Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 2. In vivo distribution and tumor localization studies.

Abstract

PURPOSE:

This study was carried out to determine the biodistribution profiles and tumor localization potential of poly(ethylene oxide) (PEO)-modified poly(beta-amino ester) (PbAE) as a novel, pH-sensitive biodegradable polymeric nanoparticulate system for tumor-targeted drug delivery.

METHODS:

The biodistribution studies of PEO-modified PbAE and PEO-modified poly(epsilon-caprolactone) (PCL), a non-pH-sensitive polymer, nanoparticle systems were carried out in normal mice using 111indium-oxine [111In] as a lipophilic radiolabel encapsulated within the polymeric matrix, and the distribution of the nanoparticles was studied in plasma and all the vital organs following intravenous administration. Solid tumors were developed on nude mice using human ovarian carcinoma xenograft (SKOV-3) and the change in concentrations of tritium [3H]-labeled paclitaxel encapsulated in polymeric nanoparticles was examined in blood, tumor mass, and liver.

RESULTS:

Study in normal mice with a gamma-emitting isotope [111In] provided a thorough biodistribution analysis of the PEO-modified nanoparticulate carrier systems, whereas 3H-paclitaxel was useful to understand the change in concentration and tumor localization of anticancer compound directly in major sites of distribution. Both PEO-PbAE and PEO-PCL nanoparticles showed long systemic circulating properties by virtue of surface modification with PEO-containing triblock block copolymer (Pluronic stabilizer. Although the PCL nanoparticles showed higher uptake by the reticuloendothelial system, the PbAE nanoparticles effectively delivered the encapsulated payload into the tumor mass.

CONCLUSIONS:

PEO-modified PbAE nanoparticles showed considerable passive tumor targeting potential in early stages of biodistribution via the enhanced permeation and retention (EPR) mechanism. This prompts a detailed biodistribution profiling of the nanocarrier for prolonged periods to provide conclusive evidence for superiority of the delivery system.

• Authors: Dinesh Shenoy, Steven Little, Robert Langer, Mansoor Amiji
• Journal: Pharmaceutical research (Pharm Res) Vol. 22 Issue 12 Pg. 2107-14 (Dec 2005) ISSN: 0724-8741 [Print] United States
• PMID: 16254763 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amino Acids
• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Indium Radioisotopes
• Surface-Active Agents
• Polyethylene Glycols
• Paclitaxel

Topics

• Amino Acids (chemistry)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology)
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics, pharmacology)
• Cell Line, Tumor
• Drug Delivery Systems
• Female
• Half-Life
• Humans
• Hydrogen-Ion Concentration
• Indium Radioisotopes
• Mice
• Mice, Nude
• Nanostructures
• Neoplasm Transplantation
• Paclitaxel (administration & dosage, pharmacokinetics, pharmacology)
• Polyethylene Glycols (chemistry)
• Surface-Active Agents
• Tissue Distribution