PMID- 29663290
OWN - NLM
STAT- MEDLINE
DCOM- 20180903
LR  - 20181202
IS  - 1530-9932 (Electronic)
IS  - 1530-9932 (Linking)
VI  - 19
IP  - 4
DP  - 2018 May
TI  - Pulmonary Administration of Microparticulate Antisense Oligonucleotide (ASO) for 
      the Treatment of Lung Inflammation.
PG  - 1908-1919
LID - 10.1208/s12249-018-1002-7 [doi]
AB  - Targeted delivery to the lung for controlling lung inflammation is an area that 
      we have explored in this study. The purpose was to use microparticles containing 
      an antisense oligonucleotide (ASO) to NF-kappaB to inhibit the production of 
      proinflammatory cytokines. Microparticles were prepared using the B-290 Buchi 
      Spray Dryer using albumin as the microparticle matrix. Physicochemical 
      characterization of the microparticles showed the size ranged from 2 to 5 mum, the 
      charge was - 38.4 mV, and they had a sustained release profile over 72 h. Uptake 
      of FITC-labeled ASO-loaded microparticles versus FITC-labeled ASO solution by 
      RAW264.7 murine macrophage cells was 5-10-fold higher. After pulmonary delivery 
      of microparticles to Sprague-Dawley rats, the microparticles were uniformly 
      distributed throughout the lung and were retained in the lungs until 48 h. Serum 
      cytokine (TNF-alpha and IL-1beta) levels of rats after induction of lung inflammation by 
      lipopolysaccharide were measured until 72 h. Animals receiving ASO-loaded 
      microparticles were successful in significantly controlling lung inflammation 
      during this period as compared to animals receiving no treatment. This study was 
      successful in proving that microparticulate ASO therapy was capable of 
      controlling lung inflammation.
FAU - Ubale, Ruhi V
AU  - Ubale RV
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 
      3001 Mercer University Drive, Atlanta, Georgia, 30341, USA.
FAU - Shastri, Prathap Nagaraja
AU  - Shastri PN
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 
      3001 Mercer University Drive, Atlanta, Georgia, 30341, USA.
FAU - Oettinger, Carl
AU  - Oettinger C
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 
      3001 Mercer University Drive, Atlanta, Georgia, 30341, USA.
FAU - D'Souza, Martin J
AU  - D'Souza MJ
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 
      3001 Mercer University Drive, Atlanta, Georgia, 30341, USA. dsouza_mj@mercer.edu.
LA  - eng
PT  - Journal Article
DEP - 20180416
PL  - United States
TA  - AAPS PharmSciTech
JT  - AAPS PharmSciTech
JID - 100960111
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Oligonucleotides, Antisense)
SB  - IM
MH  - Animals
MH  - Drug Delivery Systems/*methods
MH  - Female
MH  - Lipopolysaccharides/toxicity
MH  - Lung/*drug effects/metabolism/pathology
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - *Microspheres
MH  - Oligonucleotides, Antisense/*administration & dosage/metabolism
MH  - Pneumonia/chemically induced/*drug therapy/metabolism
MH  - RAW 264.7 Cells
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - antisense oligonucleotide
OT  - inflammation
OT  - microparticles
OT  - pulmonary delivery
OT  - spray drying
EDAT- 2018/04/18 06:00
MHDA- 2018/09/04 06:00
CRDT- 2018/04/18 06:00
PHST- 2017/09/12 00:00 [received]
PHST- 2018/03/19 00:00 [accepted]
PHST- 2018/04/18 06:00 [pubmed]
PHST- 2018/09/04 06:00 [medline]
PHST- 2018/04/18 06:00 [entrez]
AID - 10.1208/s12249-018-1002-7 [pii]
AID - 10.1208/s12249-018-1002-7 [doi]
PST - ppublish
SO  - AAPS PharmSciTech. 2018 May;19(4):1908-1919. doi: 10.1208/s12249-018-1002-7. Epub 
      2018 Apr 16.