recent status of nanomaterial fabrication and their potential applications in neurological disease management. Nanoscale Res Lett. 2018;13(1):231. 
2.     Lamptey RNL, Chaulagain B, Trivedi R, Gothwal A, Layek B, Singh J. A review of the common neurodegenerative disorders: Current Therapeutic approaches and the potential role of nanotherapeutics. Int J Mol Sci. 2022; 23(3):1851. 
3.     Aderibigbe BA, Naki T. Chitosan-based nanocarriers for nose to brain delivery. Appl Sci. 2019; 9:2219. 
4.     Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem. 2013;2013:238428. 
5.     Caprifico AE, Foot PJS, Polycarpou E, Calabrese G. Overcoming the blood-brain barrier: Functionalised chitosan nanocarriers. Pharmaceutics. 2020;12(11):1013. 
6.     Calzoni E, Cesaretti A, Polchi A, Di Michele A, Tancini B, Emiliani C. Biocompatible polymer nanoparticles for drug delivery applications in cancer and neurodegenerative disorder therapies. J Funct Biomater. 2019;10(1):4. 
7.     Fachel FNS, Medeiros-Neves B, Dal Prá M, Schuh RS, Veras KS, Bassani VL, et al. Box-Behnken design optimization of mucoadhesive chitosan-coated nanoemulsions for rosmarinic acid nasal delivery—In vitro studies. Carbohydr Polym. 2018;199:572–582. 
8.     Bonilla L, Esteruelas G, Ettcheto M, Espina M, García ML, Camins A, et al. Biodegradable nanoparticles for the treatment of epilepsy: From current advances to future challenges. Epilepsia Open. 2022;7(Suppl. 1):S121–S132. 
9.     Pacheco C, Sousa F, Sarmento B. Chitosan-based nanomedicine for brain delivery: Where are we heading? Artif Intell Agric. 2020;146:104430.
10.     Dong X. Current strategies for brain drug delivery. Theranostics. 2018;8(6):1481–1493. 
11.     Keller LA, Merkel O, Popp A. Intranasal drug delivery: opportunities and toxicologic challenges during drug development. Drug Deliv Transl Res. 2022; 12:735–757. 
12.     Boyuklieva R, Pilicheva B. Micro- and nanosized carriers for nose-to-brain drug delivery in neurodegenerative disorders. Biomedicines. 2022;10(7):1706. 
13.     Atkinson AJ. Intracerebroventricular drug administration. Transl Clin Pharmacol. 2017;25(3):117–124. 
14.     Paul G, Pålhagen S, Haegerstrand A, Paul G, Zachrisson O, Varrone A, et al. Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson ’ s disease patients. J Clin Invest. 2015;125(3):1339–1346. 
15.     Mehta AM, Sonabend AM, Bruce JN. Convection-enhanced delivery. Neurotherapeutics. 2017;14(2):358–71. 
16.     Mingozzi F, High KA. Review article immune responses to aav vectors: Overcoming barriers to successful gene therapy. Blood. 2016;122(1):23–37. 
17.     Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: Current perspectives and future challenges. Acta Pharm Sin B. 2016;6(4):287–296. 
18.     Peura L, Malmioja K, Huttunen K, Leppänen J, Hämäläinen M, Forsberg MM, et al. Design, synthesis and brain uptake of lat1-targeted amino acid prodrugs of dopamine. Pharm Res. 2013;30(10):2523–2537. 
19.     Jackson S, George RT, Lodge MA, Piotrowski A, Wahl RL, Gujar SK, et al. The effect of regadenoson on the integrity of the human blood – brain barrier, a pilot study. J Neuro-OncologyOncology. 2017;132(3):513–519. 
20.     Duan L, Li X, Ji R, Hao Z, Kong M, Wen X, et al. Nanoparticle-based drug delivery systems: An inspiring therapeutic strategy for neurodegenerative diseases. 2023; 15(9):2196. 
21.     Moura RP, Martins C, Pinto S, Sousa F, Sarmento B. Blood-brain barrier receptors and transporters: An insight on their function and how to exploit them through nanotechnology. Expert Opin Drug Deliv. 2019; 16(3):271–285.
