Cancer drug delivery最新文献

{"title":"Studies on tumor necrosis factor (TNF). III. Plasma disappearance curves after intramuscular, subcutaneous, intraperitoneal, and oral administration of human recombinant TNF.","authors":"A Pacini,&nbsp;E Maioli,&nbsp;V Bocci,&nbsp;G P Pessina","doi":"10.1089/cdd.1987.4.17","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.17","url":null,"abstract":"<p><p>Since clinical trials with TNF as a therapeutic agent for cancer are in progress, in this study we have chosen to compare the metabolic characteristics of 125I-labeled and unlabeled RTNF after administration through IM, SC, IP and PO routes. Both RTNF and 125I-RTNF plasma concentration profiles showed an absorption phase and a biexponential decline common to all routes of administration. Moreover the pharmacokinetic analysis indicates that TNF blood levels following SC injection are rather similar to those seen after IM dose. No difference has been found in T max. In contrast, the Kel is apparently increased in the SC route, but the difference is not significant. While a prolonged absorption phase had been obtained after IP injection of RTNF, comparison of t 1/2 beta and Kel between IP and SC or IM route failed to reveal significant differences. Surprisingly some plasma TNF bioactivity has been detected following oral administration.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 1","pages":"17-23"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14728474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of a conjugate of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin in parenchymal and sinusoidal cells of rat liver.","authors":"L Fiume,&nbsp;A Mattioli,&nbsp;G Spinosa","doi":"10.1089/cdd.1987.4.11","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.11","url":null,"abstract":"<p><p>9-beta-D-Arabinofuranosyladenine 5'-monophosphate (ara-AMP) coupled to lactosaminated human albumin (L-HSA), injected i.v. into rats, selectively enters the liver. The conjugate concentration in parenchymal and sinusoidal hepatic cells, isolated by collagenase perfusion, was found to be practically equal in both cell types. This indicates that the high uptake of L-HSA-ara-AMP complex by the whole liver also corresponds to a high conjugate concentration in hepatocytes where ara-AMP should be targeted in order to increase its chemotherapeutic index in chronic hepatitis B treatment.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 1","pages":"11-6"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13585702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microparticulate drug delivery systems as an adjunct to cancer treatment.","authors":"D J Kerr","doi":"10.1089/cdd.1987.4.55","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.55","url":null,"abstract":"<p><p>In an attempt to improve the therapeutic ratio of cytotoxic drugs, which have steep dose-response curves, microparticulate drug delivery systems (MDDS) have been designed for regional administration. Introduction of antineoplastic drug containing microspheres, of appropriate size, into the arterial system of an organ harboring primary or metastatic tumor, will cause tumor infarction by an embolic effect and provide a slow release source of drug trapped within the tumor microvasculature. This review describes recent innovations in synthesis of MDDS and their potential clinical application.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 1","pages":"55-61"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.55","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14429340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of doxorubicin and cisplatin on multicellular tumor spheroids from human lung cancer.","authors":"S Inoue,&nbsp;T Ohnuma,&nbsp;K Takaoka,&nbsp;Y Suzuki,&nbsp;M Kaneko,&nbsp;R Safirstein,&nbsp;J F Holland","doi":"10.1089/cdd.1987.4.213","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.213","url":null,"abstract":"<p><p>We tested the sensitivity to doxorubicin (DXR) and cisplatin (DDP) of multicellular tumor spheroids (MTS) developed from 2 human lung cancer cell lines; PC-10 squamous cell carcinoma and PC-6 small cell carcinoma. DDP was able to maintain its efficacy in MTS: PC-10 MTS were only 3-fold more resistant to DDP than in monolayer and in PC-6 cells DDP induced cell lethality was essentially unchanged irrespective of cells being in a monolayer or MTS. Atomic absorption spectrometry revealed that DDP uptake was essentially identical, irrespective of cells being in monolayer or MTS. DDP's efficient cell kill effects in MTS seems to be explained by its good penetration into the MTS core. In contrast to DDP, these 2 types of cells responded differently to DXR. Thus, PC-10 MTS became progressively more resistant to DXR when their size increased, whereas the susceptibility of PC-6 MTS tended to increase when the MTS grew larger. Fluorescent microscopic study revealed that prominent DXR fluorescence was observed only at the outer layer of PC-10 MTS. In PC-6 MTS, however, DXR fluorescence was diffusely seen in the entire MTS at low concentrations; nevertheless, owing to PC-6 cells' high sensitivity DXR was able to exert cell lethality. The differences in distribution of DXR fluorescence between PC-10 and PC-6 MTS were corroborated by flow cytometric analysis.