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Peptide-Mediated Liposomal Doxorubicin Enhances Drug Delivery Efficiency and Therapeutic Efficacy in Animal Models

Lung cancer ranks among the most common malignancies, and is the leading cause of cancer-related mortality worldwide. Chemotherapy for lung cancer can be made more specific to tumor cells, and less toxic to normal tissues, through the use of ligand-mediated drug delivery systems. In this study, we i... Full description

Journal Title: PLoS One Dec 2013, Vol.8(12), p.e83239
Main Author: De-Kuan, Chang
Other Authors: Pi-Chun, Li , Han-Chung, Wu
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0083239
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title: Peptide-Mediated Liposomal Doxorubicin Enhances Drug Delivery Efficiency and Therapeutic Efficacy in Animal Models
format: Article
creator:
  • De-Kuan, Chang
  • Pi-Chun, Li
  • Han-Chung, Wu
subjects:
  • Taiwan
  • Liposomes
  • Side Effects
  • Cancer
  • Nanoparticles
  • Cancer Therapies
  • Non-Small Cell Lung Carcinoma
  • Pharmacology
  • Doxorubicin
  • Biology
  • Endocytosis
  • Peptides
  • Metastases
  • Animal Models
  • Drug Dosages
  • Drug Therapy
  • Lung
  • Chemotherapy
  • Bioavailability
  • Tumor Cells
  • Conjugation
  • Lung Cancer
  • Drug Delivery Systems
  • Chemotherapy
  • Cancer
  • Ligands
  • Effectiveness
  • Drug Delivery Systems
  • Animal Models
  • Bioavailability
  • Ligands
  • Biocompatibility
  • Animal Tissues
  • Drug Delivery
  • Antigens
  • Chemotherapy
  • Doxorubicin
  • Tumors
  • Polyethylene Glycol
  • Liposomes
  • Drugs
  • Lung Cancer
  • Chemotherapy
  • Bioavailability
  • Liposomes
  • Mouse Models
  • Cancer Treatment
  • Drug Delivery
  • Lung and Intrathoracic Tumors
  • Animal Models
  • Endocytosis
  • Body Weight
ispartof: PLoS One, Dec 2013, Vol.8(12), p.e83239
description: Lung cancer ranks among the most common malignancies, and is the leading cause of cancer-related mortality worldwide. Chemotherapy for lung cancer can be made more specific to tumor cells, and less toxic to normal tissues, through the use of ligand-mediated drug delivery systems. In this study, we investigated the targeting mechanism of the ligand-mediated drug delivery system using a peptide, SP5-2, which specifically binds to non-small cell lung cancer (NSCLC) cells. Conjugation of SP5-2 to liposomes enhanced the amount of drug delivered directly into NSCLC cells, through receptor-mediated endocytosis. Functional SP5-2 improved the therapeutic index of Lipo-Dox by enhancing therapeutic efficacy, reducing side effects, and increasing the survival rate of tumor-bearing mice in syngenic, metastatic and orthotopic animal models. Accumulation of SP5-2-conjugated liposomal doxorubicin (SP5-2-LD) in tumor tissues was 11.2-fold higher than that of free doxorubicin, and the area under the concentration-time curve (AUC0–72 hours) was increased 159.2-fold. Furthermore, the experiment of bioavailability was assessed to confirm that SP5-2 elevates the uptake of the liposomal drugs by the tumor cells in vivo. In conclusion, the use of SP5-2-conjugated liposomes enhances pharmacokinetic properties, improves efficacy and safety profiles, and allows for controlled biodistribution and drug release.
language: eng
source:
identifier: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0083239
fulltext: fulltext_linktorsrc
issn:
  • 19326203
  • 1932-6203
url: Link


