Synthesis, self-assembly and stimuli responsive properties of cholesterol conjugated polymers

Abstract

Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to generate welldefined pH-responsive biofunctional polymers as potential 'smart' gene delivery systems. A series of five poly(dimethylamino ethyl methacrylate-co-cholesteryl methacrylate) P(DMAEMA-co-CMA) statistical copolymers, with similar molecular weights and varying cholesterol content, were prepared. The syntheses, compositions and molecular weight distributions for P(DMAEMA-co-CMA) were monitored by nuclear magnetic resonance (NMR), solid-state NMR and gel permeation chromatography (GPC) evidencing well-defined polymeric structures with narrow polydispersities. Aqueous solution properties of the copolymers were investigated using turbidimetry and light scattering to determine hydrodynamic diameters and zeta potentials associated with the phase transition behaviour of P(DMAEMA-co-CMA) copolymers. UV-Visible spectroscopy was used to investigate the pH-responsive behaviour of copolymers. Hydrodynamic radii were measured in the range 10-30 nm (pH, temperature dependent) by dynamic light scattering (DLS). Charge studies indicated that P(DMAEMA-co-CMA) polymers have an overall cationic charge, mediated by pH. Potentiometric studies revealed that the buffering capacity and pK a values of polymers were dependent on cholesterol content as well as on cationic charge. The buffering capacity increased with increasing charge ratio, overall demonstrating transitions in the pH endosomal region for all five copolymeric structures. Cell viability assay showed that the copolymers displayed increasing cytotoxicity with decreasing number of cholesterol moieties. These preliminary results show the potential of these welldefined P(DMAEMA-co-CMA) polymers as in vitro siRNA delivery agents.

RAFT Inverse Microemulsion Polymerization: Effects of Monomer Solubility and Different Types of Initiators

“…The synthesis of PDMAEMA via RAFT process is extensively reported, and a reference reaction in solution presented kinetic and molar mass results in agreement with an expected RAFT process: linear pseudo‐first‐order plot, unimodal SEC traces with proper shifts to lower elution volumes with conversion, narrow MMDs ( M w / M n < 1.5), and linear increase of M n with conversion close to the theoretical values (see Figure S5 in the Supporting Information). Based on these results, and assuming no CTA degradation, it could be concluded that the IMEPs in presence of CEP does not present any characteristic of a RAFT process.…”

“…Recently, copolymers containing 2‐(dimethylamino)­ethyl methacrylate (DMAEMA) have attracted attention due to its stimuli‐responsive properties and potential applications in nanomedicine . Therefore, the synthesis of poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) using a dispersed polymerization system seems to be interesting route to obtain well‐defined hydrophilic nanoparticles .…”

Synthesis of cationic star polymers by simplified electrochemically mediated ATRP

“…1 H NMR spectrum shown in Figure 9 confirms the structure of β-CD-(PDMAEMA 28 ) 21 3 (α), -CH 2 -(β), -CH 3 (g), -CH 2 -(f), and -OCH 2 -(e) groups of the PDMAEMA units in the arms, respectively, indicating the presence of PDMAEMA chains [65]. While, in the 1 H NMR spectrum of the star block copolymer (Figure 10 Table 1, entry 5; M n = 97 100, Ð = 1.08) after purification (in CDCl 3 ) arms, respectively, indicating the presence of PBA chains [15].…”

A new proton sponge polymer synthesized by RAFT polymerization for intracellular delivery of biotherapeutics

“…polyethyleneimine (branched, M n : 25 kDa and 60 kDa; and linear, M n : 8 kDa). A protocol reported previously 31 was followed for determination of the proton sponge capacity of polymers. In these experiments, either the molar concentration of polymers or the repeating units in polymers were kept constant to be able to compare the proton sponge capacity of different types of polymers tested (i.e.…”