PMID- 21883921
OWN - NLM
STAT- MEDLINE
DCOM- 20120329
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 11
IP  - 12
DP  - 2011 Dec
TI  - Nanoparticle delivery of mycophenolic acid upregulates PD-L1 on dendritic cells 
      to prolong murine allograft survival.
PG  - 2582-92
LID - 10.1111/j.1600-6143.2011.03725.x [doi]
AB  - Conventional immunosuppressive drug delivery requires high systemic drug levels 
      to provide therapeutic benefit, but frequently results in toxic side effects. 
      Novel drug delivery methods, such as FDA-approved poly(lactic-co-glycolic acid) 
      (PLGA) nanoparticles (NPs), are promising drug delivery platforms to reduce drug 
      doses and minimize toxicity. Using murine models of skin transplantation, we 
      investigated whether PLGA NPs would effectively deliver mycophenolic acid (MPA), 
      a common clinical immunosuppressant, and avoid the toxicity of conventional drug 
      delivery. We found that intermittent treatment with NPs encapsulated with MPA 
      (NP-MPA) resulted in a significant extension of allograft survival than 
      intermittent conventional MPA treatment even though the concentration of MPA 
      within NP-MPA was a 1000-fold lower than conventional drug. Importantly, 
      recipients who were administered NP-MPA intermittently avoided drug toxicity, 
      whereas those treated with daily conventional drug manifested cytopenias. 
      Dendritic cells (DCs) endocytosed NP-MPA to upregulate programmed death ligand-1 
      (PD-L1) and displayed a decreased ability to prime alloreactive T cells. 
      Importantly, the ability of NP-MPA to promote allograft survival was partly PD-L1 
      dependent. Collectively, this study indicates that NPs are potent drug delivery 
      tools that extend allograft survival without drug toxicity.
CI  - (c)Copyright 2011 The American Society of Transplantation and the American Society 
      of Transplant Surgeons.
FAU - Shirali, A C
AU  - Shirali AC
AD  - Department of Internal Medicine and Immunobiology, Yale University, New Haven, 
      CT, USA.
FAU - Look, M
AU  - Look M
FAU - Du, W
AU  - Du W
FAU - Kassis, E
AU  - Kassis E
FAU - Stout-Delgado, H W
AU  - Stout-Delgado HW
FAU - Fahmy, T M
AU  - Fahmy TM
FAU - Goldstein, D R
AU  - Goldstein DR
LA  - eng
GR  - AG033049/AG/NIA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110830
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Cd274 protein, mouse)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/administration & dosage/pharmacokinetics
MH  - B7-H1 Antigen/*metabolism
MH  - Cells, Cultured
MH  - Combined Modality Therapy
MH  - Dendritic Cells/*drug effects/metabolism
MH  - *Drug Delivery Systems
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Graft Survival/*drug effects
MH  - Lactic Acid/chemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mycophenolic Acid/*administration & dosage/pharmacokinetics
MH  - Nanoparticles/*chemistry
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Skin Diseases/immunology/mortality/*therapy
MH  - Skin Transplantation
MH  - Survival Rate
MH  - Tissue Distribution
MH  - Transplantation, Homologous
EDAT- 2011/09/03 06:00
MHDA- 2012/03/30 06:00
CRDT- 2011/09/03 06:00
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2012/03/30 06:00 [medline]
AID - S1600-6135(22)28188-X [pii]
AID - 10.1111/j.1600-6143.2011.03725.x [doi]
PST - ppublish
SO  - Am J Transplant. 2011 Dec;11(12):2582-92. doi: 10.1111/j.1600-6143.2011.03725.x. 
      Epub 2011 Aug 30.