The synthesis of multi-arm poly([R]-3-hydroxybutyrate) (PHB)-based triblock copolymers (poly([R]-3-hydroxybutyrate)-b-poly(N-isopropylacrylamide)-b-[[poly(methyl ether methacrylate)-g-poly(ethylene glycol)]-co-[poly(methacrylate)-g-poly(propylene glycol)]], PHB-b-PNIPAAM-b-(PPEGMEMA-co-PPPGMA), and their subsequent self-assembly into thermo-responsive hydrogels is described. Atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAAM) followed by poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and poly(propylene glycol) methacrylate (PPGMA) was achieved from bromoesterified multi-arm PHB macroinitiators. The composition of the resulting copolymers was investigated by (1) H and (13) C J-MOD NMR spectroscopy as well as size-exclusion chromatography (SEC), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The copolymers featuring different architectures and distinct hydrophilic/hydrophobic contents were found to self-assemble into thermo-responsive gels in aqueous solution. Rheological studies indicated that the linear one-arm PHB-based copolymer tend to form a micellar solution, whereas the two- and four-arm PHB-based copolymers afforded gels with enhanced mechanical properties and solid-like behavior. These investigations are the first to correlate the gelation properties to the arm number of a PHB-based copolymer. All copolymers revealed a double thermo-responsive behavior due to the NIPAAM and PPGMA blocks, thus allowing first the copolymer self-assembly at room temperature, and then the delivery of a drug at body temperature (37 °C). The non-significant toxic response of the gels, as assessed by the cell viability of the CCD-112CoN human fibroblast cell line with different concentrations of the triblock copolymers ranging from 0.03 to 1 mg mL(-1) , suggest that these PHB-based thermo-responsive gels are promising candidate biomaterials for drug-delivery applications.
International audiencePolyhydroxyalkanoate-based diblock copolymers, poly(β-malic acid)-b-poly(3-hydroxybutyrate) (PMLA-b-PHB), featuring different sizes of segments have been synthesized, for the first time, in two steps and in grams quantity. First, the controlled sequential ring-opening polymn. of β-butyrolactone (BL, in bulk) followed by benzyl β-malolactonate (MLABe, in toluene) has been achieved with 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) to afford well-defined poly(benzyl β-malolactonate)-b-poly(3-hydroxybutyrate) (PMLABe-b-PHB) copolymers. A subsequent hydrogenolysis of β-benzyloxycarbonyl units afforded the corresponding PMLA-b-PHB amphiphilic copolymers, as evidenced by 1H, 13C\1H\ and DOSY NMR, SEC, TGA, DSC and contact angle analyses. Next, PMLA-b-PHB copolymers featuring different hydrophilic wt. fractions (10-65%) self-assembled in PBS upon nanopptn. Nano-objects with narrow size distributions (Dh = 17-180 nm; 0.19 \textless PDI \textless 0.30) and exhibiting a neg. surface charge (-32 to -52 mV) were obtained as characterized by DLS, zeta potential, and TEM analyses. Using HepaRG and SK-MEL-28 cells, cytotoxicity studies evidenced no effect on cell viability at low concns. (\textless 88 μg mL-1) while high concns. (88-320 μg mL-1) induced a mild toxicity. Also, high concns. of nanoparticles (ca. 180 μg mL-1) slightly reduced DNA replication while apoptosis measured with DEVD-AMC caspase activity remained unaffected, thus suggesting a moderate cytostatic effect of the nanoparticles without induction of cell death. Furthermore, HepaRG cells were found to efficiently uptake PMLA-b-PHB-based nanoparticles. All these results demonstrated that PMLA-b-PHB copolymers are promising candidates as drug-delivery systems
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.