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Synthesis and Characterization of Novel Functional Biodegradable Copolymer Composed of Ricinoleic Acid and L-Lactic Acid

Akio Kishida1, Masaki Ninomiya2, Yuichi Ohya2, Tatsuro Ouchi2, Tsuyoshi Kimura1, and Tsutomu Furuzono3. (1) Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku,, Tokyo, Japan, (2) Faculty of Engineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka, 564-8680, Japan, (3) Department of Bioengineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan

INTRODUCTION Poly(L-lactic acid) (PolyLA; PLA) is one of the most widely used biodegradable and bioabsorbable polymers in the field of biomedical materials. PLA has good biocompatibility, biodegradability, and mechanical properties, however, for developing a novel functional biodegradable polymer, many researches of the introduction of functional groups in the molecular structure of the polymer have been attempted. In this work, we selected ricinoleic acid (RA) as the functional molecule. RA, being the principal constituent of castor oil, is a kind of fatty acid and has an unsaturated bound, a hydroxyl group, and long alkyl side chain. RA is good candidates for preparing biodegradable polymers. MATERIALS AND METHODS Materials. L-lactic acid (90% aqueous solutions) and ricinoleic acid (technically 80% pure) were purchased from Wako Pure Chemical CO. (Tokyo, Japan) and Tokyo Chemical Industry CO. (Tokyo, Japan), respectively, and used without further purification. Benzoyl peroxide (BPO) (70% Remainder Water) was purchased from Aldrich CO. (Milwaukee, WI, USA) and used without purification. All other regents were purchased from Wako Pure Chemical CO. and used as received. Synthesis of Poly(L-lactic acid-r-ricinoleic acid). Random copolymers composed of ricinoleic acid and L-lactic acid were synthesized by direct polycondensation. The reaction yield was calculated from the weight of the dried products and the total mass of LA and RA in feed. A series of copolymers with different composition were prepared by changing ratio of RA to LA in feed. In vitro hydrolytic degradation testing. The copolymers were dissolved in chloroform (4 wt%), and the resulting copolymer solution was deposited onto sample bottles. PLA (Mn = 18500) was used as a reference polymer. After dried in vacuum, the cast films formed on the bottom of the bottle were incubated in 1/15M KH2PO4/ NaHPO4 buffer (pH = 7.0) at 37ēC for 28 days. After 1, 2, 4, 8, 14, and 28 days, the films were washed with distilled water and dried in vacuum at room temperature over night. The molecular weights of the polymers were measured by GPC. The degradation rates were estimated by the molecular weight reduction (%) calculated. Radical reactivity testing. Random Copolymer (RA content = 55 mol%) and BPO were dissolved in chloroform at a concentration of 7.1 × 10-2 wt/vol %. After removal of oxygen, the solution was heated at 45ēC for 5h and 10h. The radical reactivity of random copolymer was evaluated by the change of UV adsorption. RESULTS AND DISCUSSION Synthesis of Poly(L-lactic acid-r-ricinoleic acid). The characterization of the products obtained by the direct polycondensation was done by 1H-NMR, FT-IR, and GPC analysis. The results of FT-IR and 1H-NMR indicate that RA was introduced into the copolymer, and the unsaturated group of the copolymer was preserved through the polycondensation. The GPC elution profiles were unimodal, and the elution profile detected by RI detector was compatible with the one detected by UV detector. This means that the copolymer obtained was not a mixture of the respective homopolymers. From these results, it was confirmed that the polymer prepared here was the poly(L-lactic acid-r-ricinoleic acid) having an unsaturated group in main chain. In vitro hydrolytic degradation testing. The random copolymers showed lower biodegradability as RA content increased. The degradation rate of the copolymer having lower RA content was larger than PLA, while the copolymer having higher RA content degraded slower than PLA. These results suggest that the degradation rate of the copolymer can be controlled by changing not only the crystallinity but also the hydrophobicity due to RA moiety. Radical reactivity testing. As compared with UV adsorption before and after the radical reactivity testing, the adsorption peak arising from double bond at ca. 200nm decreased with an increase in reaction time. This result suggests that the random copolymer has the radical reactivity.