International Peer-Reviewed Journal•Open Access•ISSN 2456-8880
irejournals@gmail.com•+91-7433024337

Home / Current Issue / Paper 1724051

1724051 Vol 10 · Issue 4 Download Paper

Chitosan-Coated Quercetin Lipid Nanoparticles for Intranasal Brain Delivery: A Short Review

Jaya Maurya Anoop Kumar Singh

Subject area: Biological & Medical Sciences  ·  Area of research: Pharmacy

Abstract

Quercetin is a dietary flavonol with well-documented antioxidant and anti-inflammatory activity, and recent studies show that it can also lower amyloid burden, oxidative stress and neuroinflammation in animal models of Alzheimer's disease, Parkinson's disease and stress-related disorders. Its clinical use is limited by very low aqueous solubility (about 0.01 mg/mL), extensive intestinal and hepatic conjugation, and poor access to the brain across the blood–brain barrier. The intranasal route can deliver drugs to the brain along the olfactory and trigeminal nerves and bypasses hepatic first-pass metabolism, but mucociliary clearance removes most conventional nasal formulations within about 10 to 20 minutes. Lipid nanoparticles, particularly nanostructured lipid carriers (NLCs), solubilise lipophilic drugs and protect them from degradation, and coating them with the cationic polysaccharide chitosan adds mucoadhesion and a transient opening of tight junctions. Dispersing the coated particles in a thermosensitive in situ gel can extend residence time further. This short review draws on open online literature to describe the biopharmaceutical problem, the nose-to-brain pathways, lipid nanoparticle design, the intranasal quercetin nanocarriers reported so far, the rationale for chitosan functionalisation, in situ gelling vehicles, and a quality-by-design strategy using a three-factor Box–Behnken design. A staged evaluation plan covering physicochemical, in vitro, ex vivo, safety, stability and in vivo studies is proposed. No study identified in this review combined statistical optimisation, chitosan surface functionalisation of a lipid carrier, quantitative mucoadhesion and ciliotoxicity testing, and an in situ gel for quercetin in one integrated programme, and this gap is the main opportunity identified.

Keywords

quercetin; nanostructured lipid carriers; intranasal delivery; nose-to-brain; chitosan; mucoadhesion; in situ gel; Box-Behnken design; quality by design

References

[1] Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev. 2000;52(4):673–751.

[2] Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84–9.

[3] Satpathy B, Rajwar TK, Mishra A, Saha I, Rai VK, Sahoo RK, et al. Intra-nasal delivery of quercetin-loaded nanostructured lipid carriers (NLCs) in the management of Alzheimer's disease: formulation, in vitro and in vivo assessment. Mol Neurobiol. 2025;62:13182–209. https://doi.org/10.1007/s12035-025-05137-4

[4] Sonawane D, Pokharkar V. Quercetin-loaded nanostructured lipid carrier in situ gel for brain targeting through intranasal route: formulation, in vivo pharmacokinetic and pharmacodynamic studies. AAPS PharmSciTech. 2024;25:30. https://doi.org/10.1208/s12249-024-02736-7

[5] Bazaz MR, Chary PS, Guin S, Mehra NK, Dandekar MP. Nose-to-brain delivery of quercetin-loaded chitosan nanoparticles improves post-traumatic stress disorder-like phenotypes in mice. Eur J Pharmacol. 2026;1012:178477.

[6] Pinheiro RGR, Pinheiro M, Neves AR. Nanotechnology innovations to enhance the therapeutic efficacy of quercetin. Nanomaterials (Basel). 2021;11(10):2658. https://doi.org/10.3390/nano11102658

[7] Almeida AF, Borge GIA, Piskula M, Tudose A, Tudoreanu L, Valentová K, et al. Bioavailability of quercetin in humans with a focus on interindividual variation. Compr Rev Food Sci Food Saf. 2018;17(3):714–31. https://doi.org/10.1111/1541-4337.12342

[8] Pardeshi CV, Belgamwar VS. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targeting. Expert Opin Drug Deliv. 2013;10(7):957–72.

