Timed-Release Polymer Nanoparticles

Abstract

Triggered-release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work. Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA. The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self-assembly and disassembly. At temperatures below the second block's LCST (i.e., below 37 °C for in vitro assays), the diblock copolymer was fully water-soluble, and when heated to 37 °C, the polymer self-assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm. The thermoresponsive nature of the second block could be manipulated in situ by the self-catalyzed degradation of cationic 2-(dimethylamino)ethyl acrylate (DMAEA) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 °C. The disassembly of the nanoparticles could be controlled from 10 to 70 h. The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients.

Hydrolytic charge‐reversal of PEGylated polyplexes enhances intracellular un‐packaging and activity of siRNA

“…1(A,B)]. The rates of hydrolysis observed herein are comparable to previously reported homopolymers of DMAEA studied by Monteiro and coworkers, 39 suggesting that co-polymerization of DMAEA with BMA did not significantly affect hydrolysis. Observable changes in the physicochemical characteristics of HDG-NPs relative to non-HDG-NPs further supported that hydrolysis occurred in the HDG-NPs [ Fig.…”

Nanoparticles of Well‐Defined 4‐Arm Stars made using Nanoreactors in Water

“…We, therefore, designed a nanoreactor that had a similar LCST to the MacroCTA by incorporating a small amount of butyl acrylate in the second block [NR2; P(DMA 70 ‐ b ‐(NIPAM 73 ‐ co ‐BA 7 ))]. The LCST of NR2 started at 25 °C (curve c in Figure ).…”

Polymeric Nanoparticle Engineering: From Temperature-Responsive Polymer Mesoglobules to Gene Delivery Systems

“…Another serious problem, when using polyplexes, is their relatively low cell transfection efficiency. 55 Polyplexes are formed by mixing DNA (or OND) and a cationic polymer (or a copolymer bearing cationic moieties) in aqueous solutions at different molar ratios between the cationic groups of the (co)polymer and the phosphate groups of DNA (N/P). The size of the polyplexes strongly depends on the N/P ratio (Figure 8).…”