Structural and Rheological Properties of Temperature-Responsive Amphiphilic Triblock Copolymers in Aqueous Media

Abstract

Thermoresponsive amphiphilic biodegradable block copolymers of the type poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) have great potential for various biomedical applications. In the present study, we have surveyed the effects of PEG spacer length (m = 1000 and 1500), temperature, and polymer concentration on the self-assembling process to form supramolecular structures in aqueous solutions of the PCLA-PEG-PCLA copolymer. This copolymer has a lower critical solution temperature, and the cloud point depends on both concentration and PEG length. Thermoreversible hydrogels are formed in the semidilute regime; the gel windows in the phase diagrams can be tuned by the concentration and length of the PEG spacer. The rheological properties of both dilute and semidilute samples were characterized; especially the sol-to-gel transition was examined. Small-angle neutron scattering (SANS) experiments reveal fundamental structural differences between the two copolymers for both dilute and semidilute samples. The intensity profiles for the copolymer with the long PEG spacer could be described by a spherical core-shell model over a broad temperature domain, whereas the copolymer with the short hydrophilic spacer forms rod-like species over an extended temperature range. This finding is supported by cryo-TEM images. At temperatures approaching macroscopic phase separation, both copolymers seem to assume extended rod-like structures.

Non‐Anticoagulant Heparin Prodrug Loaded Biodegradable and Injectable Thermoresponsive Hydrogels for Enhanced Anti‐Metastasis Therapy

“…Figure 1 shows the 1 H NMR spectrum of the block copolymer with the characteristic peaks of PEG, poly(caprolactone), and poly(lactide) at signal a (δ = 3.60 ppm), signal f (δ = 4.03 ppm), and signal b (δ = 5.12 ppm), respectively. [37] The number average molecular weight ( M n ) of the block copolymer was calculated using the characteristic peaks signals of PEG, CL, and LA in the 1 H NMR spectrum, according to previously reported Equations and *Note: n is the number of repeating units, LA and CL, per polymer chain, and x is theoretical proton number of the repeating unit, ethylene glycol, in PEG per mole.…”

“…Molecular structure of the Nac‐hep‐triBLOCK was examined using 1 H NMR spectroscopy ( Figure 3 ). Presence of the characteristic signals of CH2CH2O (≈3.62) for ethylene glycol, CH2CHCH2 (≈2.42) for CL, and CH2C H2 CH2 (≈1.53) for PCLA at Nac‐hep‐triBLOCK, along with heparin proton (labeled in the red circular area), indicated the successful synthesis of Nac‐hep‐PCLA . The molecular weight and distribution of polymers were determined by GPC.…”

“…The gel formation process occurs through self‐assembly of amphiphilic copolymers by various non‐covalent forces, including hydrophobic interactions and hydrogen bonding between copolymers . The temperature‐dependent gel formation window of the polymer has been attributed to a critical balance of hydrophilic and hydrophobic moieties, which is also controlled by adjusting the weight percent concentration of the polymer solution . Heparin, significantly contributing to hydrophilicity in the polymer system, also disrupts the hydrophilic and hydrophobic balance after conjugation with triBLOCK, such that the hydrophobic moieties are dominated by the hydrophilic polymer sections.…”

“…Sol–gel phase transitions of the triBLOCK and triBLOCK mixed heparin‐loaded triBLOCK (Nac‐hep‐triBLOCK:triBLOCK (1:3)) were determined using the tube‐inversion method, in which the sample vials were inverted and the flow of the different states was then observed for 1 min . Briefly, the optimum tuned ratios were selected using a viscosity test.…”

“…The PCLA‐PEG‐PCLA hydrogel is characterized by its capacity to undergo reversible volume‐phase transitions in response to subtle changes in the surrounding temperature. This temperature‐dependent deformation of PCLA‐PEG‐PCLA hydrogel has been attributed to a critical balance of hydrophilic PEG and hydrophobic PCLA moieties within the polymer network . The sol–gel phase transition temperature and gel formation window could, therefore, be easily controlled by adjusting the balance of the hydrophilic and hydrophobic moieties and/or the weight percent concentration of the polymer solution.…”