Drug targeting to brain: a systematic approach to study the factors, parameters and approaches for prediction of permeability of drugs across BBB

Abstract

The development of a still awaited perfect in vitro model to mimic BBB is a challenging task. System biologist, network biologist and computational technologist should come together to integrate the role of transporters, physiological and pathophysiological complexity of BBB to replicate vascular properties of the brain microcapillaries as a suitable model to facilitate the high-throughput screening of CNS acting biomolecules.

Influence of the formulation on the maximum tolerated doses of brain targeted nanoparticles of gallic acid by oral administration in Wistar rats

“…One of the strategies that has successfully been utilized to improve the therapeutic activity of CNS acting biomolecules is the use of a surface‐modified nanoparticulate drug delivery system . Such nanoparticulate systems should also be accessed for their safety.…”

siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery

“…Advantages of this route came from nasal epithelium high permeability, avoidance of first-pass metabolism and selfadministration. However, this administration damages the nasal mucosa and decreases the quantity of drug available (Alam et al, 2010;Nagpal et al, 2013).…”

Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

“…55 Cell-mediated transcytosis refers only to immune cell-mediated transport. 56 Finally, active efflux transport is another important type of molecule transfer across the BBB that limits brain penetration. This last mechanism involves extrusion of drugs from the CNS back to the blood, thus representing a major impediment to drug therapy.…”

“…These characteristics can contribute to increased drug bioavailability and decreased peripheral toxicity and side effects. 56,57,64,66 Charge and hydrophobicity of the NP surface influence the adsorption of plasmatic proteins, and as a consequence their uptake and/or rate of transcytosis. 67 In the particular case of CNS delivery, NP coating with particular surface stabilizers may be of interest in achieving increased brain drug levels.…”