Thermoresponsive and photocrosslinkable polymers can be used as injectable scaffolds in tissue engineering to yield gels in situ with enhanced mechanical properties and stability. They allow easy handling and hold their shapes prior to photopolymerization for clinical practice. Here we report a novel copolymer with both thermoresponsive and photocrosslinkable properties via a facile one-step deactivation enhanced atom transfer radical polymerization (ATRP) using poly(ethylene glycol) methyl ether methylacrylate (PEGMEMA, M(n) = 475) and poly(propylene glycol) methacrylate (PPGMA, M(n) = 375) as monofunctional vinyl monomers and up to 30% of ethylene glycol dimethacrylate (EGDMA) as multifunctional vinyl monomer. The resultant PEGMEMA-PPGMA-EGDMA copolymers have been characterized by gel permeation chromatography (GPC) and 1H NMR analysis, which demonstrate their multivinyl functionality and hyperbranched structures. These water-soluble copolymers show lower critical solution temperature (LCST) behavior at 32 degrees C, which is comparable to poly(N-isopropylacrylamide) (PNIPAM). The copolymers can also be cross-linked by photopolymerization through their multivinyl functional groups. Rheological studies clearly demonstrate that the photocrosslinked gels formed at a temperature above the LCST have higher storage moduli than those prepared at a temperature below the LCST. Moreover, the cross-linking density of the gels can be tuned to tailor their porous structures and mechanical properties by adjusting the composition and concentration of the copolymers. Hydrogels with a broad range of storage moduli from 10 to 400 kPa have been produced.

We report on the synthesis and characterization of hyperbranched dimethylaminoethyl methacrylate (DMAEMA) polymers using reversible addition fragmentation chain transfer polymerization. These polymers are unimolecular and globular and hence interact differently with DNA than conventional DMAEMA or block copolymers. The polymers were shown to effectively bind and condense oligonucleotides (ODNs); visualization of the bound complexes was achieved using atomic force microscopy, whereas isothermal titration calorimetry described the thermodynamics of binding. The ODNs were effectively protected from enzymatic degradation (DNAses) when condensed by all the polycations studied. However, internalization of the complexes into HeLa cells was less effective when the polycation was chain extended with polyethyleneglycol monomethylether methacrylate. Conjugation of folic acid to the periphery of the polycation facilitated much enhanced uptake of the oligomeric DNA into the HeLa cells due to overexpression of folate receptors on the surface of HeLa cells. Although significant cytotoxicity was observed at high polymer concentrations, this could be alleviated by shielding of the polycation using poly(ethyleneglycol monomethylether methacrylate). These results suggest that hyperbranched polymers formed in this way exhibit interesting complexation behavior with ODNs and thus are promising models to study as gene delivery vectors. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Variable architecture polymers are of considerable interest for the delivery of therapeutic biopolymers, such as DNA and proteins, to their site of action. Polymers that can respond with a change in conformation to biologically relevant stimuli, such as temperature and pH, are being carefully designed to take advantage of the change in environmental conditions the polymer-drug conjugate encounters upon progression from larger-scale systems in the body to subcellular compartments. Viruses respond to changes in the cellular environment to gain access to their desired region of cells, and much can be learned from the mechanisms they employ in this effort. However, despite the efficiency of therapeutic biopolymers, undesirable immune and inflammatory responses may result from their repeated administration, so synthetic polymers are an attractive alternative. This mini-review examines a range of recently developed variable architecture polymers, mainly focusing on polymers responsive to temperature and pH, covering both synthetic copolymers and derivatives of naturally occurring polymers for advanced drug delivery applications. The polymers discussed in the article have some of the properties that are most important for polymer drug delivery vehicles to be effective, such as biodegradability, specificity, and biocompatibility.

Polymers designed to change their conformation via a phase transition triggered by acidic cleavage of a hydrophobic side-chain have been synthesized and characterised. The new materials were prepared by co-polymerising N-isopropylacrylamide with an acetal-containing pH-sensitive monomer N-(2-(2,4,6-trimethoxyphenyl)-1,3-dioxan-5-yl)acrylamide (TMPDA) and then grafting the resultant linear co-polymers to branched poly(ethyleneimine). The final three-component polycations exhibited Lower Critical Solution Temperature (LCST) behaviour. The structures of these polymers, their solution behaviour and their self-association were characterized by DLS and TEM in water and buffer solutions. The acid-triggered hydrolysis of trimethoxybenzeneacetal side-chains on the poly(N-isopropylacrylamide-co-TMPDA) grafts resulted in changes in lower critical solution temperatures and in solution self-assembly; thus in effect creating an ‘isothermal’ phase transition. The changes in polymer conformation, at acidity levels corresponding to those in cell endosomes, offer promise for these polymers to act as controlled release materials