[9] Drath I, Richter F, Feja M. Nose-to-brain drug delivery: from bench to bedside. Transl Neurodegener. 2025;14:23. https://doi.org/10.1186/s40035-025-00481-w

[10] Koo J, Lim C, Oh KT. Recent advances in intranasal administration for brain-targeting delivery: a comprehensive review of lipid-based nanoparticles and stimuli-responsive gel formulations. Int J Nanomedicine. 2024;19:1767–807. https://doi.org/10.2147/IJN.S439181

[11] Illum L. Nasal drug delivery - possibilities, problems and solutions. J Control Release. 2003;87(1–3):187–98.

[12] Müller RH, Radtke M, Wissing SA. Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm. 2002;242(1–2):121–8.

[13] Ways TMM, Lau WM, Khutoryanskiy VV. Chitosan and its derivatives for application in mucoadhesive drug delivery systems. Polymers (Basel). 2018;10(3):267. https://doi.org/10.3390/polym10030267

[14] Pinheiro RGR, Granja A, Loureiro JA, Pereira MC, Pinheiro M, Neves AR, et al. Quercetin lipid nanoparticles functionalized with transferrin for Alzheimer's disease. Eur J Pharm Sci. 2020;148:105314.

[15] International Council for Harmonisation. ICH Harmonised Tripartite Guideline: Validation of Analytical Procedures: Text and Methodology Q2(R1). Geneva: ICH; 2005.

[16] 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). https://doi.org/10.1007/s13346-023-01407-7

[17] Gänger S, Schindowski K. Tailoring formulations for intranasal nose-to-brain delivery: a review on architecture, physico-chemical characteristics and mucociliary clearance of the nasal olfactory mucosa. Pharmaceutics. 2018;10(3):116. https://doi.org/10.3390/pharmaceutics10030116

[18] Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application. Adv Pharm Bull. 2015;5(3):305–13.

[19] Dhawan S, Kapil R, Singh B. Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery. J Pharm Pharmacol. 2011;63(3):342–51. https://doi.org/10.1111/j.2042-7158.2010.01225.x

[20] Kadam T, Agrawal S, Shetty S. Novel nanostructured lipid carriers with lurasidone hydrochloride for intranasal administration for improved bioavailability. Ther Deliv. 2025. https://doi.org/10.1080/20415990.2025.2477440

[21] Revankar AA, Patil AS, Karishetti R, Chougule KR, Patil P, Salokhe A. Enhanced bioavailability of quercetin-loaded niosomal in situ gel for the management of Parkinson's disease. Front Pharmacol. 2025;15:1519649. https://doi.org/10.3389/fphar.2024.1519649

[22] Elkomy MH, Zaki RM, Alsaidan OA, Elmowafy M, Zafar A, Shalaby K, et al. Intranasal nanotransferosomal gel for quercetin brain targeting: I. Optimization, characterization, brain localization, and cytotoxic studies. Pharmaceutics. 2023;15(7):1805. https://doi.org/10.3390/pharmaceutics15071805

[23] Popescu R, Ghica MV, Dinu-Pîrvu CE, Anuța V, Lupuliasa D, Popa L. New opportunity to formulate intranasal vaccines and drug delivery systems based on chitosan. Int J Mol Sci. 2020;21(14):5016. https://doi.org/10.3390/ijms21145016

[24] Gartziandia O, Herran E, Pedraz JL, Carro E, Igartua M, Hernandez RM. Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration. Colloids Surf B Biointerfaces. 2015;134:304–13.

[25] Bruinsmann FA, Pigana S, Aguirre T, Dadalt Souto G, Pereira GG, Bianchera A, et al. Chitosan-coated nanoparticles: effect of chitosan molecular weight on nasal transmucosal delivery. Pharmaceutics. 2019;11(2):86. https://doi.org/10.3390/pharmaceutics11020086

[26] International Council for Harmonisation. ICH Harmonised Tripartite Guideline: Pharmaceutical Development Q8(R2). Geneva: ICH; 2009.

