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Doxil macrophages

Kentaro Nishida, Misaki Kashiwagi, Shunsuke Shiba, Kiwamu Muroki, Akihiro Ohishi, Yusuke Doi, Hidenori Ando, Tatsuhiro Ishida, Kazuki Nagasawa
Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil® , Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP...
December 15, 2017: Toxicology and Applied Pharmacology
Azar Shokri, Javad Akhtari, Masoud Keighobadi, Mahdi Fakhar, Saeed Hosseini Teshnizi, Saeed Emami, Sajede Sadjjadian
OBJECTIVE: To evaluate the effect of doxorubicin and its pegylated liposomal formulation (Doxil, Caelyx) on in vitro susceptibility of promastigote and amastigote stages of Leishmania major. METHODS: Throughout in vitro assays the IC50 was calculated in the promastigotes and amastigotes forms in J774 macrophage cell line. Also as cytotoxicity in J774 cell line macrophages. RESULTS: Doxorubicin and Doxil showed the same activity against promastigote form with IC50 values of 10...
June 2017: Asian Pacific Journal of Tropical Medicine
Mary Rusckowski, Yuzhen Wang, Francis G Blankenberg, Zoia Levashova, Marina V Backer, Joseph M Backer
BACKGROUND: scVEGF/(177)Lu is a novel radiopharmaceutical targeted by recombinant single-chain (sc) derivative of vascular endothelial growth factor (VEGF) that binds to and is internalized by vascular endothelial growth factor receptors (VEGFR). scVEGF/(177)Lu potential as adjuvant and neoadjuvant anti-angiogenic therapy was assessed in metastatic and orthotopic mouse models of triple-negative breast cancer. METHODS: Metastatic lesions in Balb/c mice were established by intracardiac injection of luciferase-expressing 4T1luc mouse breast carcinoma cells...
December 2016: EJNMMI Research
Yoshiyuki Hattori, Kazuhiko Shibuya, Kaori Kojima, Andang Miatmoko, Kumi Kawano, Kei-Ichi Ozaki, Etsuo Yonemochi
Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed...
July 2015: International Journal of Oncology
Ciara Kelly, Ciaran Lawlor, Colin Burke, James W Barlow, Joanne M Ramsey, Caroline Jefferies, Sally-Ann Cryan
Abstract Carriers are often an essential element of drug delivery, bestowing attributes to their cargo such as biocompatibility, enhanced delivery, extended half-life and efficacy as well as mediating specific targeting at a tissue, cell or intracellular level. Liposomes and lipid-based carriers have been investigated for decades for this purpose, many achieving clinical approval including products such as Doxil® and Myocet™. Large-scale compound screens are routinely carried out in the field of drug discovery; however, less work has been done on harnessing high-throughput methods for carrier material screening...
December 30, 2014: Journal of Liposome Research
Nicolas Bertrand, Jun Wu, Xiaoyang Xu, Nazila Kamaly, Omid C Farokhzad
Cancer nanotherapeutics are progressing at a steady rate; research and development in the field has experienced an exponential growth since early 2000's. The path to the commercialization of oncology drugs is long and carries significant risk; however, there is considerable excitement that nanoparticle technologies may contribute to the success of cancer drug development. The pace at which pharmaceutical companies have formed partnerships to use proprietary nanoparticle technologies has considerably accelerated...
February 2014: Advanced Drug Delivery Reviews
János Szebeni, Péter Bedőcs, Domokos Csukás, László Rosivall, Rolf Bünger, Rudolf Urbanics
Intravenous administration of low (milligram) doses of nanoparticulate materials in pigs can lead to acute cardiopulmonary, hemodynamic, hematological, biochemical and dermatological changes within minutes, mimicking the human infusion (or anaphylactoid) reactions to many state-of-the-art (nano)medicines and biologicals. Because of the causal role of complement (C) activation, the phenomenon was called C activation-related pseudoallergy (CARPA). This review summarizes the available information on porcine CARPA caused by different liposomes and polymers...
December 2012: Advanced Drug Delivery Reviews
Donna A Volpe, Arthur B Shaw, Xiao-Hong Chen, Liang Zhou, Mei-Ling Chen
The aim of this study was to evaluate whether temperature stress conditions affect the cellular uptake of liposomal doxorubicin, Doxil (DXL; Ortho Biotech, Raritan, New Jersey, USA), and liposomal daunorubicin, DaunoXome (DXM; Gilead Sciences, San Dimas, California, USA). Uptake of these cytotoxic compounds is essential for their pharmacological effect. Commercially available DXL and DXM were stressed for 6 days under altered temperature conditions of 22 and 50 degrees C, as compared to storage in their buffered formulations at the labeled temperature of 4 degrees C...
