Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear enzyme topoisomerase I (topo I) has been recently recognized as the target for the anticancer drug camptothecin (CPT; NSC 94600) and its derivatives. This drug has been reported to display effective antitumor effects on a variety of human tumor models xenografted in nude mice. However clinical studies of sodium CPT have revealed that the open-ring form of the drug is a poor inhibitor of topo I and much less potent antitumor agent than CPT lactone. However, the insolubility of CPT lactone makes it difficult to devise a suitable formulation for further clinical testing. In view of these observations, we report here the successful incorporation of CPT into a liposome-based drug delivery system (LCPT) composed of DPPC:Sph:CHOL:PI (2.4:6.6:1.0:0.05 M ratio) that can be used as a suitable formulation for clinical testing of the drug. Higher incorporation efficiency was observed when the total phospholipids:drug ratio = 40 and the cholesterol content = 1%. Image analysis of the CPT-containing liposomes with freeze-fracture electron microscopy has indicated that CPT significantly increased the interlamellar space of the vesicles as a result of its intercalation between lipid bilayers. This has occurred with no major disruptive effects on the bilayer structure. The in vitro drug release study in human serum was characterized by an initial rapid loss-of 50% of contents during 4 h, followed by a slow leakage of the remaining 50% of the total drug over a 20 h period. When tested for its antitumor activity on nude mice xenografted with human malignant melanoma and breast carcinoma, LCPT displayed effective antitumor activity with minimal host toxicity. For example, single i.m. injection of LCPT at 10 mg/kg has produced complete tumor regression to nude mice xenografted with CLO breast carcinoma. Likewise, similar results were obtained with the nude mice xenografted with human malignant BRO cells melanoma. These results appear to suggest that i.m. administration of liposome-incorporated CPT has considerable potential for the treatment of human neoplastic diseases, especially lymph node metastases.
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PMID:Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts. 775 88

Site-specific delivery of anticancer based therapy of human cancers has led to several remarkable outcomes, particularly in the therapy of breast cancer and lymphoma. Camptothecin, a plant secondary metabolite is widely used in the treatment of metastatic breast cancer and lymphoma. However its side effect profile often results in cessation of therapy. In this study the principle of both active as well as passive targeting using camptothecin loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of camtothecin were prepared by thin film hydration method using a PEGylated phospholipid like DSPE-MPEG 2000. Similarly conventional liposomes were prepared using phospholipids like DPPC, DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. It was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension. Further, chitosan coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. In vivo screening of the formulations for their antitumor efficacy was carried out in rats. Breast cancer was induced in female Sprague-Dawley rats using an indirectly acting chemical carcinogen DMBA (7, 12 dimethyl benz(a)anthracene). It was found that there was significant decrease (P>0.01) in tumor volume in the rat group treated with test 2 formulation and test 1 formulation compared to standard free CPT. However the chitosan coated liposomal formulation showed a better antitumor efficacy than that of the PEGylated liposomal formulation.
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PMID:Preparation and evaluation of lipid vesicles of camptothecin as targeted drug delivery system. 2381 58