Abstract

Human neuroscience has made remarkable progress in understanding basic aspects of functional organization; it is a renowned fact that the blood–brain barrier (BBB) impedes the permeation and access of most drugs to central nervous system (CNS) and that many neurological diseases remain undertreated. Therefore, a number of nanocarriers have been designed over the past few decades to deliver drugs to the brain. Among these nanomaterials, dendrimers have procured an enormous attention from scholars because of their nanoscale uniform size, ease of multi-functionalization, and available internal cavities. As hyper-branched 3D macromolecules, dendrimers can be maneuvered to transport diverse therapeutic agents, incorporating small molecules, peptides, and genes; diminishing their cytotoxicity; and improving their efficacy. Herein, the present review will give exhaustive details of extensive researches in the field of dendrimer-based vehicles to deliver drugs through the BBB in a secure and effectual manner. It is also a souvenir in commemorating Donald A. Tomalia on his 80th birthday.

Highlights

  • Brain diseases are an ever-accelerated challenge in medical care since, with the aging of the world population, the number of patients with brain diseases will multiply, accompanying high social repercussion on account of grievous morbidity and mortality [1]

  • The blood–brain barrier (BBB) is crucial for maintaining brain health and this border is befitting for protecting the brain neurons against harmful and toxic agents that exist in blood, it blocks the penetrance and access of many therapeutic agents [6]

  • Tat peptides were conjugated to bacterial magnetic nanoparticles (Tat-BMPs-PAMAM), which were complexed with small interfering RNA expression plasmid of the human epidermal growth factor receptor gene through electrostatic interplay

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Summary

Introduction

Brain diseases are an ever-accelerated challenge in medical care since, with the aging of the world population, the number of patients with brain diseases will multiply, accompanying high social repercussion on account of grievous morbidity and mortality [1]. Major focus of pharmaceutical, medicinal, and biophysical research has been navigated in exploring and developing novel and simple avenues to achieve enhanced efficacy of the administered agents via investigating various nanoparticle (NP) types, leading to an extensive comprehension of the mechanism of NP uptake in the brain [16] Among these achievements, dendrimers exhibited great potential for a noninvasive treatment [1]. Linking drugs and bioactive compounds or embedding them into a dendritic molecular frame can perfect many correlative biological features, such as bioavailability, solubility, and selectivity In this regard, dendrimers stand for a perfect platform for brain drug delivery. We will delineate the challenges that dendrimers have faced in their clinical translation and discuss how those challenges could be potentially addressed

Physiochemical and Biological Properties of Dendrimers
PAMAM Dendrimers
PPI Dendrimers
PLL Dendrimers
Carbosilane Dendrimers
PPH Dendrimers
Janus Dendrimers
Linear-Dendritic Block Copolymers
Other Types of Dendrimers
Strategies of Dendrimer-Based Nanocarriers for Brain Targeting
Bypassing the BBB with Invasive Approaches
Bypassing the BBB with Noninvasive Approaches
Traversing the BBB with Noninvasive Approaches
Design and Application of Dendrimer-Based DDSs For Brain Targeting
Brain Delivery of Small-Molecule Drugs with Dendrimers
Brain Drug Delivery with Dendrimers for Combination Therapy
Concerns and Future Perspectives
Findings
Conclusions

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