Development and characterization of liposomal formulations for rapamycin delivery and investigation of their antiproliferative effect on MCF7 cells

Rouf, M.A. | Vural, I. | Renoir, J.M. | Hincal, A.A.

Article | 2009 | Journal of Liposome Research19 ( 4 ) , pp.322 - 331

Rapamycin (Sirolimus) is a macrolide lactone with antifungal, immunosuppressant, and antiproliferative actions. The mechanism of rapamycin action involves the inhibition of mTOR and subsequent cytostasis. Rapamycin also prevents angiogenesis in tumors and can prevent cancer cells' resistance to other chemotherapeutic agents. However, very poor water solubility, bioavailability, only slight solubility in acceptable parenteral excipients, chemical instability, and major sequestration (95%) of free rapamycin into the erythrocytes have prevented its development as an anticancer drug. To address these problems, it was attempted to develo . . .p liposomal rapamycin delivery systems in this study. Conventional and pegylated liposomes were prepared with various lipid and cholesterol ratios. They were then characterized; these liposomes contained 0.680.90mg of rapamycin per milliliter of liposome suspension. Having suitable particle size, these liposomes successfully retained the entrapped drug. Both types of liposomes were found to be effective; however, conventional liposomes showed better antiproliferative activity against MCF-7 cells than pegylated liposomes. But, pegylated liposome showed better stability than conventional liposomes. In conclusion, the enhanced permeability and retention effercts of tumors should provide the opportunity for pegylated liposomal rapamycin to be applied as an intravenous drug-delivery system for targeted delivery to cancer cells, avoiding the major sequestration of free rapamycin into the erythrocytes Daha fazlası Daha az

Quantitative diffusion-weighted magnetic resonance imaging of normal and diseased uterine zones

Kilickesmez, O. | Bayramoglu, S. | Inci, E. | Cimilli, T. | Kayhan, A.

Article | 2009 | Acta Radiologica50 ( 3 ) , pp.340 - 347

Background: Magnetic resonance (MR) imaging has been established as the best imaging modality for the detection, localization, and staging of uterine cancers. Recently, the usefulness of diffusion-weighted imaging (DWI) in the diagnosis of cancers has been reported in several studies. Purpose: To calculate the apparent diffusion coefficient (ADC) values of normal uterine zones as well as benign and malignant uterine diseases, and to determine a cut-off ADC value for the quantitative detection of uterine malignancies with DWI. Material and Methods: Eighty-seven patients (mean age 53 years) with 107 benign and malignant uterine pathol . . .ogies and 50 healthy controls (mean age 38 years) were enrolled in the study. DWI was performed with b factors of 0, 500, and 1000 s/mm2. Results: The ADC values of benign and malignant lesions were compared using Student's t test. The mean and the standard deviation of the ADC values of the control group were as follows: myometrium 1.760.1910-3 mm2/s, junctional zone 0.990.1810-3 mm2/s, endometrium 1.650.3310-3 mm2/s, and cervix 1.710.1710-3 mm2/s. There was a statistically significant difference among the ADC values of normal myometrium and leiomyomas (1.470.3610-3 mm2/s; P0.009), endometrium and endometrial carcinomas (0.860.1310-3 mm2/s; P0.001), myometrium-junctional zone and adenomyosis (1.240.2010-3mm2/s; P0.001), and cervix and cervical carcinomas (0.910.1410-3 mm2/s; P0.001). The ADC values differed significantly between malignant (0.880.11) and benign lesions (1.550.33; P0.01). A cut-off value for malignant lesions of 1.0510-3 mm2/s yielded a sensitivity, specificity, and accuracy of 95.83%, 94.55%, and 94.94%, respectively. Conclusion: The present study shows that ADC measurements have the potential to quantitatively differentiate between normal and cancerous tissues of the uterine zones. We propose adding DWI as an adjunct sequence in the MR protocol for the assessment of uterine lesions. © 2009 Informa UK Ltd Daha fazlası Daha az

6698 sayılı Kişisel Verilerin Korunması Kanunu kapsamında yükümlülüklerimiz ve çerez politikamız hakkında bilgi sahibi olmak için alttaki bağlantıyı kullanabilirsiniz.

Bu site altında yer alan tüm kaynaklar Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.