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      Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice

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          Abstract

          Amphotericin B deoxycholate (AmB), a classic antifungal drug, remains the initial treatment of choice for deep fungal infections, but it is not appropriate for treatment of cryptococcal meningitis due to its inability to pass through the blood–brain barrier (BBB). We examined the efficacy of amphotericin B-polybutylcyanoacrylate nanoparticles (AmB-PBCA-NPs) modified with polysorbate 80 that had a mean particle diameter less than 100 nanometers (69.0 ± 28.6 nm). AmB-PBCA-NPs were detected in the brain 30 minutes after systemic administration into BALB/c mice and had a higher concentration than systemically administered AmB liposome (AmB-L, P < 0.05); AmB was not detected in the brain. Following infection for 24 hours and then 7 days of treatment, the survival rate of mice in the AmB-PBCA-NP group (80%) was significantly higher than that of the AmB (0%) or AmB-L (60%) treatment groups. Fungal load was also lower when assessed by colony-forming unit counts obtained after plating infected brain tissue ( P < 0.05). Our study indicates that AmB-PBCA-NPs with polysorbate 80 coating have the capacity to transport AmB across the BBB and is an efficient treatment against cryptococcal meningitis in a mouse model.

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          Most cited references 33

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          Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles).

          Transport of the hexapeptide dalargin across the blood-brain barrier was accomplished using a nanoparticle formulation. The formulation consisted of dalargin bound to poly(butyl cyanoacrylate) nanoparticles by sorption, coated with polysorbate 80. Intravenous injection of this formulation to mice resulted in an analgesic effect. All controls, including a simple mixture of the three components (drugs, nanoparticles, and surfactant) mixed directly before i.v. injection, exhibited no effect. Analgesia was also prevented by pretreatment with naloxone. Fluorescent and electron microscopic studies indicated that the passage of the particle-bound drug occurred by phagocytic uptake of the polysorbate 80-coated nanoparticles by the brain blood vessel endothelial cells.
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            Epidemiology and clinical features of Cryptosporidium infection in immunocompromised patients.

            Cryptosporidium spp. are a major cause of diarrheal disease in both immunocompetent and immunodeficient individuals. They also cause waterborne disease in both the United States and United Kingdom. Studies on the mechanisms of immunity to cryptosporidiosis indicate the importance of the T-cell response. The spectrum and severity of disease in immunocompromised individuals with cryptosporidiosis reflect this importance since the most severe disease is seen in individuals with defects in the T-cell response. The most commonly studied group is that of patients with AIDS. These patients suffer from more severe and prolonged gastrointestinal disease that can be fatal; in addition, body systems other than the gastrointestinal tract may be affected. The widespread use of antiretroviral therapy does appear to be having a beneficial effect on recovery from cryptosporidiosis and on the frequency of infection in human immunodeficiency virus-positive patients. Other diseases that are associated with increased risk of severe cryptosporidiosis, such as primary immunodeficiencies, most notably severe combined immunodeficiency syndrome, are also predominantly associated with T-cell defects. Of the remaining groups, children with acute leukemia seem to be most at risk from cryptosporidiosis. There is less evidence of severe complications in patients with other malignant diseases or in those receiving immunosuppressive chemotherapy.
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              Polycyanoacrylate nanocapsules as potential lysosomotropic carriers: preparation, morphological and sorptive properties.

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                Author and article information

                Journal
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2011
                2011
                28 April 2011
                : 6
                : 905-913
                Affiliations
                [1 ]Institute for Laser Medicine and Biophotonics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China;
                [2 ]Department of Dermatology, Shanghai East Hospital, Shanghai, People’s Republic of China;
                [3 ]Department of Dermatology, Shanghai Changzheng Hospital, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Qiushi Ren, Institute for Laser Medicine and Biophotonics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China, Tel +86 021 342 040 78, Email qsren@ 123456sjtu.edu.cn
                Jianghan Chen, Department of Dermatology, Shanghai Changzheng Hospital, Shanghai 200003, People’s Republic of China, Tel/Fax +86 021 818 854 92, Email chenjinghan@ 123456126.com
                Article
                ijn-6-905
                10.2147/IJN.S17503
                3124396
                21720503
                1e2dce88-da5d-46ba-8746-9e6576296209
                © 2011 Xu et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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                Original Research

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