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 4","pages":"213-24"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14578496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 2 trial of streptozotocin by continuous infusion for metastatic colorectal carcinoma.","authors":"G Clamon,&nbsp;C Riggs,&nbsp;L Stegink,&nbsp;M Traves","doi":"10.1089/cdd.1987.4.43","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.43","url":null,"abstract":"<p><p>Streptozotocin is a nitrosourea with minimal activity against colorectal carcinoma when given by bolus administration. Continuous infusion (CI) streptozotocin has been reportedly less toxic. Twenty-six patients with widely advanced colorectal carcinoma (most heavily pretreated) received 1-3 courses of Streptozotocin by CI to determine efficacy. Two patients (8%) had an objective response. Although CI Streptozotocin is less toxic, it does not have substantial efficacy in colorectal cancer in previously treated patients with widespread metastases.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 1","pages":"43-6"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.43","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14090455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental comparison between hepatic artery infusion and occlusion-infusion of adriamycin.","authors":"K C Wright,&nbsp;S Wallace,&nbsp;R S Benjamin,&nbsp;G D Dodd","doi":"10.1089/cdd.1987.4.33","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.33","url":null,"abstract":"<p><p>Adult mongrel dogs were used to compare hepatic arterial infusion and arterial occlusion-infusion with regard to local and systemic Adriamycin levels. The drug was infused into the right proper hepatic artery of each dog after occlusion of the gastroduodenal artery. Blood and tissue samples were collected at regular intervals for Adriamycin determination. Four weeks later, each dog again received the same agent in the right proper hepatic artery, but this time arterial flow was blocked with an inflated balloon during drug infusion (arterial occlusion-infusion). Blood and tissue drug levels were determined and compared with those obtained using infusion without occlusion. Results indicate that when Adriamycin is administered into the hepatic artery of dogs, occlusion-infusion produces significantly greater hepatic venous drug levels, drug uptake, and drug metabolism than does infusion alone.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 1","pages":"33-41"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14728475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the role of mononuclear phagocytes in the transportation of doxorubicin-containing liposomes into a solid tumor.","authors":"G Storm,&nbsp;H J Van Gessel,&nbsp;P A Steerenberg,&nbsp;P A Speth,&nbsp;F H Roerdink,&nbsp;J Regts,&nbsp;M Van Veen,&nbsp;W H De Jong","doi":"10.1089/cdd.1987.4.89","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.89","url":null,"abstract":"<p><p>The present paper is concerned with the question whether cells of the mononuclear phagocyte system (MPS) function as a transport system for doxorubicin (DXR)-containing liposomes into solid tumors. The investigations were performed in solid IgM immunocytoma bearing Lou/M Wsl rats. In this tumor system macrophage accumulation was observed during DXR and cisplatin induced tumor regression. Tumor-bearing rats were treated i.v. with 1 mg/kg DXR (either free or entrapped in liposomes) for 4 consecutive days. Changes in the cellular composition of the tumor were studied by histology and cytology comparing free and liposomal DXR treatment. Therapy with DXR-liposomes (lip DXR) induced macrophage accumulation similar to free DXR. No differences in cellular changes in the tumor between both types of treatment were found. The DXR-content of tumor-associated cells was measured at various times during treatment with free or lip DXR by means of flow cytometry. Most DXR-fluorescence was associated with dead cells and cellular debris. No clear-cut differences in DXR-content were found between macrophages isolated from tumors of free DXR treated animals and those isolated from lip DXR treated animals. In order to investigate whether DXR-liposomes are taken up by tumor tissue (either via macrophages or directly by the tissue itself), [3H]inulin-labeled DXR-liposomes were administered to tumor-bearing rats. The distribution of radiolabeled lip DXR in non-treated rats was compared with that in rats which were pretreated with non-radiolabeled lip DXR to induce macrophage accumulation. In both untreated and pretreated animals most of the administered 3H-dose was recovered in liver and spleen. Only a minor fraction was recovered from the tumor and other tissues. This fraction was not higher than that obtained when a comparable amount of free [3H]inulin was injected. In conclusion, this study suggests that DXR-liposomes do not enter the solid IgM immunocytoma, even when during therapy macrophages pass the endothelial barrier. Therefore, it is unlikely that macrophage-mediated transportation of DXR-liposomes into the tumor is involved in the mechanism of tumor regression induced by liposome-entrapped DXR.