Enhanced solubility and intestinal absorption of cisplatin by coating with nano-hydroxyapatite

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• 作者：Ryosuke Miyasaka ; ^{miyasaka@sangi-j.co.jp" class="auth_mail" title="E-mail the corresponding author} ; Keiichiro Kikukawa ; Shuji Sakuma
• 关键词：Cisplatin ; Nano-hydroxyapatite ; Oral administration ; Solubility ; Intestinal absorption
• 刊名：Journal of Drug Delivery Science and Technology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：35
• 期：Complete
• 页码：294-302
• 全文大小：1167 K

文摘

We examined oral administration of the poorly water-soluble anti-cancer drug cisplatin (CDDP), using a novel formulation prepared by coating CDDP with nano-hydroxyapatite (CDDP/HAP formulation). Solubility testing showed that dissolution of CDDP from the formulation after 6 h was about 2.5 times that of untreated CDDP raw material. In single-dose oral administration testing in rats, the blood concentration of CDDP as shown by the area under the blood concentration time curve (AUC(0–24)) in the CDDP/HAP formulation group was about 7 times that in a CDDP group at the same dose and AUC(0–72) values for the CDDP/HAP formulation group were concentration-dependent. The AUC(0–72) value for the formulation group was lower at the same dose but almost 1.5 times higher at double the dose compared with rats treated intravenously with CDDP. Growth inhibition of cancer cells was no less when using the CDDP/HAP formulation than with CDDP, and in Lewis lung carcinoma-inoculated mice, the life span of those treated orally with CDDP/HAP formulation was equivalent to that of mice treated intravenously with CDDP. Our results suggest that the formulation using nano-HAP may provide an oral substitute for intravenous infusion of CDDP in cancer patients, so that patient quality of life may be improved.