22.     Stamatovic SM, Johnson AM, Keep RF, Andjelkovic AV. Junctional proteins of the blood-brain barrier: New insights into function and dysfunction. Tissue Barriers. 2016; 4(1): e1154641. 
23.     Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release. 2016;235:34–47. 
24.     Zieli´nska A, Carreiró F, Oliveira AM, Neves A, Pires B, Venkatesh DN, et al. Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology. Molecules. 2019;25(16): 3731. 
25.     Deng S, Gigliobianco MR, Censi R, Di Martino P. Polymeric nanocapsules as nanotechnological alternative for drug delivery system: Current status, challenges and opportunities. Nanomaterials. 2020;10(5):847. 
26.     Sahni JK, Doggui S, Ali J, Baboota S, Dao L, Ramassamy C. Neurotherapeutic applications of nanoparticles in Alzheimer’s disease. J Control Release. 2011;152(2):208–231.
27.     Agrawal M, Saraf S, Saraf S, Dubey SK, Puri A, Gupta U, et al. Stimuli-responsive In situ gelling system for nose-to-brain drug delivery. J Control Release. 2020; 327:235–265. 
28.     Sinha VR, Singla AK, Wadhawan S, Kaushik R, Kumria R, Bansal K, et al. Chitosan microspheres as a potential carrier for drugs. Int J Pharm. 2004;274(1–2):1–33. 
29.     Aibani N, Rai R, Patel P, Cuddihy G, Wasan EK. Chitosan nanoparticles at the biological interface: implications for drug delivery. Pharmaceutics. 2021;13(10):1686. 
30.     Bashir SM, Ahmed Rather G, Patrício A, Haq Z, Sheikh AA, Shah MZ ul H, et al. Chitosan nanoparticles: A versatile platform for biomedical applications. Materials. 2022; 15(19):6521. 
31.     Cortés H, Alcalá-Alcalá S, Caballero-Florán IH, Bernal-Chávez SA, Ávalos-Fuentes A, González-Torres M, et al. A reevaluation of chitosan-decorated nanoparticles to cross the blood-brain barrier. Membranes. 2020;10(9):212.
32.     Gholizadeh H, Cheng S, Pozzoli M, Messerotti E, Traini D, Young P, et al. Smart thermosensitive chitosan hydrogel for nasal delivery of ibuprofen to treat neurological disorders. Expert Opin Drug Deliv. 2019;16(4):453–466. 
33.     Ahmed S, Ikram S. Chitosan based scaffolds and their applications in wound healing. Achiev Life Sci. 2016;10(1):27–37. 
34.     Trapani A, De Giglio E, Cafagna D, Denora N, Agrimi G, Cassano T, et al. Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery. Int J Pharm. 2011;419(1–2):296–307. 
35.     Sahin A, Yoyen-Ermis D, Caban-Toktas S, Horzum U, Aktas Y, Couvreur P, et al. Evaluation of brain-targeted chitosan nanoparticles through blood–brain barrier cerebral microvessel endothelial cells. J Microencapsul. 2017;34(7):659–666. 
36.     Prabaharan M. Review paper: Chitosan derivatives as promising materials for controlled drug delivery. J Biomater Appl. 2008;23(1):5–36. 
37.     Ruby JJ, Pandey VP. Formulation and evaluation of olanzapine loaded chitosan nanoparticles for nose to brain targeting an in vitro and ex vivo toxicity study. J Appl Pharm Sci. 2016;6(9):34–40. 
38.     Hoang NH, Thanh T Le, Sangpueak R, Treekoon J, Saengchan C, Thepbandit W, et al. Chitosan nanoparticles-based ionic gelation method: A promising candidate for plant disease management. Polymers. 2022;14(4):662. 
39.     Karabasz A, Bzowska M, Szczepanowicz K. Biomedical applications of multifunctional polymeric nanocarriers: A review of current literature. Int J Nanomedicine. 2020;15:8673–8696. 
40.     Chhabra R, Tosi G, Grabrucker A. Emerging use of nanotechnology in the treatment of neurological disorders. Curr Pharm Des. 2015;21(22):3111–3130. 
41.     Alper Öztürk A, Çinar Nİ, Yenilmez E. Development of nano-sized ketoprofen lysine incorporated Eudragit® S100 nanomedicine by double emulsion solvent evaporation and in vitro characterization. J Pharm Pharmacogn Res. 2019;7(1):47–58. 
