PMID- 28646511
OWN - NLM
STAT- MEDLINE
DCOM- 20180522
LR  - 20181108
IS  - 1552-4965 (Electronic)
IS  - 1549-3296 (Linking)
VI  - 105
IP  - 11
DP  - 2017 Nov
TI  - Control of autoimmune inflammation using liposomes to deliver positive allosteric 
      modulators of metabotropic glutamate receptors.
PG  - 2977-2985
LID - 10.1002/jbm.a.36151 [doi]
AB  - Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly 
      recognized as foreign and attacked by the adaptive immune system. Dendritic cells 
      (DCs) direct adaptive immunity by presenting antigens to T cells, therefore 
      serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino) 
      cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of 
      metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by 
      altering cytokine secretion to bias T cell differentiation. The therapeutic 
      potential of PHCCC, however, is hindered by dose-limiting toxicity, poor 
      solubility, and the need for frequent dosing. We hypothesized liposomal delivery 
      of PHCCC might enable safe, effective delivery of this hydrophobic drug to 
      exploit metabolism as a means of controlling inflammation in self-reactive immune 
      cells. PHCCC was readily encapsulated in liposomes modified with polyethylene 
      glycol. Under sink conditions, controlled release resulted in 58% of drug 
      released into media over 18 hours. Culture of primary DCs with PHCCC liposomes 
      reduced pro-inflammatory cytokine secretion while reducing toxicity four-fold 
      compared with soluble PHCCC. During co-culture of DCs with myelin-reactive T 
      cells from transgenic mice, PHCCC liposomes reduced T cell proliferation and 
      interferon gamma secretion. These results support the potential of using 
      liposomes to promote tolerance through biocompatible delivery of metabolic 
      modulators. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 
      2977-2985, 2017.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Gammon, Joshua M
AU  - Gammon JM
AD  - Fischell Department of Bioengineering, University of Maryland, College Park, 
      Maryland.
FAU - Adapa, Arjun R
AU  - Adapa AR
AD  - Fischell Department of Bioengineering, University of Maryland, College Park, 
      Maryland.
FAU - Jewell, Christopher M
AU  - Jewell CM
AD  - Fischell Department of Bioengineering, University of Maryland, College Park, 
      Maryland.
AD  - Department of Microbiology and Immunology, University of Maryland Medical School, 
      Baltimore, Maryland.
AD  - Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland.
AD  - University States Department of Veteran Affairs, Baltimore, Maryland.
LA  - eng
PT  - Journal Article
DEP - 20170714
PL  - United States
TA  - J Biomed Mater Res A
JT  - Journal of biomedical materials research. Part A
JID - 101234237
RN  - 0 (Benzopyrans)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Liposomes)
RN  - 0 (N-phenyl-7-(hydroxyimino)cyclopropa(b)chromen-1a-carboxamide)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - YZN9W7P1BX (metabotropic glutamate receptor 4)
SB  - IM
MH  - Allosteric Regulation/drug effects
MH  - Animals
MH  - Autoimmunity/*drug effects
MH  - Benzopyrans/*administration & dosage/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Delayed-Action Preparations/chemistry
MH  - Dendritic Cells/drug effects/immunology
MH  - Female
MH  - Inflammation/*drug therapy/immunology
MH  - Liposomes/chemistry
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, Metabotropic Glutamate/*immunology
MH  - T-Lymphocytes/*drug effects/immunology
OTO - NOTNLM
OT  - drug delivery and controlled release
OT  - liposome and nanoparticle
OT  - metabolism
OT  - tolerance and autoimmunity
OT  - vaccine and immunotherapy
EDAT- 2017/06/25 06:00
MHDA- 2018/05/23 06:00
CRDT- 2017/06/25 06:00
PHST- 2017/02/24 00:00 [received]
PHST- 2017/06/09 00:00 [revised]
PHST- 2017/06/21 00:00 [accepted]
PHST- 2017/06/25 06:00 [pubmed]
PHST- 2018/05/23 06:00 [medline]
PHST- 2017/06/25 06:00 [entrez]
AID - 10.1002/jbm.a.36151 [doi]
PST - ppublish
SO  - J Biomed Mater Res A. 2017 Nov;105(11):2977-2985. doi: 10.1002/jbm.a.36151. Epub 
      2017 Jul 14.