کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487255 | 1114410 | 2008 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Passive Transfer of Polyethylene Glycol to Liposomal-Recombinant Human FVIII Enhances its Efficacy in a Murine Model for Hemophilia A
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کلمات کلیدی
rFVIIa, recombinant factor VIIaACD, Acid citrate dextrose - ACD، اسید سیترات دکستروزDMPC, dimyristoylphosphatidylcholine - DMPC، dimyristoylphosphatidylcholinePB, phosphate buffer - PB، بافر فسفاتRES, reticuloendothelial system - RES، سیستم reticuloendothelialTB, Tris buffer - TB، Tris bufferBSA, bovine serum albumin - آلبومین سرم گاویInhibitory antibodies - آنتیبادیهای مهارکنندهImmunogenicity - ایمنی زاییELISA, enzyme-linked immunosorbent assay - تست الیزاaPTT, activated partial thromboplastin time - زمان ترومبوپلاستین نسبی فعالPE, phosphatidylethanolamine - فسفاتیدیل اتانل آمینPS, phosphatidylserine - فسفاتیدیل سرینPC, phosphatidylcholine - فسفاتیدیل کولینHemophilia A - هموفیلی AIg, immunoglobulin - پادتَن یا آنتیبادی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The replacement therapy using recombinant human FVIII (rFVIII) is the first line of therapy for hemophilia A. Approximately 15-30% of the patients develop inhibitory antibodies. Recently, we reported that liposomes composed of phosphatidylserine (PS) could reduce the immunogenicity of rFVIII. However, PS containing liposomal-rFVIII is likely to reduce the systemic exposure and efficacy of FVIII due to rapid uptake of the PS containing liposomes by the reticuloendothelial system (RES). Here, we investigated whether phosphatidylserine (PS) liposomes containing Polyethylene glycol (PEG) (PEGylated), could reduce the immunogenicity of rFVIII and reverse the reduction in systemic exposure of rFVIII. Animals given PEGylated liposomal-rFVIII had lower total and inhibitory anti-rFVIII antibody titers, compared to animals treated with rFVIII alone. The mean stimulation index of CD4+ T-cells from animals given PEGylated liposomal-rFVIII also was lower than for animals that were given rFVIII alone. Pharmacokinetic studies following intravenous dosing indicated that the systemic exposure (area under the activity curve, AUAC0-24h) of PEGylated liposomal-rFVIII was ~59 IU/mLâÃâh and significantly higher than that of non-PEGylated liposomal-rFVIII (AUAC0-24hâ~â36 IU/mLâÃâh). Based on these studies, we speculate that PEGylated PS-containing liposomal rFVIII may improve efficacy of rFVIII.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 9, September 2008, Pages 3753-3764
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 9, September 2008, Pages 3753-3764
نویسندگان
Karthik Ramani, Vivek Purohit, Razvan Miclea, Puneet Gaitonde, Robert M. Straubinger, Sathy V. Balu-Iyer,