کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10229494 538 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A brain-vectored angiopep-2 based polymeric micelles for the treatment of intracranial fungal infection
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
A brain-vectored angiopep-2 based polymeric micelles for the treatment of intracranial fungal infection
چکیده انگلیسی
One of the most common life-threatening infections in immunosuppressive patients, like AIDs patients, is cryptococcal meningitis or meningoencephalitis. Current therapeutic options are mostly ineffective and mortality rates remain high. Hydrophobic antifungal drug Amphotericin B (AmB), has become a golden standard in severe systemic fungal infection therapy. However, most AmB commercial formulations, including deoxycholate AmB and lipid formulations of AmB, show poor penetration into the CNS and difficulty to reach the therapeutic levels. To improve the CNS permeability of AmB, we have successfully developed an effective brain-targeting polymeric micellar system with angiopep-2 modified, named Angiopep-PEG-PE/AmB polymeric micelles. An immunosuppressive murine model with Cryptococcus neoformans meningoencephalitis (CNME) was established to evaluate the CNS penetration efficiency and antifungal treatment efficacy of the AmB-incorporated brain-vectored polymeric micellar formulation, compared with the AmB commercial formulations. After three consecutive days of i.v. administration, the results showed that the group treated with Angiopep-PEG-PE/AmB achieved the greatest treatment efficacy, which reached the highest AmB level in brain, reduced the brain fungal burden significantly, decreased histopathological severity and prolonged the median survival time. The increased treatment efficacy could be attributed to the brain-targeting delivery system promoted AmB crossing the BBB and penetrating into the brain to reach the therapeutic concentration. The underlying mechanism was also explored in this work. Therefore, the brain-targeting delivery system could have potential and promising implications for treatment of intracerebral fungal infection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 33, Issue 28, October 2012, Pages 6898-6907
نویسندگان
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