pubs.acs.org/Macromolecules Published on Web 09/10/2009 r 2009 American Chemical Society Macromolecules 2009, 42, 7285–7291 7285 DOI: 10.1021/ma900747q Novel Biodegradable Poly(ester-ether)s: Copolymers from 1,4-Dioxan- 2-one and D,L-3-Methyl-1,4-dioxan-2-one Yemanlall Lochee, † Archana Bhaw-Luximon, † Dhanjay Jhurry,* ,† and Afksendiyos Kalangos ‡ † Department of Chemistry, Faculty of Science, University of Mauritius, R eduit, Mauritius, and ‡ Department of Cardiovascular Surgery, Geneva University Hospital, Geneva, Switzerland Received April 7, 2009; Revised Manuscript Received September 1, 2009 ABSTRACT: Synthesis of random copolymers by the nonsequential polymerization of 1,4-dioxan-2-one with D,L-3-methyl-1,4-dioxan-2-one was first investigated using a range of classical initiators. Experimental conditions such as temperature and initiator concentrations were varied to achieve reasonable monomer conversions and molar masses. In general, copolymers were slightly enriched in 1,4-dioxan-2-one. On the basis of block lengths of the respective (co)monomer sequences, it is proposed that the copolymer consists of longer blocks of dioxanone units and a pseudoperiodic pattern with a random distribution of MeDX units. The thermal properties of the copolymer changed significantly with the percentage of MeDX units incorporated. A copolymer with 8% mole percent of MeDX units exhibits a T m of 95.5 °C, which is about 15° lower than PDX homopolymer. A range of (PEG) m -b-[(PDX)-co-(PMeDX)] n block copolymers was also successfully prepared using R-methoxy-ω-hydroxy-PEG as macroinitiator. The amphiphilic character of these copolymers is also here demonstrated with spherical core-shell micelles having an average size of 25-30 nm as determined by TEM. The tunable biodegradability characteristics of the hydrophobic core make these polymers interesting candidates as nanocarriers in controlled drug delivery. 1. Introduction Copolymerization offers the possibility to achieve a broader spectrum of chemical, mechanical and biological properties suiting various applications in the field of biomaterials and drug delivery. We review here, in particular, the synthesis of copoly- mers containing poly(ester-ether) units derived from 1,4-dioxan- 2-one as listed in Table 1. It is noteworthy that patents 1-5 dealing with such type of copolymers outnumber, by and large, published articles in this area. A large amount of work covered in patents relates to the random copolymerization of 1,4-dioxanone (DX) with glycolide (GA) or lactide (LA). 2-5 The combination of DX with GA combines the fast absorbing characteristics of PGA with the pliability of PDX while causing a decrease in the crystallinity of the copolymer, thus making it more processable. Raquez et al. 6 first attempted the random copolymerization of DX and ε-caprolactone (CL) but found that the copolymeriza- tion rate was largely in favor of DX incorporation. The resulting copolymer precipitated in toluene due to the insolubility of DX segments. They then successfully prepared PCL-PDX block copolymers via sequential polymerization using Al(O i Pr) 3 as initiator. 6 DX polymerization was shown to be living when initiated by ω-Al alkoxide terminated PCL chains at room temperature. The two blocks were immiscible with each other as confirmed by the presence of two T g s at -65 °C (PCL block) and -10 °C (PDX block). Hong et al. 7,8 substituted partly CL units by trimethylenecar- bonate (TMC) in a block copolymer with a major proportion of DX. The [(PTMC)-co-(PCL)]-b-(PDX) were prepared using the (PTMC)-co-(PCL) unit as macroinitiator in the presence of Sn(Oct) 2 as catalyst. CL units provide low stiffness and excellent handling characteristics while TMC segments bring the required elasticity as they exist in the rubbery state at room temperature. The copolymers exhibited a lower T g compared to PDX. In general, the mechanical properties of [(PTMC)-co-(PCL)]- b-(PDX) were found to be lower than that of PDX due to a decrease in crystallinity except for the knot pull strength which was higher for the copolymer. Dihydroxyterminated PEO of various molar masses have been used as macroinitiator in the presence of Sn(Oct) 2 to copolymer- ize DX. 9-12 The content and length of PEO chains did not affect the thermal properties and crystallization behavior of the triblock (PDX)-b-(PEO)-b-(PDX). The T g and T m values of the copoly- mers varied between -12.7 and -15.2 °C and between 106.6 and 107 °C respectively. Triblock copolymers with PEO central block have also been prepared with outer PDX, PCL or PLA seg- ments. 13-15 All copolymers exhibited a single T g and T m show- ing complete mixing of all segments. Bhattarai et al. 9 showed that random incorporation of PCL units (26-58%) forming a triblock copolymer [(PDX)-co-(PCL)]-b-(PEO)-b-[(PDX)-co- (PCL)] lead to a decrease in both T g (from -23 to -57 °C) and T m (from 100 to 40 °C). The lipase-catalyzed copolymerization of ω-pentadecalactone (DL) with DX has been recently described by Jiang et al. 16 in attempt to obtain metal-free copolymers. The resulting copoly- mer contained nearly random sequences of DL and DX units with a slight tendency toward alternating arrangements. Copo- lymers with a PDL content exceeding 30% showed enhanced thermal stability compared to PDX homopolymer. Finally, the hydrolytic 17 and enzymatic degradation 18,19 of multiblock copolymers consisting of PCL and PDX segments have been studied. In general, the hydrolytic degradation rate increased with increasing PDX content whereas the enzymatic degradation rate decreased. In another paper, 20 we reported on the synthesis and homopolymerization of DL-3-methyl-1,4-dioxan-2-one (DL-3- MeDX) monomer using a range of initiators including FDA *Corresponding author. E-mail: djhurry@uom.ac.mu.