Preparation of drug‐loaded microspheres of linear and star‐shaped poly(D,L‐lactide)s and their drug release behaviors

Linear (1‐arm) and star‐shaped (4‐, 6‐, and 16‐arm) poly(D,L ‐lactide)s (PDLLs) were synthesized by ring‐opening polymerization in bulk of D,L ‐lactide monomer. Hydroxyl end‐group compounds and stannous octoate were used as the initiator and catalyst, respectively. The intrinsic viscosity and glass transition temperature (T_g) of the PDLLs decreased steadily as the branch arm number increased for similar molecular weights. However, the intrinsic viscosity and T_g values of the linear PDLL were less than the star‐shaped PDLL for similar each PDLL arm lengths. Ibuprofen, a poorly water soluble model drug was entrapped in the PDLL microspheres. All drug‐loaded PDLL microspheres were prepared by the oil‐in‐water emulsion solvent evaporation method, were spherical in shape, and had a smooth surface with fine dispersibility. In vitro drug release behaviors indicated that the drug release from the microspheres with higher branch arm number was faster than from those with lower branch arm number. Moreover, the drug release from the star‐shaped PDLL microspheres was slower than that of the linear PDLL microspheres for similar PDLL arm lengths. The drug release behavior could be adjusted through both the branch arm number and arm length of PDLL. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Injectable and Crosslinkable PLGA‐Based Microribbons as 3D Macroporous Stem Cell Niche

Poly(lactide‐co‐glycolide) (PLGA) has been widely used as a tissue engineering scaffold. However, conventional PLGA scaffolds are not injectable, and do not support direct cell encapsulation, leading to poor cell distribution in 3D. Here, a method for fabricating injectable and intercrosslinkable PLGA microribbon‐based macroporous scaffolds as 3D stem cell niche is reported. PLGA is first fabricated into microribbon‐shape building blocks with tunable width using microcontact printing, then coated with fibrinogen to enhance solubility and injectability using aqueous solution. Upon mixing with thrombin, firbornogen‐coated PLGA microribbons can intercrosslink into 3D scaffolds. When subject to cyclic compression, PLGA microribbon scaffolds exhibit great shock‐absorbing capacity and return to their original shape, while conventional PLGA scaffolds exhibit permanent deformation after one cycle. Using human mesenchymal stem cells (hMSCs) as a model cell type, it is demonstrated that PLGA μRB scaffolds support homogeneous cell encapsulation, and robust cell spreading and proliferation in 3D. After 28 days of culture in osteogenic medium, hMSC‐seeded PLGA μRB scaffolds exhibit an increase in compressive modulus and robust bone formation as shown by staining of alkaline phosphatase, mineralization, and collagen. Together, the results validate PLGA μRBs as a promising injectable, macroporous, non‐hydrogel‐based scaffold for cell delivery and tissue regeneration applications.     

生物降解材料聚乳酸的共聚改性研究进展

概述了生物降解材料聚乳酸的物理机械性能和生物性能,指出对聚乳酸进行改性的必要性及常用方法,其中共聚改性方法是最有效的途径之一.综述了聚乳酸与聚乙醇酸、聚己内酯、聚乙二醇、聚氨基酸等的共聚方法、共聚物的性能及其应用.经共聚改性后聚乳酸的力学性能、亲水性能或反应功能性能可以得到改善,降解周期可实现调控,从而满足在生物医学及环保方面的应用需求.     

丙交酯的合成与纯化研究

讨论了丙交酯制备过程中的影响因素，用重结晶法得到了高纯度的丙交酯，并通过熔点、红外光谱和氢核磁共振谱对丙交酯进行了表征。     

Crystallization behavior of biodegradable amphiphilic poly(ethylene glycol)‐poly(L‐lactide) block copolymers

Poly(ethylene glycol)‐poly(L ‐lactide) diblock and triblock copolymers were prepared by ring‐opening polymerization of L ‐lactide with poly(ethylene glycol) methyl ether or with poly(ethylene glycol) in the presence of stannous octoate. Molecular weight, thermal properties, and crystalline structure of block copolymers were analyzed by ¹H‐NMR, FTIR, GPC, DSC, and wide‐angle X‐ray diffraction (WAXD). The composition of the block copolymer was found to be comparable to those of the reactants. Each block of the PEG–PLLA copolymer was phase separated at room temperature, as determined by DSC and WAXD. For the asymmetric block copolymers, the crystallization of one block influenced much the crystalline structure of the other block that was chemically connected to it. Time‐resolved WAXD analyses also showed the crystallization of the PLLA block became retarded due to the presence of the PEG block. According to the biodegradability test using the activated sludge, PEG–PLLA block copolymer degraded much faster than PLLA homopolymers of the same molecular weight. © 1999 John Wiley amp; Sons, Inc. J Appl Polym Sci 72: 341–348, 1999     

