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Review
. 2022 Dec 5;14(12):2719.
doi: 10.3390/pharmaceutics14122719.

Current Update on Transcellular Brain Drug Delivery

Bhakti Pawar  1 , Nupur Vasdev  1 , Tanisha Gupta  1 , Mahi Mhatre  1 , Anand More  1 , Neelima Anup  1 , Rakesh Kumar Tekade  1
Affiliations
Review

Current Update on Transcellular Brain Drug Delivery

Bhakti Pawar et al. Pharmaceutics. .

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.

Keywords: blood–brain barrier; exosome; nanocarriers; nose-to-brain delivery; peptide; transcytosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the blood–brain barrier and current nanotherapeutics for transcellular brain drug delivery.
Figure 2
Figure 2
Overview of blood–brain barrier and biomolecular exchange.
Figure 3
Figure 3
Various parameters influencing brain permeability.
Figure 4
Figure 4
Different mechanistic pathways in transcellular brain drug delivery.
Figure 5
Figure 5
In vivo organ imaging studies. (A) Optical imaging of various nanoparticles administered at different time intervals. (B) Images of the brain after 24 h of administration. (C) Measurement of fluorescence intensity of the brains among different groups at 24 h. (D) CLSM images showing the build-up of nanoparticles in the brain. Here: * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001. (a) D-D/siRNA; (b) D-DT7/siRNA; (c) D-DCT7/siRNA; (d) D-DTT7/siRNA; (e) D-DTCT7/siRNA. Scale bar represents 50 µm. Adopted with permission from [94].
Figure 6
Figure 6
Various formulation factors must be considered when developing the brain drug delivery system.
Figure 7
Figure 7
Nose-to-brain drug delivery.
Figure 8
Figure 8
PepC7 in vivo distribution. (A) I-Blank control: PBS administered mouse, II-Cy5.5PepC7, III-Cy5.5Pep7, IV-Cy5.5PepSC7. Images were captured after 30 min and 2 h. (B) Similarly, ex vivo organ distribution was studied in the same group as listed in A. Adopted with permission [161].
Figure 9
Figure 9
Mechanistic depiction of the prodrug in brain drug delivery.
Figure 10
Figure 10
Development of the redox-responsive DOX@MSN-S-S-RGD system. Adopted from [221] with permission under license (CC BY 4.0).
See this image and copyright information in PMC

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