Author(s): Tamasi G, Serinelli F, Consumi M, Magnani A, Casolaro M,
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Abstract Piroxicam H(2)PIR (H(2)PIR, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide), [Cu(HPIR)(2)(H(2)O)(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)] (H(2)MEL, 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)] (H(2)ISO, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide), and [Cu(HTEN)(2)(H(2)O)(2)] (H(2)TEN, 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 microg Cu/mg gel/mL, i.e. ca 0.8 microM within 48 h that compares well with the IC(50) 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.
This article was published in J Inorg Biochem
and referenced in Journal of Biomedical Engineering and Medical Devices