42.     Wang ZH, Wang ZY, Sun CS, Wang CY, Jiang TY, Wang SL. Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain. Biomaterials. 2010;31(5):908–915. 
43.     Sahoo N, Sahoo RK, Biswas N, Guha A, Kuotsu K. Recent advancement of gelatin nanoparticles in drug and vaccine delivery. Int J Biol Macromol. 2015;81:317–331. 
44.     Pan C, Qian J, Zhao C, Yang H, Zhao X, Guo H. Study on the relationship between crosslinking degree and properties of TPP crosslinked chitosan nanoparticles. Carbohydr Polym. 2020; 241:116349. 
45.     Agarwal M, Agarwal MK, Shrivastav N, Pandey S, Das R, Gaur P. Preparation of chitosan nanoparticles and their in-vitro characterization. Int J Life-Sciences Sci Res. 2018; 4(2):1713–1720. 
46.     Elnaggar YSR, Etman SM, Abdelmonsif DA, Abdallah OY. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in alzheimer’s disease: optimization, biological efficacy, and potential toxicity. J Pharm Sci. 2015; 104(10):3544–3556. 
47.     Campolo O, Giunti G, Laigle M, Michel T, Palmeri V. Essential oil-based nano-emulsions: effect of different surfactants, sonication and plant species on physicochemical characteristics. Ind Crops Prod. 2020;157:112935. 
48.     Rasmussen MK, Pedersen JN, Marie R. Size and surface charge characterization of nanoparticles with a salt gradient. Nat Commun. 2020;11:2337. 
49.     Jafarieh O, Md S, Ali M, Baboota S, Sahni JK, Kumari B, et al. Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting. Drug Dev Ind Pharm. 2015;41(10):1674–1681. 
50.     Kang YJ, Cutler EG, Cho H. Therapeutic nanoplatforms and delivery strategies for neurological disorders. Nano Converg. 2018;5(1):35. 
51.     Lustriane C, Dwivany FM, Suendo V, Reza M. Effect of chitosan and chitosan-nanoparticles on post harvest quality of banana fruits. J Plant Biotechnol. 2018;45(1):36–44. 
52.     Md S, Alhakamy NA, Aldawsari HM, Asfour HZ. Neuroprotective and antioxidant effect of naringenin-loaded nanoparticles for nose-to-brain delivery. Brain Sci. 2019;9(10):275. 
53.     De Giglio E, Trapani A, Cafagna D, Sabbatini L, Cometa S. Dopamine-loaded chitosan nanoparticles: Formulation and analytical characterization. Anal Bioanal Chem. 2011; 400(7):1997–2002. 
54.     Fazil M, Md S, Haque S, Kumar M, Baboota S, Sahni JK, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci. 2012;47(1):6–15. 
55.     Nagpal K, Singh SK, Mishra DN. Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety. Int J Biol Macromol. 2013;59:72–83. 
56.     Md S, Haque S, Fazil M, Kumar M, Baboota S, Sahni JK, et al. Optimised nanoformulation of bromocriptine for direct nose-to-brain delivery: Biodistribution, pharmacokinetic and dopamine estimation by ultra-HPLC/mass spectrometry method. Expert Opin Drug Deliv. 2014; 11(6):827–842. 
57.     Anissian D, Ghasemi-Kasman M, Khalili-Fomeshi M, Akbari A, Hashemian M, Kazemi S, et al. Piperine-loaded chitosan-STPP nanoparticles reduce neuronal loss and astrocytes activation in chemical kindling model of epilepsy. Int J Biol Macromol. 2017;107:973–983.
58.     Wilson B, Samanta MK, Santhi K, Kumar KPS, Ramasamy M, Suresh B. Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomedicine Nanotechnology, Biol Med. 2010;6(1):144–152. 
59.  Rukmangathen R, Yallamalli IM, Yalavarthi PR. Formulation and biopharmaceutical evaluation of risperidone-loaded chitosan nanoparticles for intranasal delivery. Drug Dev Ind Pharm. 2019;45(8):1342–1350. 
