title: Use of hydrophobins in formulation of water insoluble drugs for oral administration.
abstract: The poor water solubility of many drugs requires a specific formulation to achieve a sufficient bioavailability after oral administration. Suspensions of small drug particles can be used to improve the bioavailability. We here show that the fungal hydrophobin SC3 can be used to make suspensions of water insoluble drugs. Bioavailability of two of these drugs, nifedipine and cyclosporine A (CyA), was tested when administered as a SC3-based suspension. SC3 (in a 1:2 (w/w) drug:SC3 ratio) or 100% PEG400 increased the bioavailability of nifedipine to a similar degree (6+/-2- and 4+/-3-fold, respectively) compared to nifedipine powder without additives. Moreover, SC3 (in a 7:1 (w/w) drug:hydrophobin ratio) was as effective as a 20-fold diluted Neoral formulation by increasing bioavailability of CyA 2.3+/-0.3-fold compared to CyA in water. Interestingly, using SC3 in the CyA formulation resulted in a slower uptake (p<0.001 in T(max)) of the drug, with a lower peak concentration (C(max) 1.8 mg ml(-1)) at a later time point (T(max) 9+/-2 h) compared to Neoral (C(max) 2.2 mg ml(-1); T(max) 3.2+/-0.2). Consequently, SC3 will result in a more constant, longer lasting drug level in the body. Taken together, hydrophobins are attractive candidates to formulate hydrophobic drugs.
authors.affiliation: BioMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Haas Jimoh Akanbi
authors.forename: Eduard
authors.initials: E
authors.lastname: Post
authors.forename: Anita
authors.initials: A
authors.lastname: Meter-Arkema
authors.forename: Rick
authors.initials: R
authors.lastname: Rink
authors.forename: George T
authors.initials: GT
authors.lastname: Robillard
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
authors.forename: Han A B
authors.initials: HA
authors.lastname: Wösten
authors.forename: Karin
authors.initials: K
authors.lastname: Scholtmeijer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016572:Cyclosporine / Q000097:blood; D004339:Drug Compounding; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012996:Solutions; D014867:Water / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D012996:Solutions; D014867:Water; D016572:Cyclosporine; D009543:Nifedipine