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Pharmaceutical Research

, Volume 33, Issue 8, pp 2010–2024 | Cite as

Nanoparticles Based on Linear and Star-Shaped Poly(Ethylene Glycol)-Poly(ε-Caprolactone) Copolymers for the Delivery of Antitubulin Drug

  • Karim S. Shalaby
  • Mahmoud E. Soliman
  • Giulia Bonacucina
  • Marco Cespi
  • Giovanni F. Palmieri
  • Omaima A. Sammour
  • Abdelhameed A. El Shamy
  • Lisbeth Illum
  • Luca Casettari
Research Paper

ABSTRACT

Purpose

Biodegradable polymeric nanoparticles of different architectures based on polyethylene glycol-co-poly(ε-caprolactone) block copolymers have been loaded with noscapine (NOS) to study their effect on its anticancer activity. It was intended to use solubility of NOS in an acidic environment and ability of the nanoparticles to passively target drugs into cancer tissue to modify the NOS pharmacokinetic properties and reduce the requirement for frequent injections.

Methods

Linear and star-shaped copolymers were synthetized and used to formulate NOS loaded nanoparticles. Cytotoxicity was performed using a sulforhodamine B method on MCF-7 cells, while biocompatibility was determined on rats followed by hematological and histopathological investigations.

Results

Formulae with the smallest particle sizes and adequate entrapment efficiency revealed that NOS loaded nanoparticles showed higher extent of release at pH 4.5. Colloidal stability suggested that nanoparticles would be stable in blood when injected into the systemic circulation. Loaded nanoparticles had IC50 values lower than free drug. Hematological and histopathological studies showed no difference between treated and control groups. Pharmacokinetic analysis revealed that formulation P1 had a prolonged half-life and better bioavailability compared to drug solution.

Conclusions

Formulation of NOS into biodegradable polymeric nanoparticles has increased its efficacy and residence on cancer cells while passively avoiding normal body tissues.

Graphical Abstract

KEY WORDS

noscapine passive targeting pH dependent release polyethylene glycol-co-poly(ε-caprolactone) (PEG-co-PCL) polymeric nanoparticles 

ABBREVIATIONS

AFM

Atomic force microscopy

CMC

Critical micelle concentration

DLS

Dynamic light scattering

HPLC

High performance liquid chromatography

NOS

Noscapine

NPs

Nanoparticles

PEG-co-PCL

Polyethylene glycol-co-poly(ε-caprolactone) block copolymers

PLA

Poly(lactic acid)

PLGA

Poly(lactide-co-glycolide)

RES

Reticuloendothelial system

SRB

Sulphorhodamine-B

Supplementary material

11095_2016_1939_MOESM1_ESM.docx (526 kb)
ESM 1 (DOCX 526 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Karim S. Shalaby
    • 1
  • Mahmoud E. Soliman
    • 1
  • Giulia Bonacucina
    • 2
  • Marco Cespi
    • 2
  • Giovanni F. Palmieri
    • 2
  • Omaima A. Sammour
    • 1
  • Abdelhameed A. El Shamy
    • 1
  • Lisbeth Illum
    • 3
  • Luca Casettari
    • 4
  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyAin Shams UniversityCairoEgypt
  2. 2.School of PharmacyUniversity of CamerinoCamerinoItaly
  3. 3.IDentityNottinghamUK
  4. 4.Department of Biomolecular Sciences, School of PharmacyUniversity of UrbinoUrbinoItaly

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