Towards developing surface eroding poly(alpha-hydroxy acids).

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.