Fine Tuning the Disassembly Time of Thermoresponsive Polymer Nanoparticles.

Abstract

Timed-released disassembly of nanoparticles without a remote trigger or environmental cues is demonstrated in this work. The reversible addition-fragmentation chain transfer (RAFT) polymerization allowed the fine-tuning of the chemical composition in the diblock copolymers, in which the first block consisted of a hydrophilic monomer (DMA) and the second random block consisted of three different monomers: (a) the thermoresponsive NIPAM, (b) the self-catalyzed hydrolyzable DMAEA, and (c) the hydrophobic BA. These diblock copolymers were solubilized in water below the lower critical solution temperature (LCST) of the thermoresponsive second block, and heated to 37 °C (i.e., >LCST) to form small micelle nanoparticles with a narrow particle size distribution. As DMAEA hydrolyzed to acrylic acid groups, the LCST of the diblock increased, and the time at the start of micelle disassembly (t(start)) corresponded to the point where the LCST was equal to the solution temperature (i.e., 37 °C). The high water content in the PNIPAM core allowed an even degradation of the core over time. The copolymer composition allowed fine control over t(start), as this time was linearly dependent upon the BA units in the second block. These nanoparticles could also be designed to be stable (i.e., not disassemble) over a wide pH range or disassemble below a pH of 7.3. Additionally, the time from the start of disassembly to full unimer formation (t(degrade)) could be controlled by the amount of DMAEA units in the second block. A longer t(degrade) (~5.5 h) was found when the number of DMAEA units was 42 compared to t(degrade) of 1.1 h for 25 units. The nanoparticles designed in this work, through fine control of the polymer chemical composition, have the potential for drug delivery purposes for timed-release of drugs and prodrugs and other wide-ranging applications where timed-release would be beneficial.

A direct comparison of linear and star-shaped poly(dimethylaminoethyl acrylate) polymers for polyplexation with DNA and cytotoxicity in cultured cell lines

“…This phenomenon was less apparent over higher pH ranges. Though this seems insignificant but at a lower pH which is correspondent to endosomal pH the PS PDMAEA polymers might have a better buffering capacity [25,26]. Importantly, all the PL and PS PDAEMA polymers zeta potential measurements followed a similar trend of reduction in value as the pH increased, and the zeta potential dropped below zero at pH close to the pKa value of DMAEA.…”

Well-Defined PDMAEA Stars via Cu(0)-Mediated Reversible Deactivation Radical Polymerization

“…14 Additional reports 15 on RAFT, also show a preference to incorporate PDMAEA as the second or third block, instead of using it as a macroinitiator. 16,17 The polymerisation of DMAEA by copper-mediated RDRP techniques is somewhat problematic compared to other acrylates monomers. 18,19 This is attributed to the nucleophilic nature of the tertiary amine on the pendant groups that can react with the secondary halide on the polymer chain end.…”

Self-assembly and morphological transitions of random amphiphilic poly(β-d-glucose-co-1-octyl) phosphazenes

“…[14][15][16][17][18][19] Moreover, through careful molecular design, random amphiphilic copolymers can be induced to form multiple organized self-assemblies, which can be regulated via the balance between hydrophilicity/ hydrophobicity and solvent composition. [24][25][26][27][28] Polyphosphazenes are a class of organic-inorganic hybrid polymers which possess a backbone consisting alternating nitrogen and phosphorus atoms with organic or inorganic groups on each side of each phosphorus atom. Self-assembly by random copolymers has attracted attention due to the simplicity of their synthesis and the common features such as stimuli responsive properties and versatile morphologies for polymeric self assemblies.…”