title: A novel performing PEG-cholane nanoformulation for Amphotericin B delivery.
abstract: 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 10(3) times the AmB solubility with a 12:1 AmB/PEG5 kDa-cholane molar ratio (2:1 w/w ratio). Dynamic light scattering and transmission electron microscopy analyses showed that PEG5 kDa-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.
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Italy; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid, Plaza Ramon y Cajal S/N, 28040 Madrid, Spain.
authors: Claudia
authors: C
authors: Luengo-Alonso
authors: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid, Plaza Ramon y Cajal S/N, 28040 Madrid, Spain.
authors: Juan José
authors: JJ
authors: Torrado
authors: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid, Plaza Ramon y Cajal S/N, 28040 Madrid, Spain.
authors: Maria Paloma
authors: MP
authors: Ballesteros
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Italy.
authors: Alessio
authors: A
authors: Malfanti
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Italy.
authors: Sara
authors: S
authors: Bersani
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Italy.
authors: Stefano
authors: S
authors: Salmaso
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Italy. Electronic address: paolo.caliceti@unipd.it.
authors: Paolo
authors: P
authors: Caliceti
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002793:Cholic Acids / Q000008:administration & dosage* / Q000737:chemistry*; D002942:Circular Dichroism; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D008823:Micelles; D008826:Microbial Sensitivity Tests; D036103:Nanotechnology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D002793:Cholic Acids; D008823:Micelles; D012709:Serum Albumin; D011092:Polyethylene Glycols; D000666:Amphotericin B; C028210:monomethoxypolyethylene glycol; C007036:cholanic acid
keywords: Amphotericin B; Cholanic acid; Micelles; PEG(5kDa)-cholane; Poly(ethylene glycol)