60.     Zhao Y, Li D, Zhu Z, Sun Y. Improved neuroprotective effects of gallic acid-loaded chitosan nanoparticles against ischemic stroke. Rejuvenation Res. 2019; 23(4):284–292. 
61.     Liu S, Yang S, Ho PC. Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain. Asian J Pharm Sci. 2018;13(1):72–81. 
62.     Wilson B, Samanta MK, Muthu MS, Vinothapooshan G. Design and evaluation of chitosan nanoparticles as novel drug carrier for the delivery of rivastigmine to treat Alzheimer’s disease. Ther Deliv. 2011;2(5):599–609. 
63.     Jain S, Jain R. Design and evaluation of chitosan nanoparticles as novel drug carrier for the delivery of Galantamine to treat Alzheimer’s disease. Parkinsonism Relat Disord. 2018;46:e51. 
64.     Hashemian M, Anisian D, Ghasemi-Kasman M, Akbari A, Khalili-Fomeshi M, Ghasemi S, et al. Curcumin-loaded chitosan-alginate-STPP nanoparticles ameliorate memory deficits and reduce glial activation in pentylenetetrazol-induced kindling model of epilepsy. Prog Neuro-Psychopharmacology Biol Psychiatry. 2017;79:462–471. 
65.     Aluani D, Tzankova V, Yordanov Y, Kondeva-Burdina M, Yoncheva K. In vitro protective effects of encapsulated quercetin in neuronal models of oxidative stress injury. Biotechnol Biotechnol Equip. 2017;31(5):1055–1063. 
66.     Kaur S, Manhas P, Swami A, Bhandari R, Sharma KK, Jain R, et al. Bioengineered PLGA-chitosan nanoparticles for brain targeted intranasal delivery of antiepileptic TRH analogues. Chem Eng J. 2018;346:630–639. 
67.     Ahmad N, Ahmad R, Alam MA, Ahmad FJ. Quantification and brain targeting of eugenol-loaded surface modified nanoparticles through intranasal route in the treatment of cerebral ischemia. Drug Res (Stuttg). 2018;68(10):584–595. 
68.     Yang R, Zheng Y, Wang Q, Zhao L. Curcumin-loaded chitosan–bovine serum albumin nanoparticles potentially enhanced Aβ 42 phagocytosis and modulated macrophage polarization in Alzheimer’s disease. Nanoscale Res Lett. 2018;13(1):330. 
69.     Bashir DJ, Manzoor S, Khan IA, Bashir M, Agarwal NB, Rastogi S, et al. Nanonization of magnoflorine-encapsulated novel chitosan-collagen nanocapsules for neurodegenerative diseases: In vitro evaluation. ACS Omega. 2022;7(8):6472–6480. 
70.     Hassan DM, El-Kamel AH, Allam EA, Bakr BA, Ashour AA. Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson’s disease: Interplay between nuclear factor-kappa β and cathepsin B. Drug Deliv Transl Res. 2024;14(2):400-417.
71.     Nerli G, Robla S, Bartalesi M, Luceri C, D’Ambrosio M, Csaba N, et al. Chitosan coated niosomes for nose-to-brain delivery of clonazepam: Formulation, stability and permeability studies. Carbohydr Polym Technol Appl. 2023;6:100332. 
72.     Saini S, Sharma T, Jain A, Kaur H, Katare OP, Singh B. Systematically designed chitosan-coated solid lipid nanoparticles of ferulic acid for effective management of Alzheimer’s disease: A preclinical evidence. Colloids Surfaces B Biointerfaces. 2021;205:111838. 
73.     Yadav M, Parle M, Sharma N, Dhingra S, Raina N, Jindal DK. Brain targeted oral delivery of doxycycline hydrochloride encapsulated tween 80 coated chitosan nanoparticles against ketamine induced psychosis: Behavioral, biochemical, neurochemical and histological alterations in mice. Drug Deliv. 2017;24(1):1429–1440. 
74.     Shakeri S, Ashrafizadeh M, Zarrabi A, Roghanian R, Afshar EG, Pardakhty A, et al. Multifunctional polymeric nanoplatforms for brain diseases diagnosis, therapy and theranostics. Biomedicines. 2020;8(1):13. 
Nanomedicine Journal
Volume 11, Issue 2
April 2024
Pages 107-118

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