A novel performing PEG-cholane nanoformulation for Amphotericin B delivery

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• 作者：Claudia Luengo-Alonso^a ; ^b ; Juan José ; Torrado^b ; Maria Paloma Ballesteros^b ; Alessio Malfanti^a ; Sara Bersani^a ; Stefano Salmaso^a ; Paolo Caliceti^a ; ^{paolo.caliceti@unipd.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Amphotericin B ; Poly(ethylene glycol) ; PEG5kDa-cholane ; Micelles ; Cholanic acid
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：10 November 2015
• 年：2015
• 卷：495
• 期：1
• 页码：41-51
• 全文大小：1455 K

文摘

A novel formulation for amphotericin B (AmB) delivery has been developed using micelle-forming 5 kDa monomethoxy-polyethylene glycol functionalized with cholanic acid (PEG_5kDa-cholane). This polymer was found to increase 10³ times the AmB solubility with a 12:1 AmB/PEG_5kDa-cholane molar ratio (2:1 w/w ratio). Dynamic light scattering and transmission electron microscopy analyses showed that PEG_5kDa-cholane associated with AmB to form 30 nm micelles. Isothermal titration calorimetry analyses performed at different pH showed that PEG_5kDa-cholane interacts with AmB according to multiple-site association profiles. Affinity constants and enthalpy and entropy changes were found to depend on pH, suggesting that the polymer interaction depends on the AmB ionization and aggregation. The freeze-dried product could be promptly re-dispersed forming a colloidal dispersion with the biopharmaceutical features of the freshly prepared micelles, namely AmB solubility and micelle size. The dispersion was stable over one month incubation at room temperature. FT-infrared spectrometry, differential scanning calorimetry and X-ray diffractometry showed that in the freeze-dried product, AmB intimately interacts with PEG_5kDa-cholane. In presence of serum albumin, AmB formulated with PEG_5kDa-cholane was found to undergo less extensive and slower disaggregation than in Fungizone^®. Antifungal activity studies performed using Candida albicans showed that AmB/PEG_5kDa-cholane was 15% more active than AmB in buffer.