title: 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.
  
  
  CONCLUSIONS
  It seems hyaluronic acid could be successfully exploited as carrier in cancer-targeted drug delivery with a look at targeting the CSCs.
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Soheyl
authors: S
authors: Jafari Malek
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran.
authors: Reyhaneh
authors: R
authors: Khoshchehreh
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Navid
authors: N
authors: Goodarzi
authors: Department of Drug and Food Control, Faculty of Pharmacy and Pharmaceutical Quality Assurance Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mohammad Reza
authors: MR
authors: Khoshayand
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mohsen
authors: M
authors: Amini
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Fatemeh
authors: F
authors: Atyabi
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Mehdi
authors: M
authors: Esfandyari-Manesh
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Shirin
authors: S
authors: Tehrani
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Razieh
authors: R
authors: Mohammad Jafari
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Mohammed Shahab
authors: MS
authors: Maghazei
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Farhad
authors: F
authors: Alvandifar
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 19395-4644, Iran. Electronic address: mebrahimi@royaninstitute.org.
authors: Marzieh
authors: M
authors: Ebrahimi
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran. Electronic address: dinarvand@tums.ac.ir.
authors: Rassoul
authors: R
authors: Dinarvand
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D005782:Gels / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D007477:Ions; D008297:Male; D053758:Nanoparticles; D011471:Prostatic Neoplasms / Q000473:pathology*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D005782:Gels; D007477:Ions; D002945:Cisplatin
keywords: Cancer stem cell; Hyaluronic acid; Nanomedicine; Polysaccharide; Prostate cancer