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A novel core-shell lipid nanoparticle for improving oral administration of water soluble chemotherapeutic agents: inhibited intestinal hydrolysis and enhanced lymphatic absorption.

The oral administration of water-soluble chemotherapeutical agents is limited by their serious gastrointestinal side effects, instability at intestinal pH, and poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a model drug and developed a novel lipid formulation containing... Full description

Journal Title: Drug delivery November 2017, Vol.24(1), pp.1565-1573
Main Author: Wang, Tao
Other Authors: Shen, Liao , Zhang, Zhen , Li, Haiyan , Huang, Ri , Zhang, Yadan , Quan, Dongqin
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1521-0464 ; DOI: 10.1080/10717544.2017.1386730
Link: http://search.proquest.com/docview/1951415793/?pq-origsite=primo
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recordid: proquest1951415793
title: A novel core-shell lipid nanoparticle for improving oral administration of water soluble chemotherapeutic agents: inhibited intestinal hydrolysis and enhanced lymphatic absorption.
format: Article
creator:
  • Wang, Tao
  • Shen, Liao
  • Zhang, Zhen
  • Li, Haiyan
  • Huang, Ri
  • Zhang, Yadan
  • Quan, Dongqin
subjects:
  • Administration, Oral–Administration & Dosage
  • Animals–Adverse Effects
  • Antineoplastic Agents–Pharmacokinetics
  • Area Under Curve–Chemistry
  • Drug Carriers–Chemistry
  • Drug Stability–Chemistry
  • Hydrogen-Ion Concentration–Administration & Dosage
  • Intestinal Absorption–Adverse Effects
  • Liposomes–Pharmacokinetics
  • Male–Pharmacokinetics
  • Metabolic Clearance Rate–Pharmacokinetics
  • Nanoparticles–Pharmacokinetics
  • Particle Size–Pharmacokinetics
  • Rats–Pharmacokinetics
  • Rats, Wistar–Pharmacokinetics
  • Topotecan–Pharmacokinetics
  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • Topotecan
  • Core-Shell Lipid Nanoparticle
  • Intestinal Lymphatic Transportation
  • Oral Administration
  • Topotecan
  • Water-Soluble Chemotherapeutical Agents
ispartof: Drug delivery, November 2017, Vol.24(1), pp.1565-1573
description: The oral administration of water-soluble chemotherapeutical agents is limited by their serious gastrointestinal side effects, instability at intestinal pH, and poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a model drug and developed a novel lipid formulation containing core-shell lipid nanoparticle (CLN) that makes the water-soluble drug to ‘dissolve’ in oil. TPT molecules can be encapsulated into nanoparticles surrounded by oil barrier while avoiding the direct contact with intestinal environment, thus easing the intestinal hydrolytic degradation and gastrointestinal (GI) irritation. Microstructure and mean particle size of TPT-CLN were characterized by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS), respectively. The average size of nanoparticles was approximately 60 nm with a homogeneous distribution in shapes of spheres or ellipsoid. According to in vitro stability studies, more initial form of TPT was observed in presence of lipid nanoparticle compared with free topotecan solution in artificial intestinal juice (pH 6.5). After oral administration of TPT-CLN in rats, AUC and C max of TPT were all increased compared with free TPT, indicating significant enhancement of oral absorption. Intestinal lymphatic transport was confirmed as the major way for CLN to enhance oral absorption of TPT by the treatment of blocking chylomicron flow. Lower GI irritation of TPT-CLN was observed in the gastrointestinal damage studies. The in vivo antitumor activity of TPT-CLN showed an improved antitumor efficacy by oral treatment of TPT-CLN compared to free TPT. From the obtained data, the systems appear an attractive progress in oral administration of topotecan.
language: eng
source:
identifier: E-ISSN: 1521-0464 ; DOI: 10.1080/10717544.2017.1386730
fulltext: fulltext
issn:
  • 15210464
  • 1521-0464
url: Link


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titleA novel core-shell lipid nanoparticle for improving oral administration of water soluble chemotherapeutic agents: inhibited intestinal hydrolysis and enhanced lymphatic absorption.
creatorWang, Tao ; Shen, Liao ; Zhang, Zhen ; Li, Haiyan ; Huang, Ri ; Zhang, Yadan ; Quan, Dongqin
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ispartofDrug delivery, November 2017, Vol.24(1), pp.1565-1573
identifierE-ISSN: 1521-0464 ; DOI: 10.1080/10717544.2017.1386730
subjectAdministration, Oral–Administration & Dosage ; Animals–Adverse Effects ; Antineoplastic Agents–Pharmacokinetics ; Area Under Curve–Chemistry ; Drug Carriers–Chemistry ; Drug Stability–Chemistry ; Hydrogen-Ion Concentration–Administration & Dosage ; Intestinal Absorption–Adverse Effects ; Liposomes–Pharmacokinetics ; Male–Pharmacokinetics ; Metabolic Clearance Rate–Pharmacokinetics ; Nanoparticles–Pharmacokinetics ; Particle Size–Pharmacokinetics ; Rats–Pharmacokinetics ; Rats, Wistar–Pharmacokinetics ; Topotecan–Pharmacokinetics ; Antineoplastic Agents ; Drug Carriers ; Liposomes ; Topotecan ; Core-Shell Lipid Nanoparticle ; Intestinal Lymphatic Transportation ; Oral Administration ; Topotecan ; Water-Soluble Chemotherapeutical Agents
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descriptionThe oral administration of water-soluble chemotherapeutical agents is limited by their serious gastrointestinal side effects, instability at intestinal pH, and poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a model drug and developed a novel lipid formulation containing core-shell lipid nanoparticle (CLN) that makes the water-soluble drug to ‘dissolve’ in oil. TPT molecules can be encapsulated into nanoparticles surrounded by oil barrier while avoiding the direct contact with intestinal environment, thus easing the intestinal hydrolytic degradation and gastrointestinal (GI) irritation. Microstructure and mean particle size of TPT-CLN were characterized by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS), respectively. The average size of nanoparticles was approximately 60 nm with a homogeneous distribution in shapes of spheres or ellipsoid. According to in vitro stability studies, more initial form of TPT was observed in presence of lipid nanoparticle compared with free topotecan solution in artificial intestinal juice (pH 6.5). After oral administration of TPT-CLN in rats, AUC and C max of TPT were all increased compared with free TPT, indicating significant enhancement of oral absorption. Intestinal lymphatic transport was confirmed as the major way for CLN to enhance oral absorption of TPT by the treatment of blocking chylomicron flow. Lower GI irritation of TPT-CLN was observed in the gastrointestinal damage studies. The in vivo antitumor activity of TPT-CLN showed an improved antitumor efficacy by oral treatment of TPT-CLN compared to free TPT. From the obtained data, the systems appear an attractive progress in oral administration of topotecan.
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titleA novel core-shell lipid nanoparticle for improving oral administration of water soluble chemotherapeutic agents: inhibited intestinal hydrolysis and enhanced lymphatic absorption.
authorWang, Tao ; Shen, Liao ; Zhang, Zhen ; Li, Haiyan ; Huang, Ri ; Zhang, Yadan ; Quan, Dongqin
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