Pharmaceutical Research

, Volume 32, Issue 6, pp 1947–1956 | Cite as

Polypeptide-based Micelles for Delivery of Irinotecan: Physicochemical and In vivo Characterization

  • Thiruganesh Ramasamy
  • Ju Yeon Choi
  • Hyuk Jun Cho
  • Subbaih Kandasamy Umadevi
  • Beom Soo Shin
  • Han-Gon Choi
  • Chul Soon Yong
  • Jong Oh Kim
Research Paper



Irinotecan (IRI) is a broad spectrum chemotherapeutic agent used individually or in combination to treat multiple malignancies. Present study aimed at developing polypeptide-based block ionomer complex (BIC) micelles to improve the pharmacokinetic and antitumor response of IRI.


Irinotecan-loaded BIC micelles (IRI-BIC) was prepared and evaluated in terms of various physicochemical and biological parameters including size, shape, release, cytotoxicity, and pharmacokinetic analysis. In vivo antitumor efficacy was investigated in SCC-7 bearing xenograft tumor model.


IRI was successfully incorporated into the ionic cores of poly(ethylene glycol)-b-poly(aspartic acid) (PEG-b-PAA) with a high drug loading capacity (~80%). The electrostatically assembled BIC micelles were nanosized (~50 nm) with uniform size distribution pattern (PDI~0.1). The BIC micelles exhibited pH-sensitiveness with limited release of IRI at physiological conditions and significantly enhanced the release rate at acidic conditions, making it an ideal delivery system for tumor targeting. The IRI-BIC showed a dose-dependent cytotoxicity in SCC-7 and A-549 cancer cell lines. Pharmacokinetic studies clearly showed that BIC micelles improved the IRI blood circulation time and decreased its elimination rate constant, while that of free IRI, rapidly eliminated from the central compartment. Moreover, IRI-BIC showed superior therapeutic performance with no toxicity in BALB/c nude xenograft mice. The micelle treated group showed an inhibition rate of ~66% compared to free IRI treated group.


Taken together, BIC micelles could be a potentially useful nanovehicle with promising applicability in systemic tumor treatment.


anticancer block ionomer complex irinotecan polypeptide self-assembly 



Acetate buffered saline


The area under the drug concentration–time curve from 0 to 24 h


Block ionomer complex




The peak concentration of drug


Dynamic light scattering


Enhanced permeation and retention effect


Fourier transform infrared spectroscopy




Irinotecan-loaded BIC


Elimination rate constant


Mean retention time


Phosphate buffered saline


Polydispersity index


Poly(ethylene glycol)-b-poly(aspartic acid)




Transmission electron microscope


The time to reach the peak concentration


Volume of distribution


X-ray diffractometer


Acknowledgments and Disclosures

This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (No. 2012R1A2A2A02044997 and No.2012R1A1A1039059).

Supplementary material

11095_2014_1588_MOESM1_ESM.docx (57 kb)
ESM 1 (DOCX 56 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Thiruganesh Ramasamy
    • 1
  • Ju Yeon Choi
    • 1
  • Hyuk Jun Cho
    • 1
  • Subbaih Kandasamy Umadevi
    • 2
  • Beom Soo Shin
    • 3
  • Han-Gon Choi
    • 4
  • Chul Soon Yong
    • 1
  • Jong Oh Kim
    • 1
  1. 1.College of PharmacyYeungnam UniversityGyeongsanSouth Korea
  2. 2.St. Paul’s College of PharmacyOsmania UniversityHyderabadIndia
  3. 3.College of PharmacyCatholic University of DaeguGyeongsanSouth Korea
  4. 4.College of Pharmacy, Institute of Pharmaceutical Science and TechnologyHanyang UniversitySangnok-guSouth Korea

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