Improvement of Intraperitoneal Chemotherapy for Rat Ovarian Cancer Using Cisplatin‐containing Microspheres

Kumagai, Shogo; Sugiyama, Toru; Nishida, Takashi; Ushijima, Kimio; Yakushiji, M

doi:10.1111/j.1349-7006.1996.tb00238.x

Cited by 12 publications

(8 citation statements)

References 12 publications

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“…However CDDP has severe toxic effects on normal cells of the gut, bone marrow, 4) nerves and the renal tubular epithelium. [20][21][22] To overcome those problems, several platinum-polymer preparations have been investigated, including polylactic acid microcapsules, 23) and microspheres consisting of Llactic acid, 24) dextran, 25) and HPMA copolymer. 26) Most preparations have failed to demonstrate meaningful benefit in vivo.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin‐incorporated Polymeric Micelles Eliminate Nephrotoxicity, While Maintaining Antitumor Activity

Mizumura

Matsumura

Hamaguchi

et al. 2001

Japanese Journal of Cancer Research

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cis-Diamminedichloroplatinum (II) (cisplatin, CDDP), a potent anticancer agent, was bound to the aspartic acid residues of poly(ethylene glycol)-poly(aspartic acid) (PEG-P(ASP)) block copolymer by ligand substitution reaction at the platinum atom of CDDP. The polymeric drug thus obtained was observed to form a micelle structure in aqueous medium, showing excellent water solubility. In the present study, in vitro and in vivo antitumor activity against several human tumor cell lines, toxicity and pharmacokinetic characteristics in rodents of CDDP-incorporated polymeric micelles (CDDP/m) were evaluated in comparison with those of CDDP. In vitro, CDDP/m exhibited 10-17% of the cytotoxicity of CDDP against human tumor cell lines. CDDP/m given by intravenous (i.v.) injection yielded higher and more sustained serum levels than CDDP. In vivo CDDP/m treatment resulted in higher and more sustained levels in tumor tissue than CDDP, and showed similar antitumor activity to CDDP against MKN 45 human gastric cancer xenograft. CDDP/m treatment caused much less renal damage than CDDP. These results indicate that CDDP/m treatment can reduce CDDP-induced nephrotoxicity without compromising the anticancer cytotoxicity of CDDP.Key words: Polymeric micelles -Cisplatin -Nephrotoxicity -EPR effect -DDS cis-Diamminedichloroplatinum (II) (cisplatin, CDDP), the most commonly used anticancer agent, consists of a central platinum atom surrounded by four ligands, two ammonias and two chlorides.1) A high antitumor activity results when the two chloride ligands in CDDP are bi-aquated in aqueous physiological environments; CDDP can then interact directly with DNA and display cytotoxic activity.2, 3) The clinical utility of CDDP is limited by significant general organ toxicity including myelosuppression, 4) ototoxicity, 5) gastrointestinal disturbance, 5, 6) and especially acute nephrotoxicity.7) CDDP, a low-molecularweight compound, is distributed readily into almost all tissues and intracellular compartments. CDDP traverses plasma membranes rapidly via passive diffusion or active transport, and is also rapidly cleared from blood by glomerular excretion, limiting its therapeutic availability. Injection of the maximum permissible amount of this lowmolecular-weight drug to raise its therapeutic concentration and AUC (area under the curve) results in severe toxicity without significantly greater antitumor efficacy. Therefore, several novel forms of controlled release drug delivery have been designed to improve distribution and to prolong the exposure of the tumor to an effective drug concentration.It is known that solid tumors generally possess the following pathophysiological characteristics: hypervascularity, incomplete vascular architecture, secretion of vascular permeability factors, and also the absence of effective lymphatic drainage, preventing the efficient clearance of accumulated macromolecules. These characteristics, unique to solid tumors, are believed to be the basis of the so-called EPR effect (enhanced permeability and retention ef...

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Section: Discussionmentioning

confidence: 99%

Cisplatin‐incorporated Polymeric Micelles Eliminate Nephrotoxicity, While Maintaining Antitumor Activity

Mizumura

Matsumura

Hamaguchi

et al. 2001

Japanese Journal of Cancer Research

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“…However, the possibilities of controlling the NO release can be widened using also other drug delivery systems (DDS), such as microparticles. Microparticles have been used as drug delivery systems because they offer advantages such as a high stability, easy uptake into the cells by endocytosis, and targeting ability to specific tissues or organs by adsorption or coating with ligand materials at the surface of the particles [61][62][63][64][65][66][67]. Many biodegradable polymers are appropriate for making microparticles.…”

Section: Trans-½ruðnoþðnhmentioning

confidence: 99%

trans-[Ru(NO)(NH3)4(py)](BF4)3·H2O encapsulated in PLGA microparticles for delivery of nitric oxide to B16-F10 cells: Cytotoxicity and phototoxicity

Gomes

Barbougli

Espreáfico

et al. 2008

Journal of Inorganic Biochemistry

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“…[47] A monoclonal antibody, MJ01, which recognizes human ovarian cancer antigen CA125 is encapsulated in PLGA microspheres, which is capable of inducing T3 as evidenced by the T-cell proliferation in-vitro, in response to the challenge by CA125. Immunotherapy of ovarian cancer by the anti-CA125 antibody in murine rat models shows a promising response for ovarian cancer therapy.…”

Section: Ovarian Cancermentioning

confidence: 99%

Microspheres in cancer therapy

Rajput

Agrawal

2010

Indian J Cancer

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Cancer microsphere technology is the latest trend in cancer therapy. It helps the pharmacist to formulate the product with maximum therapeutic value and minimum or negligible range side effects. Cancer is a disease in which the abnormal cells are quite similar to the normal cells, with just minute genetic or functional change. A major disadvantage of anticancer drugs is their lack of selectivity for tumor tissue alone, which causes severe side effects and results in low cure rates. Thus, it is very difficult to target abnormal cells by the conventional method of the drug delivery system. Microsphere technology is probably the only method that can be used for site-specific action, without causing significant side effects on normal cells. This review article describes various microspheres that have been prepared or formulated to exploit microsphere technology for targeted drug therapy in various cancers. We looked at the usefulness of microspheres as a tool for cancer therapy. The current review has been done using PubMed and Medline search with keywords.

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Improvement of Intraperitoneal Chemotherapy for Rat Ovarian Cancer Using Cisplatin‐containing Microspheres

Cited by 12 publications

References 12 publications

Cisplatin‐incorporated Polymeric Micelles Eliminate Nephrotoxicity, While Maintaining Antitumor Activity

Cisplatin‐incorporated Polymeric Micelles Eliminate Nephrotoxicity, While Maintaining Antitumor Activity

trans-[Ru(NO)(NH3)4(py)](BF4)3·H2O encapsulated in PLGA microparticles for delivery of nitric oxide to B16-F10 cells: Cytotoxicity and phototoxicity

Microspheres in cancer therapy

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