Bioresorbable polyelectrolytes for smuggling drugs into cells

Abstract

There is ample evidence that biodegradable polyelectrolyte nanocapsules are multifunctional vehicles which can smuggle drugs into cells, and release them upon endogenous activation. A large number of endogenous stimuli have already been tested in vitro, and in vivo research is escalating. Thus, the interest in the design of intelligent polyelectrolyte multilayer (PEM) drug delivery systems is clear. The need of the hour is a systematic translation of PEM-based drug delivery systems from the lab to clinical studies. Reviews on multifarious stimuli that can trigger the release of drugs from such systems already exist. This review summarizes the available literature, with emphasis on the recent progress in PEM-based drug delivery systems that are receptive in the presence of endogenous stimuli, including enzymes, glucose, glutathione, pH, and temperature, and addresses different active and passive drug targeting strategies. Insights into the current knowledge on the diversified endogenous approaches and methodological challenges may bring inspiration to resolve issues that currently bottleneck the successful implementation of polyelectrolytes into the catalog of third-generation drug delivery systems.

Hierarchical Model of Weak Polyelectrolytes with Ionization and Conformation Consistency

“…27 MSA captures the finite-size effect of ions on the electrostatic interactions while reducing to the Debye− Huckel (DH) limiting law at dilute electrolyte concentrations. 28 According to MSA, the change in the excess chemical potential of segment i due to ionization is given by (5) where l B = βe 2 /4πε 0 ε r is the Bjerrum length (7.14 Å for liquid water at room temperature), with e the elementary charge; ε 0 and ε r the vacuum permittivity and dielectric constant of the solvent, respectively; σ i and Z i the hard-sphere diameter and valence of the charged monomer, respectively; η is a parameter related to the ionic asymmetry (i.e., differences in size and valence of the ionic species); and Γ MSA the MSA screening parameter. Approximately, Γ MSA is proportional to the square root of the ionic strength similar to that for the Debye screening parameter.…”

“…Further theoretical development is needed for the rational design of "smart" polymeric systems to achieve their specific functionality such as targeted drug delivery and controlled release, taking advantage of the changes in the ionization and structure of the polymer backbone in response to variations in the pH and composition of the intracellular fluids. 2,5 Ionization of a weak polyelectrolyte in a liquid environment is dependent on the polymer conformation (and vice versa) because of intrachain correlations. While the chargeconformation coupling is relatively insignificant at high polymer volume fractions or high salt concentrations due to the screening effects, the long-range intrachain correlation becomes important in dilute solutions as often encountered in practical applications.…”

“…Due to the long-range nature of electrostatic interactions and intrachain correlation effects and the intrinsic coupling between polymer ionization and conformation changes, it remains a theoretical challenge to accurately describe weak polyelectrolytes in dilute solutions. Further theoretical development is needed for the rational design of “smart” polymeric systems to achieve their specific functionality such as targeted drug delivery and controlled release, taking advantage of the changes in the ionization and structure of the polymer backbone in response to variations in the pH and composition of the intracellular fluids. , …”

Multilayered siRNA nanoparticles as a delivery system for extended gene silencing effect

“…Furthermore, it was also observed that the hollow microcapsule with arginine and chondroitin sulfate disintegrated and releases the drugs after treatment with trypsin-EDTA [90] .…”