Xu Xiao-Jun, Sy Jay C, Prasad Shastri V
Department of Materials Science and Engineering, University of Pennsylvania, 3231 Walnut Street, Philadelphia, Pennsylvania 19104, USA.
Biomaterials. 2006 May;27(15):3021-30. doi: 10.1016/j.biomaterials.2005.12.006.
We have prepared a library of biodegradable polyesters derived from poly(alpha-hydroxy acids) (PHAs) that appear to primarily exhibit surface erosion behavior. This was achieved by increasing the hydrophobicity of the polymers in two distinct steps, namely: macromer formation and a coupling step. In the first step, macromerdiols (MDs) with varying lipophilicities were prepared by polymerization of L-lactide or mixture of L-lactide and glycolide (3/1 by mole) to various lengths (n = 10, 20, 30, and 40) using alkanediols of increasing C-chain length (C6, C8, and C12) as initiators in the presence of Tin(II) catalyst. In the second step, the macromer diols were linked together with diacid dichlorides of varying C-chain lengths (C6, C8, C10, and C12) to yield polyesters ranging in molecular weight (Mw) from 20 to 130 KDa and polydispersity of 1.5-6. These polyesters exhibited different thermal behavior from pure PHAs that can be tuned by changing the initiator core, the lactide/glycolide chain length, and diacid dichloride type. In addition, all these polymers showed solubility in tetrahydrofuran unlike poly(L-lactic acid) (PLLA) and poly(lactide-co-glycolide) (PLGA). In contrast to PLLA and PLGA, the degradation behavior of these novel polyesters exhibited linear profiles consistent with a surface erosion behavior. Release studies using Congo red as a model drug from microspheres prepared from these polyesters showed linear release profiles with correlation constants of least-square fits approaching a value of unity. Degradable polyesters with tunable thermal and degradation behavior may find applications in drug delivery and tissue engineering, where control over these parameters is critical to ensure predictable outcomes.
我们制备了一个由聚（α-羟基酸）（PHA）衍生的可生物降解聚酯库，这些聚酯似乎主要表现出表面侵蚀行为。这是通过两个不同步骤提高聚合物的疏水性来实现的，即：大分子单体形成和偶联步骤。在第一步中，使用碳链长度增加的链烷二醇（C6、C8和C12）作为引发剂，在二价锡催化剂存在下，将L-丙交酯或L-丙交酯与乙交酯的混合物（摩尔比3/1）聚合至不同长度（n = 10、20、30和40），制备出具有不同亲脂性的大分子二醇（MDs）。在第二步中，将大分子二醇与不同碳链长度（C6、C8、C10和C12）的二酰氯连接在一起，得到分子量（Mw）在20至130 kDa之间、多分散性为1.5 - 6的聚酯。这些聚酯表现出与纯PHA不同的热行为，可通过改变引发剂核心、丙交酯/乙交酯链长度和二酰氯类型来调节。此外，与聚（L-乳酸）（PLLA）和聚（丙交酯-共-乙交酯）（PLGA）不同，所有这些聚合物在四氢呋喃中均表现出溶解性。与PLLA和PLGA相比，这些新型聚酯的降解行为呈现出与表面侵蚀行为一致的线性特征。使用刚果红作为模型药物从由这些聚酯制备的微球进行的释放研究显示，线性释放特征的最小二乘拟合相关常数接近1。具有可调节热行为和降解行为的可降解聚酯可能在药物递送和组织工程中找到应用，在这些领域中，对这些参数的控制对于确保可预测的结果至关重要。
