Synthesis Of Degradable Poly (Lactic Acid) Copolymers By Direct Polycondensation

Polylactic acid (or Polylactide) (PLA) which was widely used in many field because of its biodegradable and biocompatible properties, have gained enormous attention recently. However, onefold structure and properties limits the applications of PLA homopolymer. The most common strategy to overcome this difficulty is to prepared the copolymers. A wide range of biodegradable copolymers matrices were described in this review with a special emphasis on polylactide because of more eco-friendliness from its origin as contrast to the fully petroleum-based polymers and control of carbon dioxide balance after their composting. Lactic acid (or lactide) copolymerized with hydroxyl acid, amino acid or polymers such as poly(ethylene glycol), starch, etc., can obviously improve the strength, toughness, hydrophilic and controlled-degradable properties of PLA, in the same time, can obtain the linear, comb-like, star-like or cross-linked copolymers. These materials are attracting considerable interest in materials science research. This review aims at highlighting on recent developments in preparation of biodegradable linear, comb-like, star-like or cross-linked PLA copolymers and the catalysts (system) using in copolymerization.The thesis consists of main contents as followings:Poly(lactic acid-glycolic acid) was synthesized from lactic acid and glycolic acid by direct polycondensation using various catalysts in the absence of organic solvents at 170oC. The effect of catalyst and its dosage on molecular weight and yield of PLGA was investigated. As a result, the sulfuric acid (98%), p-toluenesulfonic acid is best. At the same time, the phthalic anhydride is best when it mix with SnCl2·2H2O, ZnCl2, FeCl3 and ZnO, respectively. The phosphorous acid, succinic anhydride and sulfuric acid (98%) also have a good catalytic effect. The PLGA with different viscosity-average molecular weight were characterized by gel permeation chromatography (GPC), the results showed that the copolymer does not contain small molecular compounds, and its molecular weight distribution was narrower. The structure PLGA was confirmed by Nuclear magnetic resonance spectroscopy (NMR). The data of thermogravimetric analysis (TG) showed that the thermal stability of PLGA increased slightly with increasing its molecular weight. The products were suitable for controlled release drug coated materials.A series of multi-hydroxyl (2, 4 and 8) terminated poly(ethylene glycol)s and their biodegradable, bio-compatible, branched barbell-like (PLGA)n-b-PEG-b-(PLGA)n (n=1, 2, 4) copolymers have been synthesized. The lengths of the PLGA arms were varied by controlling the molar ratio of monomers to hydroxyl groups of PEG ([LA+GA]0/[–OH]0=23, 45, 90). Chemical structures of synthesized barbell-like copolymers were confirmed by both 1H and 13C-NMR spectroscopy. Molecular weights were determined by 1H-NMR end-group analysis and gel permeation chromatography (GPC). The result of hydrolytic degradation indicated that the rate of degradation increased with the increase of arm numbers or with the decrease of arm lengths. The thermal properties were evaluated by using differential scanning calorimetry (DSC) and a thermogravimetric analysis (TGA). The results indicated that the thermal properties of barbell-like copolymers depended on the structural variations. The morphology of (PLGA)n-PEG-(PLGA)n copolymers self-assembly films were investigated by atomic force microscope (AFM), the results indicated that the microphase separation existed in (PLGA)n-PEG-(PLGA)n copolymers.A series of biodegradable poly(ethylene glycol)-supported poly(lactic-ran-glycolic acid) (PLGA) linear-hyperbranched barbell-like copolymers were synthesized with poly(ethylene glycol) (PEG), D,L-lactic acid (D, L-LA) aqueous solution, glycolic acid (GA) and gluconic acid (Glu) under bulk condition. The branching density of the hyperbranched section were varied by controlling the molar ratio of gluconic acid to hydroxyl-terminal groups of PEG ([Glu]/[OH]=1, 3.5, 6.0, 8.5). Chemical structures of the copolymers were confirmed by both 1H and 13C-NMR spectroscopy. The molecular weights were determined by 1H-NMR group analysis and gel permeation chromatography (GPC), respectively, and group analysis gave reasonably consistent values. The results of hydrolytic degradation indicated that these copolymers degraded completely not more than three weeks. The thermal properties were evaluated using differential scanning calorimetry (DSC) and by performing a thermogravimetric analysis (TGA). The result indicated that the glass transition temperature (Tg) and melting temperature (Tm) of these copolymers not more than 50°C. The self-assembly behavior of these copolymers on hydrophilic surface was investigated. The morphology of these linear-hyperbranched barbell-like copolymers self-assembly films were investigated by atomic force microscope (AFM), the results indicated that these copolymers could exhibit a more nonhomogeneous, more rough structural orientation films on silicon wafer substrate