PMID- 11948528
OWN - NLM
STAT- MEDLINE
DCOM- 20020814
LR  - 20190711
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 91
IP  - 4
DP  - 2002 Apr
TI  - Exploitation of intracellular pH gradients in the cellular delivery of 
      macromolecules.
PG  - 903-13
AB  - Most cellular components such as the cytoplasm, endosomes, lysosomes, endoplasmic 
      reticulum, Golgi bodies, mitochondria, and nuclei are known to maintain their own 
      characteristic pH values. These pH values range from as low as 4.5 in the 
      lysosome to about 8.0 in the mitochondria. Given these proton gradients around a 
      neutral pH, weak acids, and bases with a pKa between 5.0 and 8.0 can exhibit 
      dramatic changes in physicochemical properties. These compounds can be conjugated 
      as such to macromolecules or incorporated into polymeric or liposomal 
      formulations to promote the efficient cellular delivery of macromolecules. 
      Mechanistically, the carrier molecules can facilitate favorable membrane 
      partition, membrane fusion, transient pore formation, or membrane disruption. 
      Drug carriers equipped with such pH-sensitive triggers and switches are able to 
      significantly enhance the cellular delivery of macromolecules in vitro. However, 
      the successful application of these molecules for efficient delivery in vivo 
      requires the design of noncytotoxic, nonimmunogenic, serum compatible and 
      biochemically labile carriers, systematic analysis of their mechanisms of action, 
      and extensive animal studies.
CI  - Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J 
      Pharm Sci 91: 903-913, 2002
FAU - Asokan, Aravind
AU  - Asokan A
AD  - Division of Drug Delivery & Disposition, CB # 7360, School of Pharmacy, 
      University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, 
      USA.
FAU - Cho, Moo J
AU  - Cho MJ
LA  - eng
GR  - GM50768/GM/NIGMS NIH HHS/United States
GR  - GM57557/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Drug Carriers)
RN  - 0 (Macromolecular Substances)
SB  - IM
MH  - Animals
MH  - Drug Carriers/administration & dosage/chemistry
MH  - Drug Delivery Systems/*methods
MH  - Endosomes/drug effects/physiology
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Intracellular Fluid/*drug effects/*physiology
MH  - Macromolecular Substances
MH  - Organelles/drug effects/physiology
RF  - 72
EDAT- 2002/04/12 10:00
MHDA- 2002/08/15 10:01
CRDT- 2002/04/12 10:00
PHST- 2002/04/12 10:00 [pubmed]
PHST- 2002/08/15 10:01 [medline]
PHST- 2002/04/12 10:00 [entrez]
AID - S0022-3549(16)30976-5 [pii]
AID - 10.1002/jps.10095 [doi]
PST - ppublish
SO  - J Pharm Sci. 2002 Apr;91(4):903-13. doi: 10.1002/jps.10095.