PMID- 19000726
OWN - NLM
STAT- MEDLINE
DCOM- 20090305
LR  - 20211020
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 133
IP  - 3
DP  - 2009 Feb 10
TI  - Delivery of rapamycin to dendritic cells using degradable microparticles.
PG  - 191-7
LID - 10.1016/j.jconrel.2008.10.011 [doi]
AB  - Degradable microparticles have the potential to protect and release drugs over 
      extended periods and, if sized appropriately, can be passively targeted to 
      phagocytic cells in vivo. Dendritic cells (DC) are a class of phagocytic cells 
      known to play important roles in transplant rejection. Previously, we have 
      demonstrated that DC treated with an immunosuppressive drug, rapamycin, have the 
      ability to suppress transplant rejection. Herein, we describe a strategy to 
      deliver an intracellular depot of rapamycin to DC. To achieve this, rapamycin was 
      encapsulated into ~3.4 microm sized poly(lactic-co-glycolic)acid (PLGA) 
      microparticles (rapaMPs), and release behavior was examined under 
      intra-phagosomal (pH=5) and extracellular (pH=7.4) conditions. It was observed 
      that 4 days following phagocytosis of rapaMP, DC have significantly reduced 
      ability to activate T cells, in comparison to DC treated with soluble rapamycin. 
      Hence, we conclude that DC-specific intracellular delivery of rapamycin results 
      in better efficacy of the drug, with respect to its ability to modulate DC 
      function, when compared to treating DC with extracellular rapamycin.
FAU - Jhunjhunwala, S
AU  - Jhunjhunwala S
AD  - Department of Bioengineering, University of Pittsburgh, PA 15260, USA.
FAU - Raimondi, G
AU  - Raimondi G
FAU - Thomson, A W
AU  - Thomson AW
FAU - Little, S R
AU  - Little SR
LA  - eng
GR  - KL2 RR024154-02/RR/NCRR NIH HHS/United States
GR  - R01 AI060994/AI/NIAID NIH HHS/United States
GR  - KL2 RR024154/RR/NCRR NIH HHS/United States
GR  - AI 67541/AI/NIAID NIH HHS/United States
GR  - KL2 TR000146/TR/NCATS NIH HHS/United States
GR  - KL2 RR024154-04/RR/NCRR NIH HHS/United States
GR  - AI 60994/AI/NIAID NIH HHS/United States
GR  - R01 AI067541/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081026
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - B7-2 Antigen/metabolism
MH  - Biological Availability
MH  - CD4-Positive T-Lymphocytes/cytology/drug effects/immunology
MH  - CD40 Antigens/metabolism
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Dendritic Cells/*drug effects/physiology
MH  - Drug Delivery Systems/*methods
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Lactic Acid/chemistry
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron, Scanning
MH  - Microspheres
MH  - Particle Size
MH  - Phagocytosis/drug effects
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Sirolimus/*administration & dosage/pharmacokinetics/pharmacology
MH  - Surface Properties
PMC - PMC2925512
MID - NIHMS186476
EDAT- 2008/11/13 09:00
MHDA- 2009/03/06 09:00
PMCR- 2010/08/23
CRDT- 2008/11/13 09:00
PHST- 2008/07/07 00:00 [received]
PHST- 2008/09/24 00:00 [revised]
PHST- 2008/10/06 00:00 [accepted]
PHST- 2008/11/13 09:00 [pubmed]
PHST- 2009/03/06 09:00 [medline]
PHST- 2008/11/13 09:00 [entrez]
PHST- 2010/08/23 00:00 [pmc-release]
AID - S0168-3659(08)00635-4 [pii]
AID - 10.1016/j.jconrel.2008.10.011 [doi]
PST - ppublish
SO  - J Control Release. 2009 Feb 10;133(3):191-7. doi: 10.1016/j.jconrel.2008.10.011. 
      Epub 2008 Oct 26.