Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery

Abstract

In this study, novel hydrogel nanoparticles with dual triggerable release properties based on fibrous structural proteins (keratin) and thermoresponsive copolymers (Pluronic) are introduced. Nanoparticles were used for curcumin delivery as effective and safe anticancer agents, the hydrophobicity of which has limited their clinical applications. A drug was loaded into hydrogel nanoparticles by a single-step nanoprecipitation method. The drug-loaded nanoparticles had an average diameter of 165 and 66 nm at 25 and 37 °C, respectively. It was shown that the drug loading efficiency could be enhanced through crosslinking of the disulfide bonds in keratin. Crosslinking provided a targeted release profile under reductive conditions using an in vivo agent, glutathione (GSH), or in the presence of trypsin. Cytocompatibility assay using HeLa and L929 fibroblast cells exhibited no adverse effect of nanoparticles on cell viability up to 1 mg/mL. Besides, the green fluorescence of curcumin confirmed the uptake of drug-loaded nanoparticles by cancer cells. The redox and temperature-sensitive nanoparticles are potentially useable for the efficient delivery of hydrophobic drugs to targeted regions having a triggerable release profile.

Glycerol–Silicone Elastomers as Active Matrices with Controllable Release Profiles

“…7 A wide variety of sophisticated systems based on different polymers have been designed to modify the release profiles. [8][9][10][11][12] A particularly challenging delivery mode is zero-order, in which the dose of the delivered drug is independent of time or residual concentration in the delivery vehicle. 4,[13][14][15] In general, zero-order release systems are technologically more difficult to create and therefore result in significantly higher prices.…”

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

“…This is particularly useful for delivery of chemotherapeutics to metastatic cancer cells, which have significantly higher concentrations of GSH than healthy cells. Moreover, the high lysine and arginine content in some keratins enables their cleavage by high concentrations of trypsin [ 103 ], which is frequently overexpressed in inflamed tissue [ 104 ]. Thus, keratin could be a useful material when targeting injured or tumorous tissues.…”

Diverse Particle Carriers Prepared by Co‐Precipitation and Phase Separation: Formation and Applications

“…The nanoparticles formed by co‐precipitation are widely used to encapsulate cargos, such as β‐carotene, doxorubicin, paclitaxel, curcumin, insulin, DNA and so on, to solve the problems of low water solubility, poor stability, poor bioavailability and controlled release [54,55,56,57,58,59,60,61,62,63] . Lu et al.…”