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Abstract
9-Nitrocamptothecin (9-NC) is a newly developed but poorly soluble derivative of camptothecin (CPT), which has a wide spectrum of anticancer activity in preclinical evaluation. Lactone moiety is a key structural feature for the antitumor activity of CPT analogs including 9-NC. Lactone stability versus time profiles of 9-NC in vivo following intravenous (i.v.) administration of free and liposomal encapsulated 9-NC has been investigated in this article. After i.v. injection of 9-NC solution, it was found that lactone stability of 9-NC in liver was the poorest in vivo and even worse than that in plasma. In other tissues, lactone stability of 9-NC was better than that in plasma. After liposomal encapsulation, both lactone and total 9-NC concentrations in reticuloendothelial system (RES) tissues, for example, spleen, liver, and lung, were significantly increased. In particular, liposomal encapsulation had a significant improving effect on the lactone stability of 9-NC in the liver. The lactone percentage was increased from 39.11 ± 16.93% to 65.57 ± 9.73% (p < .05) at 10 min and from 30.99 ± 6.54% to 51.22 ± 11.10% (p < .01) at 30 min. On the basis of these results, a theoretical explanation of lactone stability in vivo was discussed. In summary, liposomal encapsulation, which resulted in passive targeting and a significant improvement of lactone stability in the liver, might have clinical utility.