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titlePeptide-Mediated Liposomal Doxorubicin Enhances Drug Delivery Efficiency and Therapeutic Efficacy in Animal Models
creatorDe-Kuan, Chang ; Pi-Chun, Li ; Han-Chung, Wu
ispartofPLoS One, Dec 2013, Vol.8(12), p.e83239
identifierE-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0083239
subjectTaiwan ; Liposomes ; Side Effects ; Cancer ; Nanoparticles ; Cancer Therapies ; Non-Small Cell Lung Carcinoma ; Pharmacology ; Doxorubicin ; Biology ; Endocytosis ; Peptides ; Metastases ; Animal Models ; Drug Dosages ; Drug Therapy ; Lung ; Chemotherapy ; Bioavailability ; Tumor Cells ; Conjugation ; Lung Cancer ; Drug Delivery Systems ; Chemotherapy ; Cancer ; Ligands ; Effectiveness ; Drug Delivery Systems ; Animal Models ; Bioavailability ; Ligands ; Biocompatibility ; Animal Tissues ; Drug Delivery ; Antigens ; Chemotherapy ; Doxorubicin ; Tumors ; Polyethylene Glycol ; Liposomes ; Drugs ; Lung Cancer ; Chemotherapy ; Bioavailability ; Liposomes ; Mouse Models ; Cancer Treatment ; Drug Delivery ; Lung and Intrathoracic Tumors ; Animal Models ; Endocytosis ; Body Weight
descriptionLung cancer ranks among the most common malignancies, and is the leading cause of cancer-related mortality worldwide. Chemotherapy for lung cancer can be made more specific to tumor cells, and less toxic to normal tissues, through the use of ligand-mediated drug delivery systems. In this study, we investigated the targeting mechanism of the ligand-mediated drug delivery system using a peptide, SP5-2, which specifically binds to non-small cell lung cancer (NSCLC) cells. Conjugation of SP5-2 to liposomes enhanced the amount of drug delivered directly into NSCLC cells, through receptor-mediated endocytosis. Functional SP5-2 improved the therapeutic index of Lipo-Dox by enhancing therapeutic efficacy, reducing side effects, and increasing the survival rate of tumor-bearing mice in syngenic, metastatic and orthotopic animal models. Accumulation of SP5-2-conjugated liposomal doxorubicin (SP5-2-LD) in tumor tissues was 11.2-fold higher than that of free doxorubicin, and the area under the concentration-time curve (AUC0–72 hours) was increased 159.2-fold. Furthermore, the experiment of bioavailability was assessed to confirm that SP5-2 elevates the uptake of the liposomal drugs by the tumor cells in vivo. In conclusion, the use of SP5-2-conjugated liposomes enhances pharmacokinetic properties, improves efficacy and safety profiles, and allows for controlled biodistribution and drug release.
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citationpf e83239 vol 8 issue 12
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titlePeptide-Mediated Liposomal Doxorubicin Enhances Drug Delivery Efficiency and Therapeutic Efficacy in Animal Models
authorDe-Kuan, Chang ; Pi-Chun, Li ; Han-Chung, Wu
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9Biology
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abstractLung cancer ranks among the most common malignancies, and is the leading cause of cancer-related mortality worldwide. Chemotherapy for lung cancer can be made more specific to tumor cells, and less toxic to normal tissues, through the use of ligand-mediated drug delivery systems. In this study, we investigated the targeting mechanism of the ligand-mediated drug delivery system using a peptide, SP5-2, which specifically binds to non-small cell lung cancer (NSCLC) cells. Conjugation of SP5-2 to liposomes enhanced the amount of drug delivered directly into NSCLC cells, through receptor-mediated endocytosis. Functional SP5-2 improved the therapeutic index of Lipo-Dox by enhancing therapeutic efficacy, reducing side effects, and increasing the survival rate of tumor-bearing mice in syngenic, metastatic and orthotopic animal models. Accumulation of SP5-2-conjugated liposomal doxorubicin (SP5-2-LD) in tumor tissues was 11.2-fold higher than that of free doxorubicin, and the area under the concentration-time curve (AUC0–72 hours) was increased 159.2-fold. Furthermore, the experiment of bioavailability was assessed to confirm that SP5-2 elevates the uptake of the liposomal drugs by the tumor cells in vivo. In conclusion, the use of SP5-2-conjugated liposomes enhances pharmacokinetic properties, improves efficacy and safety profiles, and allows for controlled biodistribution and drug release.
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