Preparation and stability of lipid-coated nanocapsules of cisplatin: anionic phospholipid specificity
| Autor: | Maria J. Velinova, Willem J. M. Mulder, Rutger W.H.M. Staffhorst, Anton I.P.M. de Kroon, Bart A. J. Jansen, Ben de Kruijff, Arno S Dries |
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| Rok vydání: | 2004 |
| Předmět: |
Anions
Nanocapsule Drug Compounding Phospholipid Biophysics Antineoplastic Agents Capsules Biochemistry Nanocapsules Anionic phospholipid chemistry.chemical_compound Mice Lipid formulation Drug Stability Phosphatidylcholine Cell Line Tumor Freezing medicine Animals Humans Nanotechnology Lipid bilayer Phospholipids Cisplatin Phosphatidylethanolamine Bilayer Temperature Water Phosphatidic acid Cell Biology chemistry Drug delivery Stability medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1663(1-2):135-142 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/j.bbamem.2004.03.002 |
| Popis: | Cisplatin nanocapsules represent a novel lipid formulation of the anti-cancer drug cis-diamminedichloroplatinum(II) (cisplatin), in which nanoprecipitates of cisplatin are coated by a phospholipid bilayer consisting of a 1:1 mixture of zwitterionic phosphatidylcholine (PC) and negatively charged phosphatidylserine (PS). Cisplatin nanocapsules are characterized by an unprecedented cisplatin-to-lipid ratio and exhibit increased in vitro cytotoxicity compared to the free drug [Nat. Med. 8, (2002) 81]. In the present study, the stability of the cisplatin nanocapsules was optimized by varying the lipid composition of the bilayer coat and monitoring in vitro cytotoxicity and the release of contents during incubations in water and in mouse serum. The release of cisplatin from the PC/PS (1:1) nanocapsules in water increased with increasing temperature with a t(1/2) of 6.5 h at 37 degrees C. At 4 degrees C, cisplatin was retained in the nanocapsules for well over 8 days. Replacement of PS by either phosphatidylglycerol or phosphatidic acid revealed that nanocapsules prepared of PS were more stable, which was found to be due to the ability of PS to form a stable cisplatin-PS coordination complex. Mouse serum had a strong destabilizing effect on the cisplatin nanocapsules. The PC/PS formulation lost over 80% of cisplatin within minutes after resuspension in serum. Incorporation of poly(ethylene glycol 2000) (PEG)-derivatized phosphatidylethanolamine and cholesterol in the bilayer coat extended the lifetime of the cisplatin nanocapsules in mouse serum to almost an hour. The results demonstrate that specificity in the interaction of cisplatin with anionic phospholipids is an important criterium for the formation and stability of cisplatin nanocapsules. |
| Databáze: | OpenAIRE |
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