Thermosensitive PCL‐PEG‐PCL hydrogels: Synthesis, characterization, and delivery of proteins

Abstract

In this work, a biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive poly(e-caprolactone)-poly(ethylene glycol)-poly(e-caprolactone) (PCL-PEG-PCL) hydrogels was studied. A series of PCL-PEG-PCL triblock copolymers were synthesized and characterized by 1 H-NMR and gel permeation chromatography (GPC). Thermosensitivity of the PCL-PEG-PCL triblock copolymers was tested using the tube inversion method. The in vitro release behaviors of two model proteins, including bovine serum albumin (BSA) and horseradish peroxidase (HRP), from PCL-PEG-PCL hydrogels were studied in detail. The in vivo gel formation and degradation of the PCL-PEG-PCL triblock copolymers were also investigated in this study. The results showed that aqueous solutions of the synthesized PCL-PEG-PCL copolymers can form in situ gel rapidly after injection under physiological conditions. The PCL-PEG-PCL hydrogels showed the ability to control the release of incorporated BSA and HRP. The released HRP was confirmed to conserve its biological activity by specific enzymatic activity assay. The in vivo gel formation and degradation studies indicated that PCL-PEG-PCL copolymers hydrogels can sustain at least 45 days by subcutaneous injection. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PCL-PEG-PCL copolymers hydrogels show promise as an in situ gelforming controlled drug delivery system for therapeutic proteins.

Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

“…Both PCL-PEG-PCL and PEG-PCL-PEG are biodegradable, and can sustain drug release in an extended period. One could choose to use PCL-PEG-PCL or PEG-PCL-PEG hydrogels according to the practical needs of different applications [107].…”

“…Released HRP was confirmed to preserve its biological activity by specific enzymatic activity assay, in fact gel formation and degradation studies indicated that PCL-PEG-PCL copolymers hydrogels could give a sustained release for at least 45 days by subcutaneous injection. So the great thermosensitivity and biodegradability of these copolymers make them promising gel forming controlled drug delivery system for therapeutic proteins [107].…”

Bulk Compounding of PCL-PEO Blends for 3D Plotting of Scaffolds for Cardiovascular Tissue Engineering

“…From the spectra of the pure materials, it was apparent that the peak at a chemical shift of around 3.6 ppm is representative of PEO. This peak is attributed to the methylene protons of the -CH2-CH2O-in the PEO chain structure [17]. The other peaks can be attributed to PCL, or in the case of the peak around 7.2 ppm, to both polymers.…”

Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines

“…Attempts to increase the stability of poloxamer through the addition of copolymers such as pluronic 25R4 (20), dextran (21), carrageenan (22), and methylcellulose (23) have had limited success. Biodegradable triblock copolymers made up of polycaprolactone (PCL) and polyethyleneglycol (PEG) (i.e., PEG-PCL-PEG, PCL-PEG-PCL) are reported to be stable in aqueous conditions but the crystallinity of the PCL blocks slowed degradation (24)(25)(26). In this study, two novel thermosensitive pentablock copolymers consisting of polyethyleneglycolp o l y c a p r o l a c t o n e -p o l y l a c t i d e -p o l y c a p r o l a c t o n epolyethyleneglycol (PEG-PCL-PLA-PCL-PEG) were studied as injectable hydrogels, with the polylactide (PLA) blocks being added to accelerate the degradation of PCL (27,28).…”