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Poly(Ethylene Oxide)-Modified Poly(β-Amino Ester) Nanoparticles as a pH-Sensitive System for Tumor-Targeted Delivery of Hydrophobic Drugs: Part 2. In Vivo Distribution and Tumor Localization Studies

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Purpose

This study was carried out to determine the biodistribution profiles and tumor localization potential of poly(ethylene oxide) (PEO)-modified poly(β-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(ɛ-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.

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Acknowledgments

This study was supported by the National Cancer Institute grant R01-CA095522 from the National Institutes of Health. The authors thank Professor Robert Campbell for the particle size and zeta potential measurements, Professor Richard Deth for the liquid scintillation counter, and Dr. Ralph Loring for the gamma counter. Dr. Michael Seiden and Dr. Duan Zhenfeng of Massachusetts General Hospital are thanked for providing the SKOV-3 tumor cell lines. Dr. Ananthsrinivas Chakilam is acknowledged for his help in carrying out the noncompartmental pharmacokinetic analysis.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115, USA

    Dinesh Shenoy & Mansoor Amiji

  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Steven Little & Robert Langer

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  1. Dinesh Shenoy
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  4. Mansoor Amiji
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Correspondence to Mansoor Amiji.

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Shenoy, D., Little, S., Langer, R. et al. Poly(Ethylene Oxide)-Modified Poly(β-Amino Ester) Nanoparticles as a pH-Sensitive System for Tumor-Targeted Delivery of Hydrophobic Drugs: Part 2. In Vivo Distribution and Tumor Localization Studies. Pharm Res 22, 2107–2114 (2005). https://doi.org/10.1007/s11095-005-8343-0

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