Abstract
OBJECTIVE To prepare 9-nitrocamptothecin self-emulsifying microemulsion and investigate the protection effect of self-emulsifying microemulsion on 9-NC lactone form in vitro and in vivo.METHODS Two types of self-emulsifying microemulsion with Cremophor EL and Tween 80 as emulsifier respectively were prepared (SMEDDS-C and SMEDDS-T). Comparing with 9-NC solution, the protection effects of self-emulsifying microemulsion on 9-NC lactone were evaluated. RESULTS When the two kinds of SMEDDS were diluted with saline during the dilution ratio of 1∶20, the diameters of microemulsions were (30.2± 4.6) and (21.8±4.2) nm, and the potentials were -(2.9±0.7) and -(8.1±0.3) mV for 9-NCME-C and 9-NCME-T, respectively. Microemulsion dramatically decreased the conversion rate of lactone form to carboxylate form and increased lactone form proportion. The AUC0-∞ of lactone form were 23 072.24 μg·min·L-1 for 9-NC SMEDDS-C, 20 676.33 μg·min·L-1 for 9-NC SMEDDS-T and 8 954.97 μg·min·L-1 for 9-NC solution after intravenous administration in rats. CONCLUSION The lactone form of 9-NC was significantly protected by self-emulsifying microemulsion.
Key words
9-nitrocamptothecin /
self-emulsifying microemulsion /
lactone form /
intravenous injection /
pharmacokinetics
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ZHO Shu-xin;Lü Jun-li;ZHNG Jun-lin;JING Jun;WNG Jin-cheng;CUI Zheng;ZHNG Qing.
Protection Effect of Self-Emulsifying Microemulsion on 9-Nitrocamptothecin Lactone Form [J]. Chinese Pharmaceutical Journal, 2008, 43(16): 1243-1247
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References
[1] PANTAZIS P，KOZIELSKI A J，MENDOZA J T，et al. Camptothecin derivatives induce regression of human ovarian carcinomas grown in nude mice anddistinguish between non-tumorigenic and tumorigenic cells in vitro[J] . Int J Cancer，1993，53（5）：863-871.
[2] FFSKIA P S，HERRA A，VERMORKEN J B，et al. Clinical phase II study and pharmacological evaluation of rubitecan in non-pretreated patients with metastatic colorectal cancer-significant effect of food intake on the bioavailability of the oral camptothecin analogue[J] .Eur J Cancer，2002，38（6）： 807-813.
[3] BAKA S，RANSON M，LORIGAN P，et al. A phase II trial with RFS2000 (rubitecan) in patients with advanced non-small cell lung cancer[J] .Eur J Cancer，2005，41（11）：1547-1550.
[4] ULUKAN H ，SWAAN P W. Camptothecins： A review of their chemotherapeutic potential[J] .Drugs，2002，62 (14)： 2039-2057.
[5] CAO Z ，HARRIS N ，KOZIELSKI A ，et al. Alkyl esters of camptothecin and 9-nitrocamptot- hecin：synthesis， in vitro pharmacokinetics ，toxicity ，and antitumor activity[J] . J Med Chem，1998 ，41 (1) ：31-37.
[6] LIU M X，WANG Y M，LUO G A.Development of self-microeum/sifying drug delivery systems[J] .Prog Pharm Sci（药学进展），2006，30（9）：397-403.
[7] ZHANG X N，TANG L H，YANG X Y，et al. Preparation of paclitaxel self-emulsification microemulsion and its pharmacokinetics in rats[J] .Chin J New Drugs Clin Rem（中国新药与临床杂志），2005，24(4)：294-298.
[8] CHEN J，PING Q N，GUO J X，et al. Effect of liposomes ehcapsulation on equilibrtam between lactone and carboxylate forms of 9-nitrocamptothecin in vitro[J] .J Chin Pharm Univ（中国药科大学学报），2005，36 (4) ：316-320.
[9] CHEN J，PING Q N，GUO J X，et al. Pharmacokinetics of lactone，carboxylate and total 9-nitrocamptothecin with different doses and administration routes in rats[J] .Biopharm Drug Dispos，2006，27(2)：53-59.
[10] BURKE T G，MI Z. The structural basis of camptothecin interactions with human serum albumin： impact on drug stability[J] .J Med Chem，1994 ，37 (1) ：40 -46.
[11] GELDERBLOM H，VERWEIJ J，NOOTER K，et al. Cremophor EL： the drawbacks and advantages of vehicle selection for drug formulation[J] .Eur J Cancer，2001，37(13)：1590-1598.
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