کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9774678 | 1509092 | 2005 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Substantial increases in idarubicin plasma concentration by liposome encapsulation mediates improved antitumor activity
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کلمات کلیدی
DSPEHBSDAPCDSPCdpmMRTMLVIDADBPCCryo-TEMH2SO4HEPESMPPCEPCDOXQELSSDSDMEMQuasielastic light scatteringAML1,2-distearoyl-sn-glycero-3-phosphatidylcholineincrease in life spanAUC - AUChepes buffered saline - hepes بافر شورMTT - MTTN-[2-hydroxyethyl]piperazine-N′-[2-ethanesulfonic acid] - N- [2-hydroxyethyl] piperazine-N '- [2-ethanesulfonic acid]ILS - آنهاsphingomyelin - اسفنگومیلینsulphuric acid - اسید سولفوریکIdarubicin - ایداروبیسینRemote loading - بارگذاری از راه دورlarge unilamellar vesicle - بزرگ کیسه بیضهdisintegrations per minute - تخریب در دقیقهegg phosphatidylcholine - تخم مرغ فسفاتیدیل کولینVolume of distribution - حجم توزیعPhase transition temperature - دمای انتقال فازDoxorubicin - دوکسوروبیسینsodium dodecyl sulphate - سدیم دودسیل سولفاتpharmacokinetic - فارماکوکینتیکphosphatidylcholine - فسفاتیدیل کولینphosphatidylethanolamine - فسفاتیدیلتانولامینAcute myelogenous leukemia - لوسمی حادمیولوزLUV - لووLiposomes - لیپوزومDulbecco's Modified Essential Medium - متوسط ضروری اصلاح شده Dulbeccoarea under the curve - منطقه تحت منحنیMean residence time - میانگین زمان اقامتcryo-transmission electron microscopy - میکروسکوپ الکترونی کریو انتقالMultilamellar vesicle - پاپیون چندگانهPoly(ethylene glycol) - پلی اتیلن گلایکول PEG - پلیاتیلن گلیکول cholesterol - کلسترولCHE - کهpH gradient - گرادیان pH
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی مواد
بیومتریال
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Idarubicin has been successfully encapsulated in cholesterol-free liposomes, however, little is known about how the rate of drug release from circulating liposomes influences therapeutic activity. The studies described herein assess the attributes of a liposome formulation required to significantly increase the plasma levels of idarubicin and further establish whether increases in the circulation longevity of the drug mediate improved antitumor activity. Pharmacokinetic assessments of 6 different 3[H]-labelled liposome formulations were compared to free idarubicin. The highest idarubicin plasma concentrations were observed with DSPC/DSPE-PEG2000 liposomes formulated with 2 mol% DSPE-PEG2000 and 150 mM (iso-osmotic) internal citrate concentration. It was shown that increased levels of PEG-lipid incorporation augmented IDA release and the optimal liposomal formulation needed to be prepared under iso-osmotic conditions. For efficacy studies in a murine leukemia model, groups of 12-14 mice were treated i.v. with saline or equivalent doses (1, 2, 3 mg/kg) of free or liposomal IDA. Liposomal treatment groups exhibited a higher % increase in life span (ILS) as compared to equivalent doses of free drug. Efficacy studies completed in two drug resistant models, P388/ADR and MDA435LCC6/MDR1, demonstrated that neither the free nor liposomal formulation of idarubicin was therapeutically active. Encapsulation of IDA in liposomes increased antitumor activity in an IDA sensitive model, however, the significant increase in plasma drug levels was not sufficient to overcome multidrug resistance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 105, Issues 1â2, 20 June 2005, Pages 89-105
Journal: Journal of Controlled Release - Volume 105, Issues 1â2, 20 June 2005, Pages 89-105
نویسندگان
Nancy Dos Santos, Dawn Waterhouse, Dana Masin, Paul G. Tardi, Göran Karlsson, Katarina Edwards, Marcel B. Bally,