PMID- 30342174
OWN - NLM
STAT- MEDLINE
DCOM- 20190415
LR  - 20190415
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 127
DP  - 2019 Jan 15
TI  - Comparison of the in vitro cytotoxicity among phospholipid-based parenteral drug 
      delivery systems: Emulsions, liposomes and aqueous lecithin dispersions (WLDs).
PG  - 92-101
LID - S0928-0987(18)30465-2 [pii]
LID - 10.1016/j.ejps.2018.10.018 [doi]
AB  - Lecithin and isolated phospholipids (mainly phosphatidylcholine) have been used 
      for years as pharmaceutical excipients in parenteral formulations: submicron 
      emulsions, liposomes and mixed micelles. Under development are also other 
      lecithin-based drug delivery systems, e.g. aqueous lecithin dispersions (WLDs). 
      The aim of the study was to investigate the properties and potential cytotoxicity 
      of 7 different phospholipid-based dispersions intended for parenteral 
      administration: emulsions, liposomes and WLDs. Each formulation contained egg 
      phosphatidylcholine (PC) in the concentration range of 0.6-5.0%, and to some 
      formulations other surfactants, such as polysorbate 80 (P80), Solutol HS 15 (HS) 
      and cholesterol (Ch) were added. Particles in all dispersions were homogenous 
      (PDI < 0.26) and submicron in size (Z-average in the range of approx. 
      100-260 nm). The cytotoxicity of all tested formulations was evaluated by means 
      of 3 independent methods: a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium 
      bromide (MTT) assay, a real-time xCELLigence (RTCA) system, and a flow cytometry 
      analysis, using two cell lines: human embryonic kidney 293 (HEK-293) and human 
      promyelocytic leukaemia (HL-60). The results indicated that regardless of the 
      test method and cell line type, the cytotoxicity of all formulations was low, 
      especially when dispersions diluted to concentrations of =10% were tested. A more 
      pronounced cytotoxic effect was noticed only for the following formulations: 
      E-P80 (emulsion containing P80), WLD (unbuffered aqueous lecithin dispersion) and 
      L-Ch (liposomes containing Ch), tested as less diluted (concentration 10% or 
      25%). IC50 values measured for these dispersions (on HL-60 cells) amounted to: 
      10.4 +/- 0.5% (v/v), 14.4 +/- 0.2% (v/v) and 24.2 +/- 0.6% (v/v), respectively. Our 
      investigation confirmed the biocompatibility of all tested phospholipid-based 
      formulations: emulsions, liposomes and also newly-developed WLDs, which can be 
      considered as safe parenteral drug carriers.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Placzek, Marcin
AU  - Placzek M
AD  - Department of Pharmaceutical Technology, Medical University of Gdansk, al. gen. 
      J. Hallera 107, 80-416 Gdansk, Poland. Electronic address: mpl@gumed.edu.pl.
FAU - Watrobska-Swietlikowska, Dorota
AU  - Watrobska-Swietlikowska D
AD  - Department of Pharmaceutical Technology, Medical University of Gdansk, al. gen. 
      J. Hallera 107, 80-416 Gdansk, Poland.
FAU - Stefanowicz-Hajduk, Justyna
AU  - Stefanowicz-Hajduk J
AD  - Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, 
      al. gen. J. Hallera 107, 80-416 Gdansk, Poland.
FAU - Drechsler, Markus
AU  - Drechsler M
AD  - Bavarian Polymer Institute (BPI), Key Lab of Electron and Optical Microscopy, 
      University of Bayreuth, Universitaetsstr. 30, 95440 Bayreuth, Germany.
FAU - Ochocka, Jadwiga Renata
AU  - Ochocka JR
AD  - Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, 
      al. gen. J. Hallera 107, 80-416 Gdansk, Poland.
FAU - Sznitowska, Malgorzata
AU  - Sznitowska M
AD  - Department of Pharmaceutical Technology, Medical University of Gdansk, al. gen. 
      J. Hallera 107, 80-416 Gdansk, Poland.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20181017
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Emulsions)
RN  - 0 (Liposomes)
RN  - 0 (Phospholipids)
RN  - 0 (Surface-Active Agents)
SB  - IM
MH  - Cell Survival/drug effects
MH  - *Drug Delivery Systems
MH  - Emulsions
MH  - HEK293 Cells
MH  - HL-60 Cells
MH  - Humans
MH  - Liposomes
MH  - Parenteral Nutrition
MH  - *Phospholipids/administration & dosage/chemistry
MH  - *Surface-Active Agents/administration & dosage/chemistry
OTO - NOTNLM
OT  - Flow cytometry analysis
OT  - Lecithin
OT  - MTT assay
OT  - Phospholipid dispersions
OT  - RTCA system
OT  - Surfactants
EDAT- 2018/10/21 06:00
MHDA- 2019/04/16 06:00
CRDT- 2018/10/21 06:00
PHST- 2018/02/16 00:00 [received]
PHST- 2018/09/12 00:00 [revised]
PHST- 2018/10/16 00:00 [accepted]
PHST- 2018/10/21 06:00 [pubmed]
PHST- 2019/04/16 06:00 [medline]
PHST- 2018/10/21 06:00 [entrez]
AID - S0928-0987(18)30465-2 [pii]
AID - 10.1016/j.ejps.2018.10.018 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2019 Jan 15;127:92-101. doi: 10.1016/j.ejps.2018.10.018. Epub 
      2018 Oct 17.