Synthesis And Properties Of Biodegradable Aliphatic Polyesters, Their Polypseudorotaxanes, And The Related Glycopolymers

Owing to their excellent biodegradability and biocompatibility, both poly(ε-carpolactone)(PCL) and polylactides have been widely used for drug delivery systems and tissue engineering. However, because of the high degree of crystallization and the hydrophobic polymer backbone, their in vitro / in vivo degradation rate usually can not be controlled. Moreover, their poor compatibility with protein drugs, even with cells, greatly hampered their clinical applications. To this end, the regulation of the polymer's hydrophilicity-hydrophobicity balance, and the control of macromolecular architecture and compostition, have become an important way to improve their properties.(1) Supramolecular Polypseudorotaxanes Composed of Star-Shaped Porphyrin-Cored Poly(ε-caprolactone) andα-CyclodextrinStar-shaped porphyrin-cored poly(ε-caprolactone) (SPPCL) was synthesized using a tetra-hydroxyethyl terminated porphyrin as a core initiator and stannous octoate as a catalyst in bulk at 120℃. The molecular weight of as-synthesized polymer could be adjusted linearly by controlling the molar ratio ofε-caprolactone to porphyrin core initiator, and the molecular weight distribution was reasonably narrow. Supramolecular polypseudorotaxanes were prepared by the inclusion complexation of SPPCL withα-cyclodextrin (α-CD). The results demonstrated that the porphyrin-cored polypseudorotaxanes formed throughα-CD molecules threading onto the branch chains of star-shaped SPPCL polymers, and they had a channel-type crystalline structure. Meanwhile, the original crystallization of SPPCL polymers within the polypseudorotaxanes was completely suppressed in theα-CD cavities both the SPPCL polymers and the polypseudorotaxanes showed similar fluorescent and UV-vis spectra compared with porphyrin core initiator. Furthermore,α-CD molecule to some extent improves the hydrophilicity of SPPCL polymers. (2) Synthesis, self-assembly and recognition properties of amphiphilic star-shaped poly(ε-caprolactone)-b-poly(gluconamidoethyl methacrylate) block copolymersAmphiphilic star-shaped poly(ε-caprolactone)-b-poly(gluconamidoethyl methacrylate)block copolymers (SPCL-PGAMA) were synthesized from the atom transfer radical polymerization (ATRP) of unprotected GAMA glycomonomer using a tetra(2-bromo-2-methylpropionyl)-terminated poly(ε-caprolactone) (SPCL-Br) as a macroinitiator in NMP solution at room temperature. The block length of glycopolymer within as-synthesized SPCL-PGAMA copolymers could be adjusted linearly by controlling the molar ratio of GAMA glycomonomer to SPCL-Br macroinitiator, and the molecular weight distribution was reasonably narrow. The degree of crystallization of PCL block within copolymers decreased with the increasing block length ratio of outer PGAMA to inner PCL. The morphology of self-assembled aggregates in aqueous solution could be conveniently transformed by the weight fraction of hydrophilic PGAMA block, which changed from spherical micelles, worm-like aggregates, to vesicles. Furthermore, the biomolecular binding of SPCL-PGAMA with Concanavalin A (ConA) was studied by means of UV-vis, fluorescence, and DLS, which demonstrated that these SPCL-PGAMA copolymers had specific recognition with ConA. In addition, the sugar-installed micelles were very stabe in aqueous solution at 37℃, which provides star-shaped SPCL-PGAMA block copolymers for targeted drug delivery.(3) Supramolecular and Biomimetic Polypseudorotaxane/Glycopolymer Biohybrids: Synthesis, Glucose-Surfaced Nanoparticles, and Recognition with LectinA new class of supramolecular and biomimetic glycopolymer/ poly(ε-caprolactone)-based polypseudorotaxane/glycopolymer triblock copolymers (poly(D-gluconamidoethylmethacrylate) -PPR-poly(D-gluconamidoethylmethacrylate), denoted as (PGAMA-PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, were synthesized by the combination of ring-opening polymerization ofε-caprolactone, supramolecular inclusion reaction, and the direct atom transfer radical polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA) glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion complexation of biodegradable poly(ε-caprolactone) (PCL) withα-cyclodextrin (α-CD), in which the crystalline PCL segments were included into the hydrophobicα-CD cavities and their crystallization was completely suppressed. Moreover, the self-assembled aggregates from these triblock copolymers have a hydrophilic glycopolymer shell and an oligosaccharide threaded polypseudorotaxane core, which changed from spherical micelles to vesicles with the decreasing weight fraction of glycopolymer segments. Furthermore, it was demonstrated that these triblock copolymers had specific biomolecular recognition with Concanavalin A (ConA) in comparison with bovine serum albumin (BSA).(4) Synthesis, characterization and properties of amphiphilic dendrimer-like poly(ε-caprolactone) -b-glycopolymer block copolymersDendrimer-like poly(ε-caprolactone)-b-poly(D-gluconamidoethylmethacrylate) block copolymers (i.e, PAMAM-PCL-PGAMA) have been successfully synthesized via the ROP of CL monomer using a poly(amidoamine) dendrimer (PAMAM-OH) dendrimer as initiator, followed by the ATRP of GAMA monomer. The degree of crystallization of PCL block within copolymers decreased with the increasing block length ratio of outer PGAMA to inner PCL. Moreover, the morphology of self-assembled aggregates could be conveniently transformed by the weight fraction of hydrophilic PGAMA block, which changed from large compound micelles to vesicles. The in vitro degradation of PAMAM-PCL-PGAMAs was compared with liner LPCL-PGAMAs. The results show the enzymatic degradation rate increased with increasing content of hydrophilic PGAMA, the degradation rate of PAMAM-PCL-PGAMA was faster than LPCL-PGAMA. Nimodipine drug was loaded within both PAMAM-PCL-PGAMA and LPCL-PGAMA, and it was found that both the drug-loading capacity and drug-loading efficiency of PAMAM-PCL-PGAMA were higher than those of LPCL-PGAMA. The in vitro drug release rate of LPCL-PGAMA was faster than that of PAMAM-PCL-PGAMA in aqueous solution at 37℃.(5) Synthesis and characterization, of amphiphilic Star-Shaped Porphyrin-Cored poly(L-Lactide)-b-poly(gluconamidoethyl methacrylate) block copolymersStar-shaped porphyrin-cored poly(L-Lactide) (SPPLA) was synthesized using a tetra-hydroxyethyl terminated porphyrin as a core initiator and DMAP as a catalyst in THF at 50℃. The molecular weight of as-synthesized polymer could be adjusted linearly by controlling the molar ratio of L-LA to porphyrin core initiator, and the molecular weight distribution was reasonably narrow. Then, using SPPLA-BSPA as the macroRAFT agent, amphiphilic star-shaped porphyrin-cored poly(L-Lactide)-b-poly(gluconamidoethyl methacrylate) block copolymers (SPPLA-PGAMA) were synthesized from reversible addition-fragmentation chain transfer polymerization (RAFT) of unprotected GAMA glycomonomer in NMP solution at 70℃. The block length of glycopolymer within as-synthesized SPPLA-PGAMA copolymers could be adjusted by controlling the molar ratio of GAMA glycomonomer to SPPLA-BSPA macroRAFT. The degree of crystallization of PLLA block within copolymers decreased with the increasing block length ratio of outer PGAMA to inner PLLA. Moreover, the fluorescent property of porphyrin core was retained within these copolymers.