PMID- 26587994
OWN - NLM
STAT- MEDLINE
DCOM- 20160930
LR  - 20160104
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 13
IP  - 1
DP  - 2016 Jan 4
TI  - Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using 
      Subcellularly "Targeted" Drug Delivery Systems.
PG  - 1-7
LID - 10.1021/acs.molpharmaceut.5b00697 [doi]
AB  - Many drugs have been designed to act on intracellular targets and to affect 
      intracellular processes inside target cells. For the desired effects to be 
      exerted, these drugs should permeate target cells and reach specific 
      intracellular organelles. This subcellular drug targeting approach has been 
      proposed for enhancement of accumulation of these drugs in target organelles and 
      improved efficiency. This approach is based on drug encapsulation in drug 
      delivery systems (DDSs) and/or their decoration with specific targeting moieties 
      that are intended to enhance the drug/DDS accumulation in the intracellular 
      organelle of interest. During recent years, there has been a constant increase in 
      interest in DDSs targeted to specific intracellular organelles, and many 
      different approaches have been proposed for attaining efficient drug delivery to 
      specific organelles of interest. However, it appears that in many studies 
      insufficient efforts have been devoted to quantitative analysis of the major 
      formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and 
      endosomal escape, intracellular trafficking, and efficiency of DDS delivery to 
      the target organelle) and of the resulting pharmacological effects. Thus, in many 
      cases, claims regarding efficient delivery of drug/DDS to a specific organelle 
      and efficient subcellular targeting appear to be exaggerated. On the basis of the 
      available experimental data, it appears that drugs/DDS decoration with specific 
      targeting residues can affect their intracellular fate and result in preferential 
      drug accumulation within an organelle of interest. However, it is not clear 
      whether these approaches will be efficient in in vivo settings and be translated 
      into preclinical and clinical applications. Studies that quantitatively assess 
      the mechanisms, barriers, and efficiencies of subcellular drug delivery and of 
      the associated toxic effects are required to determine the therapeutic potential 
      of subcellular DDS targeting.
FAU - Maity, Amit Ranjan
AU  - Maity AR
AD  - Department of Clinical Biochemistry and Pharmacology, The Faculty of Health 
      Sciences, Ben-Gurion University of the Negev , P.O. Box 653, Beer Sheva 84105, 
      Israel.
FAU - Stepensky, David
AU  - Stepensky D
AD  - Department of Clinical Biochemistry and Pharmacology, The Faculty of Health 
      Sciences, Ben-Gurion University of the Negev , P.O. Box 653, Beer Sheva 84105, 
      Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151202
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
SB  - IM
MH  - Drug Delivery Systems/*methods
MH  - Humans
MH  - Nanoparticles
MH  - Organelles
OTO - NOTNLM
OT  - barriers for subcellular targeting
OT  - decoration with targeting residues
OT  - drug delivery systems
OT  - exaggerated claims
OT  - limited targeting efficiency
OT  - subcellular drug targeting
EDAT- 2015/11/21 06:00
MHDA- 2016/10/01 06:00
CRDT- 2015/11/21 06:00
PHST- 2015/11/21 06:00 [entrez]
PHST- 2015/11/21 06:00 [pubmed]
PHST- 2016/10/01 06:00 [medline]
AID - 10.1021/acs.molpharmaceut.5b00697 [doi]
PST - ppublish
SO  - Mol Pharm. 2016 Jan 4;13(1):1-7. doi: 10.1021/acs.molpharmaceut.5b00697. Epub 
      2015 Dec 2.