PMID- 25208603
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20141230
IS  - 2042-7158 (Electronic)
IS  - 0022-3573 (Linking)
VI  - 67
IP  - 1
DP  - 2015 Jan
TI  - Nucleotropic doxorubicin nanoparticles decrease cancer cell viability, destroy 
      mitochondria, induce autophagy and enhance tumour necrosis.
PG  - 68-77
LID - 10.1111/jphp.12322 [doi]
AB  - OBJECTIVE: Doxorubicin (Dox) is used clinically against various neoplasias, but 
      suffers from serious side effects, and for the past three decades, this 
      shortcoming has spurred research towards finding better drug delivery systems 
      (DDSs) for this frontline drug. METHODS: A non-targeted nucleotropic Dox-loaded 
      nanoparticle (DNP) DDS is described, which has a simple chemical design, is easy 
      to formulate and administer, is inexpensive, non-biohazardous and may prove to be 
      useful clinically. KEY FINDINGS: The DNP formulated via vortex-assisted complex 
      coarcevation enhanced (300-fold) cell-inhibitory activity of the drug in a panel 
      of human cancer cells (osteosarcoma, breast, prostate and colorectal cancer) and 
      enhanced (10-fold) efficacy against osteosarcoma (OS) in vivo. The slow-release 
      DNPs localised to the endoplasmic reticulum disrupted the mitochondria and 
      entered the nucleus. Prominent cytosolic vacuolisation, budding off of portions 
      of the cytoplasm, both suggestive of autophagy, were observed. Mice that were 
      administered with DNPs intratumorally had the smallest tumours at the end of the 
      study, with more necrotic hotspots. CONCLUSION: This promising nucleotropic DDS 
      enhances the cell delivery and activity of Dox against a variety of human cancer 
      cell lines and in OS tumours in mice.
CI  - (c) 2014 Royal Pharmaceutical Society.
FAU - Friedhuber, Anna M
AU  - Friedhuber AM
AD  - Department of Pathology, University of Melbourne, Melbourne, Australia.
FAU - Chandolu, Vijay
AU  - Chandolu V
FAU - Manchun, Somkamon
AU  - Manchun S
FAU - Donkor, Osaana
AU  - Donkor O
FAU - Sriamornsak, Pornsak
AU  - Sriamornsak P
FAU - Dass, Crispin R
AU  - Dass CR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140911
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Delayed-Action Preparations)
RN  - 80168379AG (Doxorubicin)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Chemistry, Pharmaceutical
MH  - Chitosan/chemistry
MH  - Delayed-Action Preparations
MH  - Doxorubicin/*administration & dosage/*pharmacology
MH  - Drug Delivery Systems
MH  - Drug Liberation
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mitochondria/drug effects
MH  - Nanoparticles/*chemistry
OTO - NOTNLM
OT  - cancer
OT  - doxorubicin
OT  - efficacy
OT  - nanoparticle
OT  - nucleus
EDAT- 2014/09/12 06:00
MHDA- 2016/02/18 06:00
CRDT- 2014/09/12 06:00
PHST- 2014/04/23 00:00 [received]
PHST- 2014/08/10 00:00 [accepted]
PHST- 2014/09/12 06:00 [entrez]
PHST- 2014/09/12 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - 10.1111/jphp.12322 [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 2015 Jan;67(1):68-77. doi: 10.1111/jphp.12322. Epub 2014 Sep 
      11.