Influence of Hydrophobic Side-Chain Length in Amphiphilic Gradient Copoly(2-oxazoline)s on the Therapeutics Loading, Stability, Cellular Uptake and Pharmacokinetics of Nano-Formulation with Curcumin

Abstract

Due to the simple one-step preparation method and a promising application in biomedical research, amphiphilic gradient copoly(2-oxazoline)s are gaining more and more interest compared to their analogous block copolymers. In this work, the curcumin solubilization ability was tested for a series of amphiphilic gradient copoly(2-oxazoline)s with different lengths of hydrophobic side-chains, consisting of 2-ethyl-2-oxazoline as a hydrophilic monomer and 2-(4-alkyloxyphenyl)-2-oxazoline as a hydrophobic monomer. It is shown that the length of the hydrophobic side-chain in the copolymers plays a crucial role in the loading of curcumin onto the self-assembled nanoparticles. The kinetic stability of self-assembled nanoparticles studied using FRET shows a link between their integrity and cellular uptake in human glioblastoma cells. The present study demonstrates how minor changes in the molecular structure of gradient copoly(2-oxazoline)s can lead to significant differences in the loading, stability, cytotoxicity, cellular uptake, and pharmacokinetics of nano-formulations containing curcumin. The obtained results on the behavior of the complex of gradient copoly(2-oxazoline)s and curcumin may contribute to the development of effective next-generation polymeric nanostructures for biomedical applications.

Application of stem cells in regeneration medicine

“…Significant advances in nanodrug delivery technology 35 and the continuous development of nanotechnology 36 have led to its application in the field of drug delivery systems 37 . Nanoformulations can selectively target drug transport to fingertip sites, thus reversing the traditional drug delivery process and enabling higher biocompatibility, 38 safety, eco‐friendliness, specificity, and reduced toxicity while maintaining therapeutic efficacy 39 . In addition, nanoformulations can cross the cellular barrier and activate the transport mechanism 40 .…”

Amphiphilic oligo(2-ethyl-2-oxazoline)s via straightforward synthesis and their self-assembly behaviour

“…22 As a result, many amphiphilic POx-based drug delivery systems have been reported for the encapsulation of a number of hydrophobic drugs. [23][24][25][26][27][28][29] In one of the most recent examples, Hoogenboom et al investigated the micellization and drug loading (DL) behaviours of block and gradient analogues of MeOx-PhOx copolymers of varying overall degrees of polymerization (DP). 30 They found very little difference between the DL capacities between gradient copolymers and their block copolymer equivalents and achieved a maximum curcumin DL capacity of 16 wt%.…”