June 2010: Journal of Liposome Research
Manuela Banciu, Raymond M Schiffelers, Gert Storm
PURPOSE: Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCL-encapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated cytotoxicity towards tumor cells. METHODS: The antitumor activity of Doxil was evaluated in B16...
August 2008: Pharmaceutical Research
Alberto Gabizon, Dinah Tzemach, Lidia Mak, Moshe Bronstein, Aviva T Horowitz
Stealth (pegylated) liposomal doxorubicin (Doxil) has been extensively studied at the pre-clinical and clinical level in recent years. However, one issue not yet addressed is the effect of dose on tumor localization and therapeutic efficacy of Doxil. Although it has been reported that the pharmacokinetics of drug-free Stealth liposomes is independent of dose within a certain range, clinical pharmacokinetic analysis of Doxil suggests a dose-dependent clearance saturation phenomenon when a broad dose range is examined...
November 2002: Journal of Drug Targeting
J W Park, D B Kirpotin, K Hong, R Shalaby, Y Shao, U B Nielsen, J D Marks, D Papahadjopoulos, C C Benz
We have generated anti-HER2 (ErbB2) immunoliposomes (ILs), consisting of long circulating liposomes linked to anti-HER2 monoclonal antibody (MAb) fragments, to provide targeted drug delivery to HER2-overexpressing cells. Immunoliposomes were constructed using a modular strategy in which components were optimized for internalization and intracellular drug delivery. Parameters included choice of antibody construct, antibody density, antibody conjugation procedure, and choice of liposome construct. Anti-HER2 immunoliposomes bound efficiently to and internalized in HER2-overexpressing cells in vitro as determined by fluorescence microscopy, electron microscopy, and quantitative analysis of fluorescent probe delivery...
July 6, 2001: Journal of Controlled Release: Official Journal of the Controlled Release Society
P Laverman, M G Carstens, O C Boerman, E T Dams, W J Oyen, N van Rooijen, F H Corstens, G Storm
Previously, we showed that long-circulating polyethylene glycol (PEG)-liposomes are cleared rapidly from the circulation when injected repeatedly in the same animal. In this article, we describe the effects of PEG-coating, the circulation time, the lipid dose, and the presence of encapsulated doxorubicin on the pharmacokinetics upon repeated injection in rats. Furthermore, the role of liver and splenic macrophages was investigated. Liposomes without PEG-coating also showed the so-called "enhanced clearance effect": blood levels at 4 h post injection decreased from 62...
August 2001: Journal of Pharmacology and Experimental Therapeutics
A A Gabizon
Pegylated liposomal doxorubicin (Doxil, Caelyx) is a formulation of doxorubicin in poly(ethylene glycol)-coated (stealth) liposomes with a prolonged circulation time and unique toxicity profile. We review the preclinical and clinical pharmacology as well as recent clinical data obtained in specific cancer types. Doxil liposomes retain the drug payload during circulation and accumulate preferentially in tissues with increased microvascular permeability, as often is the case of tumors. Doxil toxicity profile is drastically different from that of doxorubicin, and is characterized by dominant and dose-limiting mucocutaneous toxicities, mild myelosuppression, minimal alopecia, and no apparent cardiac toxicity...
2001: Cancer Investigation
K Maruyama
The current status of newly developed polyethyleneglycol coated liposome (PEG-liposome) were described in this review. Liposomes have demonstrated considerable promise as a carrier for the delivery of drugs in vivo. However, one of the drawback is that most liposomes intravenously injected into animals are rapidly removed from the blood circulation by uptake primarily in the cells of reticuloendothelial system (RES). It has been found that PEG-liposome are not readily taken up by the macrophages in the RES and hence stay in the circulation for a relatively long period of time...
March 1998: Nihon Rinsho. Japanese Journal of Clinical Medicine
G Storm, M T ten Kate, P K Working, I A Bakker-Woudenberg
The introduction of long-circulating liposomes sterically stabilized by surface coating with polyethylene glycol has expanded the potential for drug targeting to tumors. In recent clinical studies, evidence of significant antitumor activity has been obtained with the industrially prepared formulation of long-circulating polyethylene glycol-coated liposomes containing doxorubicin, referred to as DOXIL. Previous studies performed in rats showed that doxorubicin-containing liposomes can exert major toxic effects on the liver macrophage population for a considerable period of time; a strong impairment of phagocytic function and even a substantial depletion of the liver macrophage populations were observed...
January 1998: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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