cis-Dichlorodiamminoplatinum (II) glyconanoparticles by drug-induced ionic gelation technique targeted to prostate cancer: preparation, optimization and in vitro characterization.

Abstract

BACKGROUND:

Cancer stem cells (CSC) have been proposed as the reason of cancer relapse which are characterized mainly based on CD44+ phenotype with other supplementary markers. The aim of the present study is to fabricate cis-dichlorodiamminoplatinum (II) (CDDP) loaded glyconanoparticles using hyaluronic acid (HA) which is also known as the endogenous substrate for CD44 in vivo.

METHODS:

For this purpose, a drug-induced ionic gelation technique has been used to prepare CDDP-incorporated nanoparticles. To optimize the fabrication technique, stirring rate, stirring time, and HA/CDDP ratio have been selected as the main factors from other factors and subjected to face-centered central composite design for optimization purposes. The optimized nanoparticles were further characterized using different complementary methods including FTIR, SEM, AFM and DSC. To evaluate the biological effectiveness of CDDP nanoparticles release study, MTS assay, tumor cell clonogenicity and sphere formation assay have been performed as well.

RESULTS:

Spherical CDDP nanoparticles with Z-average approx. 150nm with low PdI were prepared by adjusting the selected variables. FTIR results indicated the presence of inclusion complexes between CDDP and HA which lead to preparing nanoparticles with high entrapment efficiency and drug content of 87.4 and 43.74 percentage respectively. In vitro release study showed a sustained release of CDDP up to 4 days, and cellular studies confirmed that nanoparticles formation keeps the anticancer activity of formulated CDDP while moderate increase in cancer stem cell suppression.

CONCLUSION:

It seems hyaluronic acid could be successfully exploited as carrier in cancer-targeted drug delivery with a look at targeting the CSCs.

• Authors: Soheyl Jafari Malek, Reyhaneh Khoshchehreh, Navid Goodarzi, Mohammad Reza Khoshayand, Mohsen Amini, Fatemeh Atyabi, Mehdi Esfandyari-Manesh, Shirin Tehrani, Razieh Mohammad Jafari, Mohammed Shahab Maghazei, Farhad Alvandifar, Marzieh Ebrahimi, Rassoul Dinarvand
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 122 Pg. 350-358 (Oct 01 2014) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 25078298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Gels
• Ions
• Cisplatin

Topics

• Antineoplastic Agents (administration & dosage, pharmacology)
• Calorimetry, Differential Scanning
• Cell Line, Tumor
• Cisplatin (administration & dosage, pharmacology)
• Gels (chemistry)
• Humans
• In Vitro Techniques
• Ions
• Male
• Nanoparticles
• Prostatic Neoplasms (pathology)
• Spectroscopy, Fourier Transform Infrared