Synthesis and Erosion Properties of PEG-Containing Polyanhydrides Sijian Hou, Laurie K. McCauley, Peter X. Ma * Introduction Parathyroid hormone (PTH) is a peptide hormone that can exhibit either anabolic or catabolic actions in bone, depending on the dosage and delivery pattern. [1] A continuous high-dose delivery of PTH leads to a catabolic effect, while a continuous low-dose or a pulsatile high- dose delivery of PTH results in an anabolic effect in bone. The high pulsatile dose is considered strongly anabolic and valuable for clinical application. Although daily injection is a feasible anabolic treatment, it is not a convenient mode of administration and is not a favorable choice of patients. Therefore controlled delivery of PTH in an anabolic fashion is highly desirable. Biodegradable polymers have been widely pursued for controlled releases of therapeutics. [2–6] We previously explored the possibility of using biodegradable polymers to protect the bioactivity of PTH for controlled release formulations. [7] In that study, we demonstrated that biodegradable poly[(lactic acid)-co-(glycolic acid)] (PLGA) microspheres could be used to encapsulate PTH to protect the PTH from denaturing and to control the delivery duration through the variation of polymer structure. However, due to the bulk erosion nature of PLGA pulsatile Full Paper To tailor the erosion rate of polyanhydrides while retaining their surface erosion character- istics, new three-component polyanhydrides of sebacic acid, 1,3-bis( p-carboxyphen- oxy)propane and poly(ethylene glycol) were synthesized. The hydrophilicity of the polymer increased and its mechanical strength decreased with increasing PEG content. Correspondingly, the erosion rate increases with increasing PEG content, whereas it decreases with increasing specimen thickness. This indicates that the incorporation of poly(ethylene glycol) into traditional two- component polyanhydrides retains their surface erosion properties while making the erosion rate tunable. The new polyanhydrides hold potential for drug delivery applications. S. Hou, P. X. Ma Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA Fax: þ1 734 647 2110; E-mail: mapx@umich.edu L. K. McCauley Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI 48109, USA L. K. McCauley Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA P. X. Ma Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA P. X. Ma Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA 620 Macromol. Biosci. 2007, 7, 620–628 ß 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/mabi.200600256