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.
Highlights
Polypeptides coming from either natural or synthetic sources are regarded as a class of highly refined polymers closely related with nature
The set of reactions leading to the synthesis of the l-Glu-grafted poly(globaliderandom-pentadecalactone) copolyesters with the l-Glu either protected as benzyl ester (BLG) or with the carboxyl groups in the free form, namely, P[(Glx -r-PDLy )–g–(BLG)z ] and P[(Glx -r-PDLy )–g–(LGA)z ], respectively, are depicted in Scheme 1
A series of P(Glx -r-PDLy ) random copolyesters made of globalide (Gl) and pentadecalactone (PDL) was prepared by enzymatic ring-opening polymerization using Candida antarctica Lipase B (CALB, Novozyme 435)
Summary
Polypeptides coming from either natural or synthetic sources are regarded as a class of highly refined polymers closely related with nature. (a) highly hydrophobic copolyesters with tuned crystallinity and functionality will be feasible by adjusting the content of saturated and unsaturated macrolactones, (b) application of the enzymatic ring-opening polymerization (eROP) to the bio-based ester and peptide building blocks will allow a basically green synthetic procedure suitable for the design of many hybrid copolymers, (c) the bio-based hybrid system that is generated will exhibit a high amphiphilic character as a consequence of the strong contrast between the great hydrophobicity of the long polyester counterpart and the polar nature of the polypeptide side chain, in particular, when the amino acid is in the charged state, and (d) the nanoparticles built from these copolymers should be expected to be highly stable due to the occurrence of strong hydrophobic interactions and due to the tightening effect exerted by the crystallized polyester segments. The particles bearing charged amino acid units will show an efficient loading and pH-dependent release of charged drugs
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