PMID- 23905970
OWN - NLM
STAT- MEDLINE
DCOM- 20140220
LR  - 20151119
IS  - 1091-7691 (Electronic)
IS  - 0895-8378 (Linking)
VI  - 25
IP  - 9
DP  - 2013 Aug
TI  - In vitro and ex vivo toxicological testing of sildenafil-loaded solid lipid 
      nanoparticles.
PG  - 536-43
LID - 10.3109/08958378.2013.810315 [doi]
AB  - The aim of this study was to investigate the potential cytotoxicity of solid 
      lipid nanoparticles (SLN) loaded with sildenafil. The SLNs were tested as a new 
      drug delivery system (DDS) for the inhalable treatment of pulmonary hypertension 
      in human lungs. Solubility of sildenafil in SLN lipid matrix (30:70 
      phospholipid:triglyceride) was determined to 1% sildenafil base and 0.1% 
      sildenafil citrate, respectively. Sildenafil-loaded SLN with particle size of 
      approximately 180 nm and monomodal particle size distribution were successfully 
      manufactured using a novel microchannel homogenization method and were stable up 
      to three months. Sildenafil-loaded SLN were then used in in vitro and ex vivo 
      models representing lung and heart tissue. For in vitro models, human alveolar 
      epithelial cell line (A459) and mouse heart endothelium cell line (MHEC5-T) were 
      used. For ex vivo models, rat precision cut lung slices (PCLS) and rat heart 
      slices (PCHS) were used. All the models were treated with plain SLN and 
      sildenafil-loaded SLN in a concentration range of 0-5000 microg/ml of lipid matrix. 
      The toxicity was evaluated in vitro and ex vivo by 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Median 
      lethal dose 50% (LD50) values for A549 cells and PCLS were found to be in the 
      range of 1200-1900 microg/ml while for MHEC5-T cells and precision cut heart slices 
      values were found between 1500 and 2800 microg/ml. PCHS showed slightly higher LD50 
      values in comparison to PCLS. Considering the toxicological aspects, 
      sildenafil-loaded SLN could have potential in the treatment of pulmonary 
      hypertension via inhalation route.
FAU - Paranjpe, M
AU  - Paranjpe M
AD  - Institut fur Pharmazeutische Technologie, TU Braunschweig, Braunschweig, Germany.
FAU - Neuhaus, V
AU  - Neuhaus V
FAU - Finke, J H
AU  - Finke JH
FAU - Richter, C
AU  - Richter C
FAU - Gothsch, T
AU  - Gothsch T
FAU - Kwade, A
AU  - Kwade A
FAU - Buttgenbach, S
AU  - Buttgenbach S
FAU - Braun, A
AU  - Braun A
FAU - Muller-Goymann, C C
AU  - Muller-Goymann CC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Inhal Toxicol
JT  - Inhalation toxicology
JID - 8910739
RN  - 0 (Drug Carriers)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfones)
RN  - 0 (Triglycerides)
RN  - 0 (phospholipon 90G)
RN  - BW9B0ZE037 (Sildenafil Citrate)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Drug Carriers/chemistry/*toxicity
MH  - Female
MH  - Humans
MH  - In Vitro Techniques
MH  - Lung/drug effects/pathology
MH  - Mice
MH  - Myocardium/pathology
MH  - Nanoparticles/chemistry/*toxicity
MH  - Phosphatidylcholines/chemistry
MH  - Phosphodiesterase 5 Inhibitors/chemistry/*toxicity
MH  - Piperazines/chemistry/*toxicity
MH  - Purines/chemistry/toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Sildenafil Citrate
MH  - Solubility
MH  - Sulfones/chemistry/*toxicity
MH  - Triglycerides/chemistry
EDAT- 2013/08/03 06:00
MHDA- 2014/02/22 06:00
CRDT- 2013/08/03 06:00
PHST- 2013/08/03 06:00 [entrez]
PHST- 2013/08/03 06:00 [pubmed]
PHST- 2014/02/22 06:00 [medline]
AID - 10.3109/08958378.2013.810315 [doi]
PST - ppublish
SO  - Inhal Toxicol. 2013 Aug;25(9):536-43. doi: 10.3109/08958378.2013.810315.