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 2","pages":"89-104"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.89","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14552099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The preparation of large volumes of homogeneous, sterile liposomes containing various lipophilic cytostatic drugs by the use of a capillary dialyzer.","authors":"R A Schwendener","doi":"10.1089/cdd.1986.3.123","DOIUrl":"https://doi.org/10.1089/cdd.1986.3.123","url":null,"abstract":"<p><p>A dialysis method for the preparation of large volumes of stable and homogeneous bilayer liposomes under sterile conditions was developed. The equipment consists of a disposable hemodialysis capillary dialyzer connected to two reservoirs through which the micelle/liposome solution is pumped in a closed circuit. The detergent is removed by a countercurrent flow of the dialysis buffer. Homogeneous, detergent free liposome preparations totaling 100 ml with lipid concentrations ranging from 5 to 25 mg/ml can be prepared within 2-4 hours. Greater lipid concentrations or larger batch volumes can be obtained with dialyzing cartridges allowing for higher detergent clearing performances. The incorporation of lipophilic derivatives of the cytostatic drugs 1-beta-D-arabinofuranosyl cytosine (ara-C) and 5'-fluoro-2'-deoxy uridine (FUdR) is nearly quantitative, and stable, homogeneous bilayer liposomes of about 100 nanometers in diameter are obtained. Liposomes with prodrug concentrations of 2 to 10 mg per milliliter can be prepared depending upon the lipid amounts used. Free ara-C or generally small and water soluble molecules however, cannot be encapsulated within the liposomes due to quantitative loss during dialysis.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"3 2","pages":"123-9"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1986.3.123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14074325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative distribution of free doxorubicin and poly-L-aspartic acid linked doxorubicin in MS-2 sarcoma bearing mice.","authors":"A Mazzoni,&nbsp;R A Gambetta,&nbsp;F Trave,&nbsp;F Zunino","doi":"10.1089/cdd.1986.3.163","DOIUrl":"https://doi.org/10.1089/cdd.1986.3.163","url":null,"abstract":"<p><p>The plasma and tissue distribution of doxorubicin-poly-L-aspartic acid (DX-PAA) and doxorubicin (DX) at equitoxic doses have been studied by a fluorescence assay in tumor bearing mice following administration of a single i.v. bolus injection. A relatively short distribution phase followed by a slow elimination phase characterized the DX-PAA plasma disappearence: at 48 hr after the treatment the conjugate was still detected in plasma. The plasma under the concentration vs. time curve (AUC) of drug equivalents following free DX administration resulted 2.6 times higher than the plasma AUC of free equivalents produced by DX-PAA treatment. In lung, liver and spleen the DX-PAA was accumulated in high concentrations. Low amount of DX equivalents were found in the heart following the conjugate administration: after 2 hr only traces of free anthracycline equivalents were detectable. On the contrary, drug equivalents following free DX treatment remained evaluable in the heart up to 24 hr from the drug administration. No significative differences were observed in the tumor AUC of free DX equivalents produced by free or polymer-linked DX. These data suggest that DX-PAA might act as a depot system slowly releasing the cytotoxic agent. Furthermore the observed accumulation of the conjugate and free DX equivalents in the lung and in the liver suggest a possible therapeutic advantages of DX-PAA in tumors with potential metastasis in these organs.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"3 3","pages":"163-72"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1986.3.163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14897915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct effects of the hypoxic cell sensitizer misonidazole on colony formation in a human tumor cloning assay.","authors":"W Scheithauer,&nbsp;D D Von Hoff,&nbsp;B Forseth,&nbsp;J D Cowan","doi":"10.1089/cdd.1986.3.15","DOIUrl":"https://doi.org/10.1089/cdd.1986.3.15","url":null,"abstract":"<p><p>The human tumor cloning assay as described by Hamburger and Salmon was utilized to study the direct antitumor effects of the hypoxic cell sensitizer misonidazole (MISO). Cells from 106 tumor specimens directly obtained from patients were exposed to MISO at clinically achievable drug concentrations (0.5 mM). Of 30 evaluable tumors, seven specimens (23%) showed a less than or equal to 50% decrease of TCFU's. In vitro sensitivity to MISO was noted in human breast cancer, renal cancer, non small-cell lung cancer, and adenocarcinoma of unknown primary site. A dose response relationship was demonstrated in a subset of experiments including 6 patient's tumors and one human breast cancer cell-line. An analysis relating MISO sensitivity or resistance to the results obtained with other, simultaneously tested standard anticancer drugs indicated that tumors exhibiting a less than or equal to 50% decrease of TCFU's in the presence of MISO were also likely to be sensitive to other cytotoxic drugs. In summary, our data suggest that the 'nitroimidazoles' may exert clinically significant direct antitumor effects in individual tumors. The human tumor cloning assay may have potential to evaluate these direct effects of MISO-analogues and other new radiosensitizers currently being tested in clinical trials.</p>","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"3 1","pages":"15-24"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1986.3.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15069955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}