Release studies from smart hydrogels as carriers for piroxicam and copper(II)–oxicam complexes as anti-inflammatory and anti-cancer drugs. X-ray structures of new copper(II)–piroxicam an
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- 作者：Gabriella Tamasi ; Federica Serinelli ; Marco Consumi ; Agnese Magnani ; Mario Casolaro ; Renzo Cini
- 关键词：Copper oxicam complexes ; Metal based drugs ; Drug delivery ; Smart hydrogels
- 刊名：Journal of Inorganic Biochemistry
- 出版年：2008
- 出版时间：October 2008
- 年：2008
- 卷：102
- 期：10
- 页码：1862-1873
- 全文大小：1024 K
文摘
Piroxicam H2PIR (H2PIR, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide), [Cu(HPIR)2(H2O)2] previously prepared and tested from this laboratory and at National Institute of Health, National Cancer Institute, Developmental Therapeutic Program, NIH-NCI-DTP, USA [R. Cini, G. Tamasi, S. Defazio, M.B. Hursthouse, J. Inorg. Biochem. 101 (2007) 1140–1152, and references cited therein], [Cu(HMEL)2(DMF)] (H2MEL, 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide; DMF, N,N-dimethylformamide), [Cu(HISO)2] (H2ISO, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide), and [Cu(HTEN)2(H2O)2] (H2TEN, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-thieno[2,3-e][1,2]thiazine-3-carboxamide 1,1-dioxide), were loaded on CMH2 hydrogel (co-1:10-poly(N-methacryloyl-l-histidine-co-N-isopropylacrylamide) cross-linked with N,N′-ethylene-bis-acrylamide (EBA) 2 % ) and the kinetics of release of Cu–HPIR species in several media were studied. The release of Cu(HPIR)2 in DMSO from CMH2 hydrogel after swelling and loading from DMSO followed a diffusion controlled process. The release of Cu(HPIR)/Cu(HPIR)2 from dried CMH2 hydrogel after swelling and loading from THF solution, then soaking into water/DMSO 95:5 v/v (pH 5.6) followed a relaxation controlled and diffusion controlled mechanism. The amount of Cu(HPIR)2 released in the medium reached 0.03 μg Cu/mg gel/mL, i.e. ca 0.8 μM within 48 h that compares well with the IC50 values reported for metal based drugs like carboplatin (diammino(1,1-cyclobutandicarboxylato)platinum(II)) against certain human tumor cell lines. The release studies performed by monitoring both the absorbance values at 362 nm (sensitive to metal-bound HPIR−) and the content of Cu via AAS, showed an excellent agreement with the Cu(HPIR)2 or Cu(HPIR)2 stoichiometry, depending on the delivery medium. Corresponding studies were performed for other Cu(oxicam–H)2 species in different delivery media.