Drug Delivery with Polymeric Nanocarriers—Cellular Uptake Mechanisms

Abstract

Nanocarrier-based systems hold a promise to become “Dr. Ehrlich’s Magic Bullet” capable of delivering drugs, proteins and genetic materials intact to a specific location in an organism down to subcellular level. The key question, however, how a nanocarrier is internalized by cells and how its intracellular trafficking and the fate in the cell can be controlled remains yet to be answered. In this review we survey drug delivery systems based on various polymeric nanocarriers, their uptake mechanisms, as well as the experimental techniques and common pathway inhibitors applied for internalization studies. While energy-dependent endocytosis is observed as the main uptake pathway, the integrity of a drug-loaded nanocarrier upon its internalization appears to be a seldomly addressed problem that can drastically affect the uptake kinetics and toxicity of the system in vitro and in vivo.

Self-Assembly of Organic Nanomaterials and Biomaterials: The Bottom-Up Approach for Functional Nanostructures Formation and Advanced Applications

“…Moreover, the large number (>500) of monomeric units may favor a more efficient polymer entanglement and a stronger inter-block interaction in comparison with traditional low molecular weight surfactants. Together with the linear AB diblock copolymers, thermoresponsive linear ABA (or BAB) triblock architectures have attracted enormous scientific interest and have already found broad application in material science, biotechnology and nanomedicine [79][80][81]. Furthermore, the use of polymeric amphiphiles represents a promising bottom-up method for the self-assembly processes of organic-inorganic porous materials, in which an (macromolecular) amphiphilic template drives the self-assembly of nanostructures with desired final properties (soft-templating approach) [7,82,83].…”

“…More specifically, the di-and tri-block copolymer of poly(ethylene glycol)/polylactide (PEG/PLA) systems, in the form of both polymer micelles and vesicles (polymersome), are attractive delivery systems since they are biodegradable with a good safety profile and sustained drug delivery [84,85]. The presence of the PEG on the nanocarrier shell prevents the unwanted adsorption of proteins and phagocytes, thereby increasing the period of the blood circulation, while the PLA hydrophobic core can efficiently encapsulate a variety of therapeutic agents [12,80]. Block copolymers micelles, polymersomes and bicontinuous phases exhibit an enhanced efficiency in solubilizing relevant doses of hydrophobic and hydrophilic drugs ( Figure 9A) [85,86].…”

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

“…PNs can be obtained from natural or synthetic polymers, having specific physicochemical features derived from the polymer chemical properties and interactions when assembling the nanostructures. Numerous types of biocompatible and biodegradable polymers from natural or synthetic sources have been reviewed elsewhere [ 62 , 63 , 64 , 65 ]. Among natural polymers, some typical examples include chitosan (CS), dextran, alginate, hyaluronic acid, natural polyelectrolytes such as protamine sulfate (PS), alginic acid, cellulose sulfate, dextran sulfate, heparin and carboxymethylcellulose.…”

Recent trends in protein and peptide-based biomaterials for advanced drug delivery

“…Cell uptake and subcellular trafficking : After reaching the desired tissue, the drug must traverse cell membranes to reach its intracellular target. Cell membranes are permeable to small hydrophobic drugs, but for large and/or hydrophilic drugs, the cell membrane is an impermeable barrier [ [39] , [40] , [41] ]. Once a drug is internalized by a cell, additional barriers within the cell may separate the drug from its therapeutic target.…”