Inverse Thermogelation of Aqueous Triblock Copolymer Solutions into Macroporous Shear-Thinning 3D Printable Inks
Amphiphilic block copolymers that undergo (reversible) physical gelation in aqueous media are of great interest in ditIerent areas including drug delivery, tissue engineering, regenerative medicine, and biofabrication. We investigated a small library of ABA-type triblock copolymers comprising poly(2-methyl-2-oxazoline) as the hydrophilic shell A and different aromatic poly(2-oxazoline)s and poly(2-oxazine)s cores B in an aqueous solution at different concentrations and temperatures. Interestingly, aqueous solutions of poly(2-methyl-2-oxazoline)-block-poly(2-phenyl-2-oxazine)-block-poly(2-methyl-2-oxazoline) (PMeOx-b-PPheOzi-b-PMeOx) undergo inverse thermogelation below a critical temperatur…
Overcoming the PEG-addiction: well-defined alternatives to PEG from structure-property relationships to better defined therapeutics
Synthetic methods in polymer chemistry have evolved tremendously during the last decade. Nowadays more and more attention is devoted to the application of those tools in the development of the next generation of nanomedicines. Nevertheless, poly(ethylene glycol) (PEG) remains the most frequently used polymer for biomedical applications. In this review, we try to summarize recent efforts and developments in controlled polymerisation techniques that may allow alternatives to PEG based systems and can be used to improve the properties of future polymer therapeutics.
From Defined Reactive Diblock Copolymers to Functional HPMA-Based Self-Assembled Nanoaggregates
This paper describes the synthesis of functional amphiphilic poly( N-(2-hydroxypropyl) methacrylamide)-block-poly(lauryl methacrylate) copolymers by RAFT polymerization via the intermediate step of activated ester block copolymers (pentafluoro-phenyl methacrylate). Block copolymers with molecular weights from 12000-28000 g/mol and PDIs of about 1.2 have been obtained. The amphiphilic diblock copolymers form stable super structures (nanoaggregates) by self-organization in aqueous solution. The diameters of these particles are between 100 and 200 nm and depend directly on the molecular weight of the block copolymer. Furthermore, we investigated the impact of these nanoaggregates on cell viabi…
An Inverse Thermogelling Bioink Based on an ABA-Type Poly(2-oxazoline) Amphiphile
Hydrogels are key components in several biomedical research areas such as drug delivery, tissue engineering, and biofabrication. Here, a novel ABA-type triblock copolymer comprising poly(2-methyl-2-oxazoline) as the hydrophilic A blocks and poly(2-phenethyl-2-oxazoline) as the aromatic and hydrophobic B block is introduced. Above the critical micelle concentration, the polymer self-assembles into small spherical polymer micelles with a hydrodynamic radius of approx 8-8.5 nm. Interestingly, this specific combination of hydrophilic and hydrophobic aromatic moieties leads to rapid thermoresponsive inverse gelation at polymer concentrations above a critical gelation concentration (20 wt %) into…
The uptake of N-(2-hydroxypropyl)-methacrylamide based homo, random and block copolymers by human multi-drug resistant breast adenocarcinoma cells
A series of well-defined, fluorescently labelled homopolymers, random and block copolymers based on N-(2-hydroxypropyl)-methacrylamide were prepared by reversible addition–fragmentation chain transfer polymerization (RAFT polymerization). The polydispersity indexes for all polymers were in the range of 1.2–1.3 and the number average of the molar mass (Mn) for each polymer was set to be in the range of 15–30 kDa. The cellular uptake of these polymers was investigated in the human multi-drug resistant breast adenocarcinoma cell line MCF7/ADR. The uptake greatly depended on the polymer molecular mass and structure. Specifically, smaller polymers (approx. 15 kDa) were taken up by the cells at m…
Quo vadis nanomedicine?
The interdisciplinary workshop ‘Quo Vadis Nanomedicine?’ was held on 10–11 April 2014 at the University of Exeter (Exeter, UK), coorganized by the Schumpeter-Research Group ‘Innovations in Nanomedicine’, funded by the VolkswagenStiftung at Exeter University, and the Sonderforschungsbereich (STB; collaborative research centre) 1066 ‘Nanodimensional Polymer Therapeutics for Tumor Therapy’, funded by the German Research Council (DFG) at the Johannes Gutenberg-University (Mainz, Germany). This international workshop brought together scientists, philosophers and social scientists in order to reflect, discuss and rethink the practices, concepts, methods, models and metaphors, as well as the medi…
Development of polymer-based nanoparticles for Zileuton delivery to the lung : PMeOx and PMeOzi surface chemistry reduces interactions with mucins
In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micr…