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In vivo study of doxorubicin-loaded cell-penetrating peptide-modified pH-sensitive liposomes: biocompatibility, bio-distribution, and pharmacodynamics in BALB/c nude mice bearing human breast tumors.(ORIGINAL RESEARCH)

In vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensiti... Full description

Journal Title: Drug Design Development and Therapy, Annual, 2017, Vol.11, p.3105(13)
Main Author: Ding, Yuan
Other Authors: Cui, Wei , Sun, Dan , Wang, Gui - Ling , Hei, Yu , Meng, Shuai , Chen, Jian - Hua , Xie, Ying , Wang, Zhi - Qiang
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1177-8881 ; DOI: 10.2147/DDDT.S149814
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recordid: gale_hrca531884818
title: In vivo study of doxorubicin-loaded cell-penetrating peptide-modified pH-sensitive liposomes: biocompatibility, bio-distribution, and pharmacodynamics in BALB/c nude mice bearing human breast tumors.(ORIGINAL RESEARCH)
format: Article
creator:
  • Ding, Yuan
  • Cui, Wei
  • Sun, Dan
  • Wang, Gui - Ling
  • Hei, Yu
  • Meng, Shuai
  • Chen, Jian - Hua
  • Xie, Ying
  • Wang, Zhi - Qiang
subjects:
  • Peptides -- Health Aspects
  • Breast Cancer -- Research
  • Breast Cancer -- Health Aspects
  • Ph -- Health Aspects
  • Anthracyclines -- Research
  • Anthracyclines -- Health Aspects
  • Drug Delivery Systems -- Health Aspects
  • Polyethylene Glycol -- Health Aspects
  • Polyols -- Health Aspects
ispartof: Drug Design, Development and Therapy, Annual, 2017, Vol.11, p.3105(13)
description: In vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p
language: English
source:
identifier: ISSN: 1177-8881 ; DOI: 10.2147/DDDT.S149814
fulltext: fulltext
issn:
  • 1177-8881
  • 11778881
url: Link


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titleIn vivo study of doxorubicin-loaded cell-penetrating peptide-modified pH-sensitive liposomes: biocompatibility, bio-distribution, and pharmacodynamics in BALB/c nude mice bearing human breast tumors.(ORIGINAL RESEARCH)
creatorDing, Yuan ; Cui, Wei ; Sun, Dan ; Wang, Gui - Ling ; Hei, Yu ; Meng, Shuai ; Chen, Jian - Hua ; Xie, Ying ; Wang, Zhi - Qiang
ispartofDrug Design, Development and Therapy, Annual, 2017, Vol.11, p.3105(13)
identifierISSN: 1177-8881 ; DOI: 10.2147/DDDT.S149814
subjectPeptides -- Health Aspects ; Breast Cancer -- Research ; Breast Cancer -- Health Aspects ; Ph -- Health Aspects ; Anthracyclines -- Research ; Anthracyclines -- Health Aspects ; Drug Delivery Systems -- Health Aspects ; Polyethylene Glycol -- Health Aspects ; Polyols -- Health Aspects
descriptionIn vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p<0.01) and resulted in more cell apoptosis as a result of DNA disruption as well as a relatively lower tumor growth ratio (T/C%). Histological examination did not show any signs of necrosis or inflammation in normal tissues, but large cell dissolving areas were found in tumors following the treatment of animals with CPPL(DOX). Our findings provide important and detailed information regarding the distribution of CPPL(DOX) in vivo and reveal their abilities of tumor penetration and potential for the treatment of breast cancer. Keywords: tumor targeting, TUNEL stain, hemolysis, therapy for breast cancer, pharmacokinetics
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titleIn vivo study of doxorubicin-loaded cell-penetrating peptide-modified pH-sensitive liposomes: biocompatibility, bio-distribution, and pharmacodynamics in BALB/c nude mice bearing human breast tumors.(ORIGINAL RESEARCH)
descriptionIn vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p<0.01) and resulted in more cell apoptosis as a result of DNA disruption as well as a relatively lower tumor growth ratio (T/C%). Histological examination did not show any signs of necrosis or inflammation in normal tissues, but large cell dissolving areas were found in tumors following the treatment of animals with CPPL(DOX). Our findings provide important and detailed information regarding the distribution of CPPL(DOX) in vivo and reveal their abilities of tumor penetration and potential for the treatment of breast cancer. Keywords: tumor targeting, TUNEL stain, hemolysis, therapy for breast cancer, pharmacokinetics
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titleIn vivo study of doxorubicin-loaded cell-penetrating peptide-modified pH-sensitive liposomes: biocompatibility, bio-distribution, and pharmacodynamics in BALB/c nude mice bearing human breast tumors.(ORIGINAL RESEARCH)
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abstractIn vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p<0.01) and resulted in more cell apoptosis as a result of DNA disruption as well as a relatively lower tumor growth ratio (T/C%). Histological examination did not show any signs of necrosis or inflammation in normal tissues, but large cell dissolving areas were found in tumors following the treatment of animals with CPPL(DOX). Our findings provide important and detailed information regarding the distribution of CPPL(DOX) in vivo and reveal their abilities of tumor penetration and potential for the treatment of breast cancer. Keywords: tumor targeting, TUNEL stain, hemolysis, therapy for breast cancer, pharmacokinetics
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