title: A novel pH-sensitive interferon-β (INF-β) oral delivery system for application in multiple sclerosis.
abstract: pH-sensitive microparticles were prepared using trimethyl-chitosan (TMC), poly(ethylene glycol)dimethacrylate (PEGDMA) and methacrylic acid (MAA) by free radical suspension polymerization, for the oral delivery of interferon-β (INF-β). The microparticles were subsequently compressed into a suitable oral tablet formulation. A Box-Behnken experimental design was employed for generating a series of formulations with varying concentrations of TMC (0.05-0.5 g/100 mL) and percentage crosslinker (polyethylene glycol diacrylate) (3-8%, w/w of monomers), for establishment of an optimized TMC-PEGDMA-MAA copolymeric microparticles. For pragmatism, insulin was initially employed as the model peptide for undertaking the preliminary experimentation and the optimized formulation was subsequently evaluated using INF-β. The prepared copolymeric microparticulate system was characterized for its morphological, porositometric and mucoadhesive properties. The optimized microparticles with 0.5 g/100 mL TMC and 3% crosslinker had an INF-β loading efficiency of 53.25%. The in vitro release of INF-β was recorded at 74% and 3% in intestinal (pH 6.8) and gastric (pH 1.2) pH from the oral tablet formulation, respectively. The tablet was further evaluated for plasma concentration of INF-β in the New Zealand White rabbit, and compared to a known subcutaneous formulation. The system showed an astounding effective release profile over 24h with higher INF-β plasma concentrations compared with the subcutaneous injection formulation.
authors.affiliation: University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, 7 York Road, Parktown, Johannesburg 2193, South Africa.
authors.forename: Pierre P D
authors.initials: PP
authors.lastname: Kondiah
authors.forename: Lomas K
authors.initials: LK
authors.lastname: Tomar
authors.forename: Charu
authors.initials: C
authors.lastname: Tyagi
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016899:Interferon-beta / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D010316:Particle Size; D011817:Rabbits
chemical_list: D016899:Interferon-beta
keywords: Box–Behnken experimental design; Copolymeric microparticulate system; Insulin; Interferon-β (INF-β); Oral delivery system; pH-responsive