Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

Abstract

Targeted nano-drug delivery systems conjugated with specific ligands to target selective cell-surface receptors or transporters could enhance the efficacy of drug delivery and therapy. Transporters are expressed differentially on the cell-surface of different cell types, and also specific transporters are expressed at higher than normal levels in selective cell types under pathological conditions. They also play a key role in intestinal absorption, delivery via non-oral routes (e.g., pulmonary route and nasal route), and transfer across biological barriers (e.g., blood–brain barrier and blood–retinal barrier. As such, the cell-surface transporters represent ideal targets for nano-drug delivery systems to facilitate drug delivery to selective cell types under normal or pathological conditions and also to avoid off-target adverse side effects of the drugs. There is increasing evidence in recent years supporting the utility of cell-surface transporters in the field of nano-drug delivery to increase oral bioavailability, to improve transfer across the blood–brain barrier, and to enhance delivery of therapeutics in a cell-type selective manner in disease states. Here we provide a comprehensive review of recent advancements in this interesting and important area. We also highlight certain key aspects that need to be taken into account for optimal development of transporter-assisted nano-drug delivery systems.

ZnO Nanostructures for Drug Delivery and Theranostic Applications

“…The use of DDS in nanomedicine has important advantages compared with traditional drugs: (i) increasing solubility of drugs that cannot be taken up by cells and increasing therefore their bioavailability [ 27 , 28 ]; (ii) avoiding the degradation of some drugs that are unstable at physiological or gastrointestinal pH [ 29 , 30 ]; and (iii) reducing the toxicity and side effects of drugs by using target molecules that increase the selectivity of the treatment [ 31 , 32 ].…”

Enhanced uptake of gH625 by blood brain barrier compared to liver in vivo: characterization of the mechanism by an in vitro model and implications for delivery

“…Intravenous administration may represent a relatively non-invasive route of drug delivery; however, the BBB is a key obstacle for both small and large molecules 58 , 60 . Improvement of brain delivery and reduction of systemic exposure of drugs are key points which may enable delivery of therapeutics from the bloodstream to the brain 61 , 62 . To better understand and ameliorate the physicochemical properties of peptide drug delivery vectors to improve accumulation on target tissue, biodistribution studies are of great relevance.…”

The Role of Glucose Transporter 1 in Drug Delivery: Transporter, Receptor and/or Signaling Component

“…As the second well-documented mechanism, nanocarrier-GULT1 complex is internalized via transporter-mediated endocytosis. Glucose-modified nanocarrier interacts with GULT1 and produces a complex that is uptaken via clathrin and caveolin mediated endocytosis [18]. A question is raised as to how the modified nanocarrier and GULT1 interaction activates the intercellular endocytosis systems including clathrin and caveolin.…”