Drug Delivery Systems: The Industrial View

Yokoyama, Kazumasa; Ueda, Yoshinori; Kikukawa, A.; Yamanouchi, Kouichi

doi:10.1007/978-1-4684-9001-5_13

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…46 Acidic conditions, often found in tumor tissues might play an important role for tumor selectivity of the conjugate because the release of doxorubicin from the conjugate increases with decreasing pH. 47 Fluorescence studies showed intracellular distribution of the conjugate in cytosol within 30 min of administration and in nuclei after 6 h. 48 These characteristics and the lower toxicity of the conjugate in animal studies compared with doxorubicin alone encouraged the study of this drug in a phase I clinical trial. Based on the information generated by preclinical studies, dextran-doxorubicin conjugate was tested in a phase I clinical trial where an i.v.…”

Section: Protection Of Conjugated Drugs From Biodegradationmentioning

confidence: 99%

“…However, the current knowledge for the mechanism of action of conjugate is still not completely known despite of having proved preclinical studies suggesting its antitumor activity and its accumulation in tumor tissues 46. Acidic conditions, often found in tumor tissues might play an important role for tumor selectivity of the conjugate because the release of doxorubicin from the conjugate increases with decreasing pH 47. Fluorescence studies showed intracellular distribution of the conjugate in cytosol within 30 min of administration and in nuclei after 6 h 48.…”

Section: Dextran–doxorubicin Conjugatementioning

confidence: 99%

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Dextran–doxorubicin/chitosan nanoparticles for solid tumor therapy

Bisht

Maitra

2009

WIREs Nanomed Nanobiotechnol

104

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Chemotherapy is a major therapeutic approach for the treatment of localized and metastasized cancers. Whereas potent chemotherapeutic agents seem promising in the test tube, clinical trials often fail due to unfavorable pharmacokinetics, poor delivery, low local concentrations, and limited accumulation in the target cell. The pathophysiology of the tumor vasculature and stromal compartment presents a major obstacle to effective delivery of agents to solid tumors. Poor perfusion of the tumor, arterio-venous shunting, necrotic and hypoxic areas, as well as a high interstitial fluid pressure work against favorable drug uptake. Thus, targeted drug delivery using long-circulating particulate drug carriers such as hydrogels of controlled size (<100 nm diameter) holds immense potential to improve the treatment of cancer by selectively providing therapeutically effective drug concentrations at the tumor site [through enhanced permeability and retention (EPR) effect] while reducing undesirable side effects. This review focuses on the progress of targeted delivery of nanoparticulated anticancer drug such as doxorubicin chemically conjugated with dextran and encapsulated in chitosan nanoparticles to solid tumor with reduced side effect of drug. Regulated particle size and long circulation of these hydrogel nanoparticles in blood help them accumulate in tumor tissue through EPR effect as evident from the significant regression of the tumor volume. The cardiotoxicity of doxorubicin can be minimized by coupling the drug with dextran and encapsulating it in chitosan nanoparticles.

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Section: Protection Of Conjugated Drugs From Biodegradationmentioning

confidence: 99%

Section: Dextran–doxorubicin Conjugatementioning

confidence: 99%

Dextran–doxorubicin/chitosan nanoparticles for solid tumor therapy

Bisht

Maitra

2009

WIREs Nanomed Nanobiotechnol

104

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Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD)

et al. 1993

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Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21-28 days. Thirteen patients have received a total of 24 courses (median 2; range 1-3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 x WHO grade IV, 1 x WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 x WHO grade IV, 2 x WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 micrograms/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83-80.21 micrograms/ml*h with dose-dependent elimination half lives (t1/2 alpha: 0.02-0.87 h; t1/2 beta: 2.69-11.58 h; t1/2 gamma: 41.44-136.58 h).(ABSTRACT TRUNCATED AT 250 WORDS)

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Lipo-prostaglandin preparations

Mizushima

1991

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Drug Delivery Systems: The Industrial View

Cited by 3 publications

References 9 publications

Dextran–doxorubicin/chitosan nanoparticles for solid tumor therapy

Dextran–doxorubicin/chitosan nanoparticles for solid tumor therapy

Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD)

Lipo-prostaglandin preparations

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