Copolymacrolactones Grafted with l-Glutamic Acid: Synthesis, Structure, and Nanocarrier Properties

Abstract

The enzymatic ring-opening copolymerization (eROP) of globalide (Gl) and pentadecalactone (PDL) was performed in solution from mixtures of the two macrolactones at ratios covering the whole range of comonomeric compositions. The resulting P(Glx-r-PDLy) random copolyesters were aminofunctionalized by thiol-ene reaction with aminoethanethiol. ROP of γ-benzyl-l-glutamate N-carboxyanhydride initiated by P(Glx-r-PDLy)-NH2 provided neutral poly(γ-benzyl-l-glutamate)-grafted copolyesters, which were converted by hydrolysis into negatively charged hybrid copolymers. Both water-soluble and nonsoluble copolymers were produced depending on copolymer charge and their grafting degree, and their capacity for self-assembling in nano-objects were comparatively examined. The emulsion solvent-evaporation technique applied to the chloroform-soluble copolymers grafted with benzyl glutamate rendered well-delineated spherical nanoparticles with an average diameter of 200–300 nm. Conversely, micellar solutions in water were produced from copolyesters bearing grafted chains composed of at least 10 units of glutamic acid in the free form. The copolymer micelles were shown to be able to load doxorubicin (DOX) efficiently through electrostatic interactions and also to release the drug at a rate that was markedly pH dependent.

Enzymatic recycling of polymacrolactones

“…This signal split into different peaks for PGl because this PML is polymerized from a mixture of four diasteroisomeric, two positional and two geometric isomeric macrolactones. 60 As expected, these peaks were not observed for the saturated PPDL polymacrolactone. Both the oxymethylene signal at 4.1 ppm and the signal due to the methylene group attached to the hydroxyl end group at 3.6 ppm, respectively, were used for the determination of the number average molecular weights of the synthesized PMLs (Table 1).…”

“…The average Δ E for Gl MCOs has been estimated as the weighted average of each combination, taking their relative populations that were obtained from experimental data (Table S1‡). 60…”

Elastomeric copolyesters of ω-pentadecalactone and cyclohexylenedimethylene succinate obtained by enzymatic polymerization

“…Enzymatic copolymerization of ω-pentadecalactone with hydrophilic monomers such as p-dioxanone or butylene and propylene carbonates allowed to obtain random copolyesters with enhanced hydrolytic and enzymatic degradability [31][32][33][34]. On the other hand the enzymatic copolymerization with ε-caprolactone or globalide allowed the synthesis of copolyesters that could crystallize isomorphically over the whole range of compositions [35,36]. In order to reduce the crystallinity of this polyester, copolymerization with branched lactones such as ε-decalactone or δ-hexalactone was carried out and allowed to obtain copolyesters with tuned properties [22,37,38].…”

Synthesis of Functionalized Triblock Copolyesters Derived from Lactic Acid and Macrolactones for Bone Tissue Regeneration

“…In fact, our research group has already validated the functionalization of unsaturated polymacrolactones with polypeptides via thiol-ene reactions and it might be valuable for these triblock copolymers. [47][48][49]…”