Potential of Nanocarrier-Based Drug Delivery Systems for Brain Targeting: A Current Review of Literature

Figures & data

Table 1 Various Novel Nanocarrier-Based System and Their Outcomes for Brain Targeting

Nanocarrier-Based System	Targeting Agent	Indication	Outcomes	References
Liposomes	Doxorubicin (DOX)	Glioma	P1NS/TNC-FeLPs have shown GBM-specific cellular uptake and drug release profile. Developed NPs show a thermo-responsive transport, reduced tumor cell proliferation without affecting healthy brain cell function. Less toxic and greater drug accumulation in cancerous cells and long-term survival.	[^Citation38]
Pegylated Liposomes	Doxorubicin	Brain tumor Regression		[^Citation39]
Dendrimers	Borneol and doxorubicin	Dual-functional glioma Targeting	Improved area under the curve (AUC) and drug accumulation in brain tumors, prolonged half-life time and enhanced drug accumulation in glioma cells	[^Citation40]
		Uptake mechanism of dendrimers into brain cells	Enhance permeation and uptake of polyether-copolyester (PEPE) dendrimers across the BBB	[^Citation41]
Polymeric Micelles	Dapoxetine (DPX)	Reduce DPX medication dependence	DPX micelles show improved bioavailability, brain delivery and efficacy across the BBB.	[^Citation42]
Polymeric nanoparticles	Curcumin	Alzheimer’s disease (AD)	Curcumin-loaded CS-BSA NPs penetrated the BBB, activated microglia, and expedited the phagocytosis of the Aβ peptide. Further, NPs showed promise in influencing macrophage polarisation in AD.	[^Citation43]
	Anti-amyloid tibody	Alzheimer’s disease (AD)	Increased absorption and ability to permeate the BBB to target cerebrovascular amyloid formation.	[^Citation44]
Gold nanoparticles (Au-NPs)	L-DOPA	Parkinson’s disease	Developed gold nanoparticles are readily absorbed by brain macrophages and cause no inflammation, effectively permeate the BBB,	[^Citation45]
Quantum dots (QDs)	Aromatic drugs paired α-COOH and NH2 groups	Brain tumor	Selective targeting and imaging to brain cancerous cells	[^Citation46]
	Monoclonal antibodies (Ri7)	Brain endothelial delivery	Ri7-quantum dots complexed form has 4 times larger Vd in brain tissues, complicate endocytosis by brain capillary endothelial cells	[^Citation47]

Figure 1 Novel nanocarriers and their penetration through BBB for brain targeting.

Figure 2 Presentation of the main liposomal medications and targeting agents that improve liposomal affinity and brain targeting.

Figure 3 Scientific approach for ligand-decorated nanoparticles, linked to PEG for brain targeting.

Figure 4 Mechanism of polymeric nanoparticles for brain tumor.

Figure 5 Modified Au nanoparticles for improved BBB penetration with neuron-targeted exosome.

Shi D, Mi G, Shen Y, Webster TJ. Glioma-targeted dual functionalized thermosensitive Ferri-liposomes for drug delivery through an in vitro blood–brain barrier. Nanoscale. 2019;11(32):15057–15071. doi:10.1039/C9NR03931G

 PubMed Web of Science ®Google Scholar

Soliman GM, Sharma R, Choi AO, et al. Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers. Biomaterials. 2010;31(32):8382–8392. doi:10.1016/j.biomaterials.2010.07.039

 PubMedGoogle Scholar

Xu X, Li J, Han S, et al. A novel doxorubicin loaded folic acid conjugated PAMAM modified with borneol, a nature dual-functional product of reducing PAMAM toxicity and boosting BBB penetration. Eur J Pharmaceutical Sci. 2016;88:178–190. doi:10.1016/j.ejps.2016.02.015

 PubMed Web of Science ®Google Scholar

Zhu Y, Liu C, Pang Z. Dendrimer-based drug delivery systems for brain targeting. Biomolecules. 2019;9(12):790. doi:10.3390/biom9120790

 PubMed Web of Science ®Google Scholar

Abourehab MA, Ahmed OA, Balata GF, Almalki WH. Self-assembled biodegradable polymeric micelles to improve dapoxetine delivery across the blood–brain barrier. Int J Nanomedicine. 2018;13:3679. doi:10.2147/IJN.S168148

 PubMed Web of Science ®Google Scholar

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):1–9. doi:10.1186/s11671-018-2759-z

 PubMedGoogle Scholar

Hasadsri L, Kreuter J, Hattori H, Iwasaki T, George JM. Functional protein delivery into neurons using polymeric nanoparticles. J Biol Chem. 2009;284(11):6972–6981. doi:10.1074/jbc.M805956200

 PubMed Web of Science ®Google Scholar

Gonzalez-Carter DA, Ong ZY, McGilvery CM, Dunlop IE, Dexter DT, Porter AE. L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles. Nanomedicine. 2019;15(1):1–11. doi:10.1016/j.nano.2018.08.011

 PubMedGoogle Scholar

Li S, Su W, Wu H, et al. Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids. Nat Biomed Eng. 2020;4(7):704–716. doi:10.1038/s41551-020-0540-y

 PubMed Web of Science ®Google Scholar

Paris-Robidas S, Brouard D, Emond V, Parent M, Calon F. Internalization of targeted quantum dots by brain capillary endothelial cells in vivo. J Cerebral Blood Flow Metab. 2016;36(4):731–742. doi:10.1177/0271678X15608201

 PubMedGoogle Scholar