with increasing the branching densities.High molecular weight poly(lactic acid-glycolic acid-ε-caprolactam) (PLGC) copolymer was synthesized by simply heating a mixture of DL-lactic acid aqueous, glycolic acid andε-caprolactam using organic anhydride and tin (II) chloride dihydrate (SnCl2·2H2O) or metal powder as catalyst without organic solvents. At the same time, in order to investigate the effects of the structure of amino acid on the properties of copolymers, poly(lactic acid-glycolic acid-glycine), poly(lactic acid-glycolic acid-L-alanine), poly(lactic acid-glycolic acid-β-alanine), poly(lactic acid-glycolic acid-γ-aminobutyric acid), poly(lactic acid-glycolic acid-L-phenylalanine) were synthesized under the same conditions, respectively. The structure of PLGC was confirmed by FT-IR and NMR spectra. The average molecular weights of PLGC were determined by Ubbelohde model (corrected by 1H-NMR end-group analysis). The results indicated that compounds of organic anhydride and SnCl2·2H2O were active, and the highest average molecular weights could achieve 9800Da. The thermal properties were evaluated using differential scanning calorimetry (DSC), the results indicated that the glassy-transition temperatures (Tg) of polyesteramide increased with increasing the carbon atom numbers between carboxyl and amino-group of amino acid, also the glassy-transition temperatures (Tg) was higher whenα-carbon atom of amino acid linked with a"rigid"group compared with a"soft"group. The solubility and hydrolytic degradation of PLGC copolymers were investigated.poly(glutamic acid-co-lactic acid-co-glycolic acid) (PGLG), an amphiphilic biodegradable copolymer, was synthesized by simply heating a mixture of L-glutamic acid (Glu), DL-lactic acid and glycolic acid with the present of stannous chloride. The unique branched architecture comprising of glutarimide unit, polyester unit and polyamide unit was confirmed by NMR spectrum. The PGLG was soluble in many organic solvents and aqueous solution of sodium hydroxide (pH≧9.0). The thermal properties were evaluated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Molecular weights were determined by 1H-NMR end-group analysis and GPC respectively, and the results indicated that the higher Glu content resulted in a decrease of the molecular weight.poly(L-tyrosine-co-lactic acid-co-glycolic acid) (PTLG), an amphiphilic biodegradable polymer, was synthesized by simply heating a mixture of L-tyrosine (Tyr), DL-lactic acid and glycolic acid in the present of stannous chloride. The linear architecture comprising of polyester unit and polyamide unit and hydroxybenzene side-group was confirmed by NMR spectrum. The PTLG was soluble in many organic solvents and aqueous solution of sodium hydroxide (pH≧9.0). The thermal properties were evaluated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Molecular weights were determined by 1H-NMR end-group analysis and GPC.Starch graft biodegradable poly(lactic acid-co-glycolic acid) (St-g-PLGA) and poly(lactic acid-co-glycolic acid-co-ε-caprolactam) (St-g-PLGC) copolymers were prepared by direct polycondensation from soluble starch, lactic acid, glycolic acid and caprolactam in presence of stannous chloride (SnCl2·2H2O). The chemical microstructure of the resultant copolymers was clarified by NMR spectroscopy and the thermal properties were investigated by differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis. Moreover, the mechanical properties, solubility and degradation velocity were measured. The results indicated that the glassy-transition temperature (Tg) increased with decreasing the contents ofε-caprolactam. The mechanical properties examination demonstrated that the tensile strength and bending strength changed from 32.3Mpa and 69Mpa to 24.2Mpa and 28Mpa with increasing the contents ofε-caprolactam, respectively. The solubility test shown that the copolymers could dissolved in some organic solvents. Because of the poly(ε-caprolactam) is not biodegradable, the rate of degradation of starch-graft-poly(lactic acid-co-glycolic acid-co-ε-caprolactam) copolymers were much slower than that of starch-graft-poly(lactic acid-co-glycolic acid) copolymers.The novel biodegradable polylactic acid-β-cyclodextrin (PLA-β-CD) copolymeric cross-linked microgels were prepared by the radical copolymerization of PLA macromonomer and polymerizableβ-CD derivatives, which theβ-CD derivatives with various numbers of polymerizable vinyl groups were synthesized by 1-allyloxy-2,3-epoxy propane (AGE) andβ-CD. The chemical structures of polymerizable monomers were measured by NMR. The thermal properties, size, morphology, in vitro degradation and swelling behavior of the microgels were investigated. The results indicated that the microgels were stable under thermal condition up to 200°C. The microgels were spherical in aqueous solution. The hydrophilicity of the microgels increased with increasing ofβ-CD contents, while the swelling ratios and rate of degradation decreased. The more vinyl groups onβ-CD the higher cross-linked density, which resulted in a decrease of the swelling ratios and the rate of degradation.