Current Update on Transcellular Brain Drug Delivery

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Dec 23

PMID 36559214

Authors

Bhakti Pawar

Nupur Vasdev

Tanisha Gupta

Mahi Mhatre

Anand More

Neelima Anup

Rakesh Kumar Tekade

Affiliations

Soon will be listed here.

Abstract

It is well known that the presence of a blood-brain barrier (BBB) makes drug delivery to the brain more challenging. There are various mechanistic routes through which therapeutic molecules travel and deliver the drug across the BBB. Among all the routes, the transcellular route is widely explored to deliver therapeutics. Advances in nanotechnology have encouraged scientists to develop novel formulations for brain drug delivery. In this article, we have broadly discussed the BBB as a limitation for brain drug delivery and ways to solve it using novel techniques such as nanomedicine, nose-to-brain drug delivery, and peptide as a drug delivery carrier. In addition, the article will help to understand the different factors governing the permeability of the BBB, as well as various formulation-related factors and the body clearance of the drug delivered into the brain.

Citing Articles

Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ-on-a-Chip Technology.

Pramotton F, Spitz S, Kamm R Adv Sci (Weinh). 2024; 11(32):e2403892.

PMID: 38922799 PMC: 11348103. DOI: 10.1002/advs.202403892.

Progress of nanoparticle drug delivery system for the treatment of glioma.

Lai G, Wu H, Yang K, Hu K, Zhou Y, Chen X Front Bioeng Biotechnol. 2024; 12:1403511.

PMID: 38919382 PMC: 11196769. DOI: 10.3389/fbioe.2024.1403511.

Nanomaterial-Based Strategies for Attenuating T-Cell-Mediated Immunodepression in Stroke Patients: Advancing Research Perspectives.

Wang Y, Liu C, Ren Y, Song J, Fan K, Gao L Int J Nanomedicine. 2024; 19:5793-5812.

PMID: 38882535 PMC: 11180442. DOI: 10.2147/IJN.S456632.

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

Liu Y, Liang Y, Yuhong J, Xin P, Han J, Du Y Drug Des Devel Ther. 2024; 18:1469-1495.

PMID: 38707615 PMC: 11070169. DOI: 10.2147/DDDT.S447496.

Non-Invasive Drug Delivery across the Blood-Brain Barrier: A Prospective Analysis.

Niazi S Pharmaceutics. 2023; 15(11).

PMID: 38004577 PMC: 10674293. DOI: 10.3390/pharmaceutics15112599.

References

Rojas O, Probstel A, Porfilio E, Wang A, Charabati M, Sun T . Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10. Cell. 2019; 176(3):610-624.e18. PMC: 6903689. DOI: 10.1016/j.cell.2018.11.035. View

Georgieva J, Hoekstra D, Zuhorn I . Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier. Pharmaceutics. 2014; 6(4):557-83. PMC: 4279133. DOI: 10.3390/pharmaceutics6040557. View

Kiessling M, Herchenhan E, Eggert H . Cerebrovascular and metabolic effects on the rat brain of focal Nd:YAG laser irradiation. J Neurosurg. 1990; 73(6):909-17. DOI: 10.3171/jns.1990.73.6.0909. View

Pardridge W . Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv. 2004; 3(2):90-105, 51. DOI: 10.1124/mi.3.2.90. View

Khan M, Filipczak N, Torchilin V . Cell penetrating peptides: A versatile vector for co-delivery of drug and genes in cancer. J Control Release. 2020; 330:1220-1228. DOI: 10.1016/j.jconrel.2020.11.028. View

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

Bobbie M, Roy S, Trudeau K, Munger S, Simon A, Roy S . Reduced connexin 43 expression and its effect on the development of vascular lesions in retinas of diabetic mice. Invest Ophthalmol Vis Sci. 2010; 51(7):3758-63. PMC: 2904019. DOI: 10.1167/iovs.09-4489. View

Manta K, Papakyriakopoulou P, Chountoulesi M, Diamantis D, Spaneas D, Vakali V . Preparation and Biophysical Characterization of Quercetin Inclusion Complexes with β-Cyclodextrin Derivatives to be Formulated as Possible Nose-to-Brain Quercetin Delivery Systems. Mol Pharm. 2020; 17(11):4241-4255. DOI: 10.1021/acs.molpharmaceut.0c00672. View

He Q, Liu J, Liang J, Liu X, Li W, Liu Z . Towards Improvements for Penetrating the Blood-Brain Barrier-Recent Progress from a Material and Pharmaceutical Perspective. Cells. 2018; 7(4). PMC: 5946101. DOI: 10.3390/cells7040024. View

10.

Eckford P, Sharom F . ABC efflux pump-based resistance to chemotherapy drugs. Chem Rev. 2009; 109(7):2989-3011. DOI: 10.1021/cr9000226. View

11.

Erickson M, Dohi K, Banks W . Neuroinflammation: a common pathway in CNS diseases as mediated at the blood-brain barrier. Neuroimmunomodulation. 2012; 19(2):121-30. PMC: 3707010. DOI: 10.1159/000330247. View

12.

Koenderink J, van den Heuvel J, Bilos A, Vredenburg G, Vermeulen N, Russel F . Human multidrug resistance protein 4 (MRP4) is a cellular efflux transporter for paracetamol glutathione and cysteine conjugates. Arch Toxicol. 2020; 94(9):3027-3032. PMC: 7415487. DOI: 10.1007/s00204-020-02793-4. View

13.

Zhang J, Sadowska G, Chen X, Park S, Kim J, Bodge C . Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. FASEB J. 2015; 29(5):1739-53. PMC: 4771067. DOI: 10.1096/fj.14-258822. View

14.

Colabufo N, Berardi F, Contino M, Niso M, Perrone R . ABC pumps and their role in active drug transport. Curr Top Med Chem. 2009; 9(2):119-29. DOI: 10.2174/156802609787521553. View

15.

Hagan N, Ben-Zvi A . The molecular, cellular, and morphological components of blood-brain barrier development during embryogenesis. Semin Cell Dev Biol. 2015; 38:7-15. DOI: 10.1016/j.semcdb.2014.12.006. View

16.

Liao C, Wang S, Chen Y, Wang H, Wu J . Lipopolysaccharide-induced inhibition of connexin43 gap junction communication in astrocytes is mediated by downregulation of caveolin-3. Int J Biochem Cell Biol. 2010; 42(5):762-70. DOI: 10.1016/j.biocel.2010.01.016. View

17.

Courousse T, Gautron S . Role of organic cation transporters (OCTs) in the brain. Pharmacol Ther. 2014; 146:94-103. DOI: 10.1016/j.pharmthera.2014.09.008. View

18.

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

19.

Zhou J, Patel T, Sirianni R, Strohbehn G, Zheng M, Duong N . Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proc Natl Acad Sci U S A. 2013; 110(29):11751-6. PMC: 3718184. DOI: 10.1073/pnas.1304504110. View

20.

Johnsen K, Burkhart A, Thomsen L, Andresen T, Moos T . Targeting the transferrin receptor for brain drug delivery. Prog Neurobiol. 2019; 181:101665. DOI: 10.1016/j.pneurobio.2019.101665. View