Rethinking CRITID Procedure of Brain Targeting Drug Delivery: Circulation, Blood Brain Barrier Recognition, Intracellular Transport, Diseased Cell Targeting, Internalization, and Drug Release

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2021 May 12

PMID 33977060

Citations 50

Authors

Shaobo Ruan

Yang Zhou

Xinguo Jiang

Huile Gao

Affiliations

Soon will be listed here.

Abstract

The past decades have witnessed great progress in nanoparticle (NP)-based brain-targeting drug delivery systems, while their therapeutic potentials are yet to be fully exploited given that the majority of them are lost during the delivery process. Rational design of brain-targeting drug delivery systems requires a deep understanding of the entire delivery process along with the issues that they may encounter. Herein, this review first analyzes the typical delivery process of a systemically administrated NPs-based brain-targeting drug delivery system and proposes a six-step CRITID delivery cascade: circulation in systemic blood, recognizing receptor on blood-brain barrier (BBB), intracellular transport, diseased cell targeting after entering into parenchyma, internalization by diseased cells, and finally intracellular drug release. By dissecting the entire delivery process into six steps, this review seeks to provide a deep understanding of the issues that may restrict the delivery efficiency of brain-targeting drug delivery systems as well as the specific requirements that may guarantee minimal loss at each step. Currently developed strategies used for troubleshooting these issues are reviewed and some state-of-the-art design features meeting these requirements are highlighted. The CRITID delivery cascade can serve as a guideline for designing more efficient and specific brain-targeting drug delivery systems.

Citing Articles

Nebulized seabuckthorn seed oil inhalation attenuates Alzheimer's disease progression in APP/PS1 mice.

Ren R, Zhang G, Ma J, Zheng Y, Zhao Y, Zhang Y Sci Rep. 2025; 15(1):6368.

PMID: 39984555 PMC: 11845625. DOI: 10.1038/s41598-025-89747-x.

Exosome-membrane and polymer-based hybrid-complex for systemic delivery of plasmid DNA into brains for the treatment of glioblastoma.

Lee Y, Kang S, Thuy L, Son M, Park J, Ahn S Asian J Pharm Sci. 2025; 20(1):101006.

PMID: 39931357 PMC: 11808510. DOI: 10.1016/j.ajps.2024.101006.

Peptide-drug conjugates repolarize glioblastoma-associated macrophages to resensitize chemo-immunotherapy of glioblastoma.

Li Z, Jiang S, Wang J, Li W, Yang J, Liu W Sci Adv. 2025; 11(3):eadr8841.

PMID: 39823328 PMC: 11740939. DOI: 10.1126/sciadv.adr8841.

Pathophysiology-Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain.

Wang W, Wang Y, Huang X, Wu P, Li L, Zhang Y Adv Sci (Weinh). 2024; 12(8):e2405483.

PMID: 39716944 PMC: 11848598. DOI: 10.1002/advs.202405483.

Polyinosinic/Polycytidylic Lipid Nanoparticles Enhance Immune Cell Infiltration and Improve Survival in the Glioblastoma Mouse Model.

Brusseler M, Zam A, Moreno-Zafra V, Rouatbi N, Hassuneh O, Marrocu A Mol Pharm. 2024; 21(12):6339-6352.

PMID: 39556101 PMC: 11615939. DOI: 10.1021/acs.molpharmaceut.4c00875.

References

Lajoie J, Shusta E . Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier. Annu Rev Pharmacol Toxicol. 2014; 55:613-31. PMC: 5051266. DOI: 10.1146/annurev-pharmtox-010814-124852. View

Tapeinos C, Battaglini M, Ciofani G . Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. J Control Release. 2017; 264:306-332. PMC: 6701993. DOI: 10.1016/j.jconrel.2017.08.033. View

Dai Y, Xu C, Sun X, Chen X . Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment. Chem Soc Rev. 2017; 46(12):3830-3852. PMC: 5521825. DOI: 10.1039/c6cs00592f. View

Rigotti A, Acton S, Krieger M . The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. J Biol Chem. 1995; 270(27):16221-4. DOI: 10.1074/jbc.270.27.16221. View

Sun H, Su J, Meng Q, Yin Q, Chen L, Gu W . Cancer-Cell-Biomimetic Nanoparticles for Targeted Therapy of Homotypic Tumors. Adv Mater. 2016; 28(43):9581-9588. DOI: 10.1002/adma.201602173. View

Fahn S . Description of Parkinson's disease as a clinical syndrome. Ann N Y Acad Sci. 2003; 991:1-14. DOI: 10.1111/j.1749-6632.2003.tb07458.x. View

Takei H, Rouah E, Ishida Y . Brain metastasis: clinical characteristics, pathological findings and molecular subtyping for therapeutic implications. Brain Tumor Pathol. 2015; 33(1):1-12. DOI: 10.1007/s10014-015-0235-3. View

Champion J, Mitragotri S . Shape induced inhibition of phagocytosis of polymer particles. Pharm Res. 2008; 26(1):244-9. PMC: 2810499. DOI: 10.1007/s11095-008-9626-z. View

Jakob-Roetne R, Jacobsen H . Alzheimer's disease: from pathology to therapeutic approaches. Angew Chem Int Ed Engl. 2009; 48(17):3030-59. DOI: 10.1002/anie.200802808. View

10.

Nathan C . Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006; 6(3):173-82. DOI: 10.1038/nri1785. View

11.

Hak S, Helgesen E, Hektoen H, Huuse E, Jarzyna P, Mulder W . The effect of nanoparticle polyethylene glycol surface density on ligand-directed tumor targeting studied in vivo by dual modality imaging. ACS Nano. 2012; 6(6):5648-58. PMC: 3389615. DOI: 10.1021/nn301630n. View

12.

Antimisiaris S, Mourtas S, Marazioti A . Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery. Pharmaceutics. 2018; 10(4). PMC: 6321407. DOI: 10.3390/pharmaceutics10040218. View

13.

Wohlfart S, Gelperina S, Kreuter J . Transport of drugs across the blood-brain barrier by nanoparticles. J Control Release. 2011; 161(2):264-73. DOI: 10.1016/j.jconrel.2011.08.017. View

14.

Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P . Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron. 2014; 81(1):49-60. DOI: 10.1016/j.neuron.2013.10.061. View

15.

Agarwal R, Kaye S . Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003; 3(7):502-16. DOI: 10.1038/nrc1123. View

16.

Ciechanover A . Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol. 2005; 6(1):79-87. DOI: 10.1038/nrm1552. View

17.

Nellan A, Rota C, Majzner R, Lester-McCully C, Griesinger A, Mulcahy Levy J . Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. J Immunother Cancer. 2018; 6(1):30. PMC: 5925833. DOI: 10.1186/s40425-018-0340-z. View

18.

Song Y, Guo X, Fu J, He B, Wang X, Dai W . Dual-targeting nanovesicles enhance specificity to dynamic tumor cells and manipulation of v3-ligand binding. Acta Pharm Sin B. 2020; 10(11):2183-2197. PMC: 7715539. DOI: 10.1016/j.apsb.2020.07.012. View

19.

Abbott N, Patabendige A, Dolman D, Yusof S, Begley D . Structure and function of the blood-brain barrier. Neurobiol Dis. 2009; 37(1):13-25. DOI: 10.1016/j.nbd.2009.07.030. View

20.

Ruan S, Yuan M, Zhang L, Hu G, Chen J, Cun X . Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials. 2014; 37:425-35. DOI: 10.1016/j.biomaterials.2014.10.007. View