Modular Design of Redox-Responsive Stabilizers for Nanocrystals

Abstract

Many potent drugs are difficult to administer intravenously due to poor aqueous solubility. A common approach for addressing this issue is to process them into colloidal dispersions known as "nanocrystals" (NCs). However, NCs possess high-energy surfaces that must be stabilized with surfactants to prevent aggregation. An optimal surfactant should have high affinity for the nanocrystal's surface to stabilize it, but may also include a trigger mechanism that could offer the possibility of altering size distribution and uptake of the NC. This study presents a modular and systematic strategy for optimizing the affinity of polymeric stabilizers for drug nanocrystals both before and after oxidation (i.e., the selected trigger), thus allowing for the optimal responsiveness for a given application to be identified. A library of 10 redox-responsive polymer stabilizers was prepared by postpolymerization modification, using the thiol-yne reaction, of two parent block copolymers. The stabilizing potential of these polymers for paclitaxel NCs is presented as well as the influence of oxidation on size and dissolution following exposure to reactive oxygen species (ROS), which are strongly associated with chronic inflammation and cancer. Owing to the versatility of postpolymerization modification, this contribution provides general tools for preparing triggered-sheddable stabilizing coatings for nanoparticles.

In Vitro and In Vivo Evaluation of PEGylated Layer‐by‐Layer Polyelectrolyte‐Coated Paclitaxel Nanocrystals

“…Drug Release and Calculation of Half‐Life of Drug Release (t ½ ) : Dissolution of the PTX formulations was studied under sink conditions using an adapted protocol from the literature . Briefly, a Float‐A‐Lyzer G2 unit (1 mL, MWCO: 100 kDa, Sigma‐Aldrich, Buchs, Switzerland) was filled with 1 mL of the release medium (10 × 10 −3 m phosphate buffer pH 7.4, containing 5 wt% BSA) and a small volume of concentrated formulation (maximum 50 µL) was added to reach a PTX concentration of 0.025 mg mL –1 .…”

“…Indeed, in spite of benefits such as markedly reduced risk of hypersensitivity reactions, lower incidence of neuroptenia, and linear pharmacokinetics compared to the surfactant‐based Taxol formulation, Abraxane is unable to optimally exploit the enhanced permeability and retention (EPR) effect due to rapid dissolution . Among the strategies investigated for slowing the dissolution of anticancer drug NCs, stabilizing coatings produced by the layer‐by‐layer (LbL) assembly of polyelectrolytes are one of the few to have shown some success. Indeed, polyelectrolyte multilayers have been used to slow the dissolution of PTX, camptothecin, and tamoxifen NCs .…”

CO2-responsive polymeric materials: synthesis, self-assembly, and functional applications

“…77 Switchable surfactants can address the above-mentioned concerns. [89][90][91][92][93][94] In most cases, addition of acid, base, oxidant, or reductant is required, which causes environmental impact due to the wastewater produced in subsequent washing steps. 2 This is an advantage in latex production since the stability of the latex is not always necessary.…”

Functional Colloidal Stabilization

“…These synthesized stabilizers provide general tools for preparing triggered-cleavable stabilized nanoparticles for imaging and coatings for nanocrystals. [90] 3.2.1.5. Magnetic Responsive Surfactants: Magnetically responsive surfactants as molecular magnets were reviewed extensively by Eastoe et al [91] Magnetic surfactants are divided into magnetic ionic liquids, chelating surfactants, polyoxometalate surfactants, organic-based molecular magnets, and nonidentical magnetic centers.…”