PMID- 27667706
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20181202
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 96
DP  - 2017 Jan 1
TI  - Enhanced in vitro cytotoxicity and anti-tumor activity of vorinostat-loaded 
      pluronic micelles with prolonged release and reduced hepatic and renal 
      toxicities.
PG  - 232-242
LID - S0928-0987(16)30394-3 [pii]
LID - 10.1016/j.ejps.2016.09.029 [doi]
AB  - Vorinostat is the first histone deacetylase inhibitor approved by US FDA for use 
      in cancer therapy. However, its limited aqueous solubility, low permeability, and 
      suboptimal pharmacokinetics hinder its delivery. Thus, in this study, micelles of 
      vorinostat with each of pluronic F68 (PF68) and pluronic F127 (PF127) were 
      developed and optimized based on drug loading and entrapment. The optimized 
      micelles were characterized using Fourier transform infrared spectroscopy 
      (FT-IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), 
      zeta analyzer, and electron transmission microscopy. Their in vitro release, 
      stability, in vitro cytotoxicity against HepG2, Caco-2, and MCF-7 cell lines, and 
      finally, in vivo antitumor activity in mice bearing Ehrlich Ascites Carcinoma 
      (EAC) were assessed. The highest entrapment efficiency was 99.09+/-2.16% and 
      94.19+/-2.37% for micelles of 1:50 drug to polymer ratio with each of PF127 and 
      PF68, respectively. These micelles were nearly spherical with nanoscopic mean 
      diameters of 72.61+/-10.66nm for PF68 and 91.88+/-10.70nm for PF127 with narrow size 
      distribution. The micelles provided prolonged release at phosphate buffer saline 
      pH7.4 up to 24h for PF68 and 72h for PF127. Potentiation of in vitro cytotoxicity 
      of vorinostat was more pronounced with PF127 micelles particularly against MCF-7 
      cells. Compared with free vorinostat, the micelles with PF127 were more effective 
      in inhibiting tumor growth as well as exhibiting significantly (p<0.05) 
      diminished hepatic and renal toxicities. In conclusion, 1:50 vorinostat-PF127 
      micelles may facilitate i.v. formulations and can be suggested as a promising 
      stable and safe nanoparticulate delivery system with prolonged release and 
      potentiated cytotoxicity.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Mohamed, Elham Abdelmonem
AU  - Mohamed EA
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt. Electronic address: elhamelsaid@yahoo.com.
FAU - Abu Hashim, Irhan Ibrahim
AU  - Abu Hashim II
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt.
FAU - Yusif, Rehab Mohammad
AU  - Yusif RM
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt; Department of Pharmaceutics and Pharmaceutical Technology, College 
      of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41411, Saudi Arabia.
FAU - Suddek, Ghada Mohamed
AU  - Suddek GM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura 35516, Egypt.
FAU - Shaaban, Ahmed Abdel Aziz
AU  - Shaaban AAA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura 35516, Egypt.
FAU - Badria, Farid Abd Elreheem
AU  - Badria FAE
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20160922
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cytotoxins)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Carriers)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Micelles)
RN  - 106392-12-5 (Poloxamer)
RN  - 58IFB293JI (Vorinostat)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage/toxicity
MH  - Caco-2 Cells
MH  - Carcinoma, Ehrlich Tumor/drug therapy/pathology
MH  - Cytotoxins/*administration & dosage/toxicity
MH  - Delayed-Action Preparations/administration & dosage/toxicity
MH  - Drug Carriers/*administration & dosage/toxicity
MH  - Female
MH  - Hep G2 Cells
MH  - Humans
MH  - Hydroxamic Acids/*administration & dosage/toxicity
MH  - Kidney/drug effects/pathology
MH  - Liver/drug effects/pathology
MH  - MCF-7 Cells
MH  - Mice
MH  - *Micelles
MH  - Poloxamer/*administration & dosage/toxicity
MH  - Vorinostat
OTO - NOTNLM
OT  - Antitumor activity
OT  - In vitro cytotoxicity
OT  - Pluronic
OT  - Polymeric micelles
OT  - Vorinostat
EDAT- 2016/10/28 06:00
MHDA- 2017/04/07 06:00
CRDT- 2016/09/27 06:00
PHST- 2016/04/27 00:00 [received]
PHST- 2016/08/16 00:00 [revised]
PHST- 2016/09/21 00:00 [accepted]
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
PHST- 2016/09/27 06:00 [entrez]
AID - S0928-0987(16)30394-3 [pii]
AID - 10.1016/j.ejps.2016.09.029 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2017 Jan 1;96:232-242. doi: 10.1016/j.ejps.2016.09.029. Epub 
      2016 Sep 22.