Internal Nanoparticle Structure of Temperature-Responsive Self-Assembled PNIPAM-b-PEG-b-PNIPAM Triblock Copolymers in Aqueous Solutions: NMR, SANS, and Light Scattering Studies

Abstract

In this study, we report detailed information on the internal structure of PNIPAM-b-PEG-b-PNIPAM nanoparticles formed from self-assembly in aqueous solutions upon increase in temperature. NMR spectroscopy, light scattering, and small-angle neutron scattering (SANS) were used to monitor different stages of nanoparticle formation as a function of temperature, providing insight into the fundamental processes involved. The presence of PEG in a copolymer structure significantly affects the formation of nanoparticles, making their transition to occur over a broader temperature range. The crucial parameter that controls the transition is the ratio of PEG/PNIPAM. For pure PNIPAM, the transition is sharp; the higher the PEG/PNIPAM ratio results in a broader transition. This behavior is explained by different mechanisms of PNIPAM block incorporation during nanoparticle formation at different PEG/PNIPAM ratios. Contrast variation experiments using SANS show that the structure of nanoparticles above cloud point temperatures for PNIPAM-b-PEG-b-PNIPAM copolymers is drastically different from the structure of PNIPAM mesoglobules. In contrast with pure PNIPAM mesoglobules, where solidlike particles and chain network with a mesh size of 1-3 nm are present, nanoparticles formed from PNIPAM-b-PEG-b-PNIPAM copolymers have nonuniform structure with "frozen" areas interconnected by single chains in Gaussian conformation. SANS data with deuterated "invisible" PEG blocks imply that PEG is uniformly distributed inside of a nanoparticle. It is kinetically flexible PEG blocks which affect the nanoparticle formation by prevention of PNIPAM microphase separation.

Soluplus solutions as thermothickening materials for topical drug delivery

“…Soluplus is attractive as a thermothickening agent due to its safety, documented by its manufacturer. Many novel temperature‐responsive materials reported in the literature are based on poly(N‐isopropylacrylamide), but this polymer produces cytotoxic hydrolysis products . There is a need to explore macromolecules with known safety profiles to produce temperature‐responsive materials capable of translation into medicines.…”

Fluorophilic–Lipophilic–Hydrophilic Poly(2-oxazoline) Block Copolymers as MRI Contrast Agents: From Synthesis to Self-Assembly

“…Unlike to aqueous solutions, the MeOx-Rf 6 EtOx diblock copolymers were found to be molecularly dissolved in DMSO-d6 ( Figure 5 B). The disagreement between SANS and DLS data where peaks with 100-200 nm were only present on a distribution function is explained by the high sensitivity of DLS to the presence of large aggregates, which obstruct the small particles detection.…”

“…The polymerization kinetics of Rf 6 EtOx was studied according to the standard procedure, being polymerization at 140 o C in acetonitrile with methyl tosylate (MeOTs) as initiator. 43 The conversion of the monomer was followed by gas chromatography, which is plotted in a first order kinetic plot in Figure 1.…”

“…At the same time, PRf 6 EtOx possesses noticeable polarity due to its structure, but still has low ability to form H-bonds. 10 Therefore, we can assume that PMeOx-b-PRf 6 EtOx diblock copolymers form micelles in aqueous solution, whereas in DMSO, where H-bonding effect is much lower; they are molecularly dissolved.…”

“…5 The self-assembly of hydrophilic-hydrophobic block copolymers in solutions is already studied in detail. [6][7][8][9] Nowadays there is a continuous quest for block copolymers that contain two immiscible hydrophobic moieties to further sophisticate their self-assembly. One of the options is to combine lipophilic and fluorophilic fragments in one polymer.…”