کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10613506 | 986891 | 2005 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Encapsulation of doxorubicin into thermosensitive liposomes via complexation with the transition metal manganese
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کلمات کلیدی
CHOLmonosialogangliosidePEG-lipidsDPPGMSPCMPPCCryo-TEMDSPE-PEG2000DSPCHBSGM1dMPCDPPC1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine - 1-پالمیتویل-2-هیدروکسی-اس-گلیسرو-3-فسفوکلین1,2-dimyristoyl-sn-glycero-3-phosphocholine - 1،2-dimyristoyl-sn-glycero-3-phosphosocholine1,2-dipalmitoyl-sn-glycero-3-phosphocholine - 1،2-dipalmitoyl-sn-glycero-3-phosphocholine1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol - 1،2-dipalmitoyl-sn-glycero-3-phosphoglycerol1,2-distearoyl-sn-glycero-3-phosphocholine - 1،2-distearoyl-sn-glycero-3-phosphocholineHEPES-buffered saline - HEPES-Buffered salineMRI - امآرآی یا تصویرسازی تشدید مغناطیسیSHE - اوMagnetic resonance imaging - تصویربرداری رزونانس مغناطیسیcryo-transmission electron microscopy - میکروسکوپ الکترونی کریو انتقالcholesterol - کلسترولCHE - که
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی مواد
بیومتریال
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
In the present study, doxorubicin was encapsulated into two thermosensitive liposome formulations which were composed of DPPC / MSPC / DSPE-PEG2000 (90 / 10 / 4 mole ratio) or DPPC/DSPE-PEG2000 (95/5 mole ratio). Doxorubicin loading was achieved through the use of a pH gradient or a novel procedure that involved doxorubicin complexation with manganese. Regardless of the initial drug-to-lipid ratios (D : L), the final D : L reached a maximum of 0.05 (w / w) when doxorubicin was encapsulated via a pH gradient for both thermosensitive liposome formulations. In contrast, the final maximum D : L achieved through manganese complexation was 0.2 (w / w), and this loading method did not affect temperature-induced drug release, with 85% of drug released from MSPC-containing liposomes within 10 min at 42 °C but < 5% released over 60 min at 37 °C. When the thermosensitive liposomes prepared via the two different loading methods were injected into mice, similar plasma elimination profiles were observed. Cryo-transmission electron microscopy analysis indicated the presence of doxorubicin fiber bundles in liposomes loaded via pH gradient, compared to a stippled and diffuse morphology in those loaded via manganese complexation. To investigate the effect of intraliposomal pH on drug precipitate morphology, the A23187 ionophore (mediates Mn2+/H+ exchange) was added to liposomes loaded with doxorubicin-manganese complex, and the stippled and diffuse appearance could be converted to one exhibiting fiber bundles after acidification of the liposome core. This suggests that the formation of doxorubicin-manganese complex is favored when the intraliposomal pH is > 6.5. During the conversion to the fiber bundle morphology, no doxorubicin release was observed when A23187 was added to liposomes exhibiting a 0.05 (w / w), whereas a significant release was noted when the initial D : L was 0.2 (w / w). Following acidification of the liposomal interior and establishment of an apparent new D : L equilibrium, the measured D : L ratio was 0.05 (w / w). In conclusion, the manganese complexation loading method increased the encapsulation efficiency of doxorubicin in thermosensitive liposomes with no major impact on temperature-triggered drug release or pharmacokinetics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 104, Issue 2, 18 May 2005, Pages 271-288
Journal: Journal of Controlled Release - Volume 104, Issue 2, 18 May 2005, Pages 271-288
نویسندگان
Gigi N.C. Chiu, Sheela A. Abraham, Ludger M. Ickenstein, Rebecca Ng, Göran Karlsson, Katarina Edwards, Ellen K. Wasan, Marcel B. Bally,