Studies On The Preparation And Degradation Of Polylactide And Its Hydrophilic Copolymers

Polylactide (PLA) and its copolymers are a kind of much better biocompatible and biodegradable polymers, which are being increasingly used in many fields, such as tissue engineering, implantable carries for drug delivery system as well as surgical repair materials, and been accepted by the U.S. Food and Drug Administration (FDA) for internal use in the human body. However, this kind of polymers is still limited in above applications due to its intrinsic hydrophobicity. One of the possible and promising approaches to overcome this problem is to introduce hydrophilic units into the aliphatic polyester to control the hydrophilicity and biodegradability. In this paper, poly (ethylene glycol) (PEG), poly(N-vinylpyrrolidone) (PVP), poly(3-benzyloxy-l, 2-propanediolcyclic carbonate) (PBPC) were introduced to poly(D,L-lactide) (PDLLA) each other, then several kinds of amphiphilic copolymers of PDLLA, such as PDLLA-b-PEG-b-PDLLA, P(BPC-co-DLLA), PDLLA-b-PVP and PVP-b-PDLLA-b-PVP, were synthesized by molecule design in order to modification its properties by introducing functional groups in polylactide.1. PDLLA, whose glass transition temperature was 54.4℃and decomposed temperature 233.86℃, was synthesized from D, L-lactide by bulk ring-opening polymerization with the stannous octoate as catalyst in normal pressure. The results showed that PDLLA was degraded more rapidly in NaOH or HCl solution, and PDLLA with lower molecular weight was degraded more rapidly than that with high molecular weight in the same medium.2. PDLLA-b-PEG-b-PDLLA copolymers were prepared in normal pressure by the ring-opening polymerization of DLLA in the presence of poly (ethylene glycoal) and stannous octoate as initiator. The relationship between the viscosity-average molecular weight of the triblock copolymers, PEG chain length or the molar ratio of lactide to PEG showed the viscosity-average molecular weight of the resulting copolymers increases with the PEG chain length or molar ratio of lactide to PEG. The biodegradation behaviors and hydrophilicity of the copolymers were investigated and the results showed that the contact angle of the copolymers increased with the molar ratio of lactide to PEG, but water uptake and degradability decreased.3. A novel amphiphilic diblock copolymer of PDLLA-b-PVP was synthesized in normal pressure by bulk ring-opening polymerization with the stannous octoate as catalyst, D, L-lactide and hydroxy-terminated poly-N-vinylpyrrolidone (PVP-OH) (Mn=2000) as monomer. Compared with the homo-PDLLA and the diblock copolymer of PDLLA-b-PVP, the copolymer showed higher water uptake, lower contact angle and better hydrophilicity. This meant that the introduction of PVP segments enhanced the surface hydrophilicity of the copolymers.4. A novel amphiphilic block copolymers of PVP and PDLLA, such as PDLLA-b-PVP and PVP-b-PDLLA-b-PVP, were synthesized by atom transfer radical polymerization (ATRP) using N-vinylpyrrolidone as the monomer and polylactide containingα- bromoester group as the macromolecular initiator with CuBr/2,2'-Bipyridine as the catalyst system. (1) Mono-hydroxyl terminated polylactide or double-hydroxyl terminated polylactide (HO-PDLLA-OH) were prepared by bulk melt polycondensation, and subsequently converted to bromine ended PDLLA by the esterification of the resulting macromolecules with 2-bromopropanoyl bromide (PDLLA-Br and Br-PDLLA-Br). The contents of bromine atom in initiators were calculated by analysising hydroxyl number. All the results showed that the content of Br in one mole PDLLA-Br was 0.73mol and that in one mole Br-PDLLA-Br was 1.91mol. (2) It can be seen that the molecular weight of PDLLA-b-PVP and/or PVP-b-PDLLA-b-PVP was increasing with increasing dosage of catalyst and reaction time, raising reaction temperature and increasing mole ratio of monomer to macromolecular initiator. (3) The properties of the copolymers were determined by contact angle and water take-up measurements. The results showed higher water uptake, lower contact angle. It is mean that embedding of the PVP chain can markedly improve surface hydrophilicity of the amphiphilic copolymer. (4) The morphology of the copolymers was measured by transmission electronic microscope (TEM). The results showed that the amphiphilic copolymer can self-assemble into a new morphology with more cores around one shell (polymer micelle). (5) Their degradation behaviors in phosphate buffer solution (pH 7.4), water, NaOH or HCl solution at 37℃were investigated in detail by monitoring the changes in mass during the degradation. The results showed that the target copolymers degraded more rapidly than PDLLA; and the higher of PVP content, the faster the copolymer degraded; degradation of copolymer in NaOH solution was more rapidly than others.5. A novel five-membered cyclic carbonate with hydroxy group being protected (3-benzyloxy-1, 2-propanediolcyclic carbonate, BPC) was synthesized from bis (trichdomethyl) carbonate (BTC) and 3-phenylmethoxymethly-1, 2-propanediol which was easily obtained through the reaction of 3-chloro-1,2-propanediol with sodium phenylmethanolate. Then, P (BPC-co-DLLA) was synthesized in normal pressure by bulk ring-opening polymerization with the stannous octoate as catalyst, DLLA and BPC as monomers. (1) The copolymer was characterized by IR, ~1H-NMR, GPC, DSC and TG. The glass transition temperature of the copolymer ranged between PDLLA's and PBPC's, and decreased with the molar ratio of BPC to DLLA. (2) It can be seen that the molecular weight of P (BPC-co-DLLA) was increasing with decreasing dosage of BPC and increasing reaction time, raising reaction temperature. (3) The results of contact angle and water uptake showed that introduction of OH enhanced the surface hydrophilicity of the deprotected copolymer and increasing with the dosage of BPC. (4) The degradation behavior of protected and deprotected copolymers was investigated in detail in buffer of PBS (pH7.4). The results showed that the deprotected copolymer was degraded more rapidly than protected one; and the higher of BPC content, the faster the copolymer degraded.