Blends of crystalline and amorphous poly(lactide). III. Hydrolysis of solution-cast blend films

Hydrolysis of blend films prepared from amorphous poly(DL-lactide) (a-PLA) and isotactic crystalline poly(D- or L-lactide) (c-PLA) having different c-PLA contents [X = c-PLA/(a-PLA + c-PLA)] was performed in phosphate buffered solution of pH 7.4 at 37°C. The blend films before and after hydrolysis were studied using gel permeation chromatography, tensile testing, differential scanning calorimetry (DSC), and optical rotation. The mass of the blend films remaining after hydrolysis of longer than 20 months was larger with the increasing initial X. The tensile strength of the blend films remained unchanged in the early stage of hydrolysis, followed by a rapid decrease with time, the duration of period for the tensile strength remaining unchanged was longer for the blend films of smaller X. The change in crystallinity, molecular weight, and specific optical rotation during hydrolysis of the blend films revealed that degradation took place preferentially in the amorphous region than in the crystalline region of the blend films. A double melting peak was observed in the DSC spectra of blend films with X = 0.75 and 0.5 after hydrolysis for 20 months. The time difference in the induction of reduction between the tensile strength and the mass due to hydrolysis of the blend films increased with an increase in X. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 63: 855–863, 1997     

Properties and Biodegradability of Polymer Blends of Poly(L‐lactide)s with Different Optical Purity of the Lactate Units

Polylactides with high and low L ‐isomeric ratios of the lactate units (PLA99.0 and 77.0, where the numbers correspond to the L ‐ratios) were melt‐blended to analyze the changes in properties and biodegradability with the polymer blend. The crystallinity of the blends was almost similar to that of the blends of PLLA and PDLLA. The glass transition behavior supported the compatibility of both polymers. The glass transition behavior was indicative of a compatible nature of both polymers. The tensile modulus of the blends was almost identical irrespectively of the blend ratio, while their tensile strength decreased with decreasing composition of PLA99.0. Above T_g, the storage modulus of the blends dropped from 2–3×10⁹ Pa to 1–3×10⁶ Pa and then increased to a different level depending on the crystalline nature of the blends. The biodegradability of the blends increased with decreasing composition of PLA99.0. This difference in degradability can be well explained by our random packing model of local helices of the L ‐sequenced chains for the L ‐rich PLA samples.     

聚乳酸在生物医学领域中的应用

简要介绍高分子量聚乳酸的合成方法、良好的生物相容性、可吸收性及生物降解性。通过概述聚乳酸在药物释放材料、眼科材料、外科手术缝合线、骨折内固定材料以及组织工程修复等方面的应用,对其在生物医学领域的研究前景作了进一步展望。     

无需高真空度的D,L-丙交酯合成工艺

在水喷射泵容易达到的—0.095MPa～0.098MPa表压真空度合成D,L-丙交酯,用硫酸亚锡等催化剂,以工业级D,L-乳酸为原料,粗产物产率最高为理论产率的94％,与以前的方法相差很少,但工艺条件难度大大降低。丙交酯结晶母液也可再用于制备丙交酯。还讨论了内消旋丙交酯的存在对D,L—丙交酯产率的影响。     

Poly(L‐lactide): v. effects of storage in swelling solvents on physical properties and structure of poly(L‐lactide)

The effects of storage at 25°C in swelling solvents having different solubility parameter (δ_s) values of 16.8–26.0 J^0.5 cm^−1.5 on the physical properties and structure of as‐cast poly(L ‐lactide) (PLLA) films was investigated by the degree of swelling (DS), differential scanning calorimetry (DSC), and tensile tests. It was found that PLLA film shows durabity to swelling solvents having δ_s values much lower or higher than the value range of 19–20.5 J^0.5 cm^−1.5 and that the polymer solubility parameter (δ_p) for PLLA is in the value range of 19–20.5 J^0.5 cm^−1.5. The decrease in the glass transition temperature (T_g) and tensile properties and the increase in melting temperature (T_m) and crystallinity (x_c) were larger for PLLA films swollen in solvents having a high DS at 7 days (DS_7days). The slight increase in T_m and x_c for PLLA films after swelling in solvents with high DS_7days values was due to the crystallization of PLLA that occurred during swelling, while the small increase in T_g and elongation at break (ε_B) for PLLA films after immersion in the solvents having low DS_7days values was ascribed to stabilized chain packing in the amorphous region. The T_g, ε_B, and Young's modulus of the PLLA films after swelling in the solvents varied in the ranges of 47–57°C, 4–8%, and 55–77 kg/mm², depending on their DS_7days or δ_s values. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 1582–1589, 2001