[27] Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25(4):781–91.

[28] Box GEP, Behnken DW. Some new three level designs for the study of quantitative variables. Technometrics. 1960;2(4):455–75.

[29] Ferreira SLC, Bruns RE, Ferreira HS, Matos GD, David JM, Brandão GC, et al. Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta. 2007;597(2):179–93.

[30] International Council for Harmonisation. ICH Harmonised Tripartite Guideline: Stability Testing of New Drug Substances and Products Q1A(R2). Geneva: ICH; 2003.

[31] Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145–9.

[32] Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25–35.

How to cite this paper

Jaya Maurya, Anoop Kumar Singh "Chitosan-Coated Quercetin Lipid Nanoparticles for Intranasal Brain Delivery: A Short Review" Iconic Research And Engineering Journals Volume 10 Issue 4 2026 Page 2523-2537
Jaya Maurya, Anoop Kumar Singh "Chitosan-Coated Quercetin Lipid Nanoparticles for Intranasal Brain Delivery: A Short Review" Iconic Research And Engineering Journals, vol. 10, no. 4, Oct. 2026
Jaya Maurya, Anoop Kumar Singh (2026). Chitosan-Coated Quercetin Lipid Nanoparticles for Intranasal Brain Delivery: A Short Review. Iconic Research And Engineering Journals, 10(4).
Jaya Maurya, Anoop Kumar Singh "Chitosan-Coated Quercetin Lipid Nanoparticles for Intranasal Brain Delivery: A Short Review" Iconic Research And Engineering Journals, vol. 10, no. 4, Oct. 2026.
@article{1724051,
      author = {Jaya Maurya, Anoop Kumar Singh},
      title = {Chitosan-Coated Quercetin Lipid Nanoparticles for Intranasal Brain Delivery: A Short Review},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {4},
      pages = {2523-2537},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1724051.pdf},
      abstract = {Quercetin is a dietary flavonol with well-documented antioxidant and anti-inflammatory activity, and recent studies show that it can also lower amyloid burden, oxidative stress and neuroinflammation in animal models of Alzheimer's disease, Parkinson's disease and stress-related disorders. Its clinical use is limited by very low aqueous solubility (about 0.01 mg/mL), extensive intestinal and hepatic conjugation, and poor access to the brain across the blood–brain barrier. The intranasal route can deliver drugs to the brain along the olfactory and trigeminal nerves and bypasses hepatic first-pass metabolism, but mucociliary clearance removes most conventional nasal formulations within about 10 to 20 minutes. Lipid nanoparticles, particularly nanostructured lipid carriers (NLCs), solubilise lipophilic drugs and protect them from degradation, and coating them with the cationic polysaccharide chitosan adds mucoadhesion and a transient opening of tight junctions. Dispersing the coated particles in a thermosensitive in situ gel can extend residence time further. This short review draws on open online literature to describe the biopharmaceutical problem, the nose-to-brain pathways, lipid nanoparticle design, the intranasal quercetin nanocarriers reported so far, the rationale for chitosan functionalisation, in situ gelling vehicles, and a quality-by-design strategy using a three-factor Box–Behnken design. A staged evaluation plan covering physicochemical, in vitro, ex vivo, safety, stability and in vivo studies is proposed. No study identified in this review combined statistical optimisation, chitosan surface functionalisation of a lipid carrier, quantitative mucoadhesion and ciliotoxicity testing, and an in situ gel for quercetin in one integrated programme, and this gap is the main opportunity identified.},
      keywords = {quercetin; nanostructured lipid carriers; intranasal delivery; nose-to-brain; chitosan; mucoadhesion; in situ gel; Box-Behnken design; quality by design},
      month = {October},
  }