A novel pH-sensitive interferon-β (INF-β) oral delivery system for application in multiple sclerosis

• Published in: International journal of pharmaceutics 2013-11, Vol.456 (2), p.459-472
• Main Authors: Kondiah, Pierre P.D., Tomar, Lomas K., Tyagi, Charu, Choonara, Yahya E., Modi, Girish, du Toit, Lisa C., Kumar, Pradeep, Pillay, Viness
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Box–Behnken experimental design; Chemistry, Pharmaceutical; Copolymeric microparticulate system; Drug Delivery Systems - methods; Humans; Hydrogen-Ion Concentration; Insulin; Interferon-beta - administration & dosage; Interferon-beta - blood; Interferon-beta - chemistry; Interferon-β (INF-β); Multiple Sclerosis - blood; Multiple Sclerosis - drug therapy; Multiple Sclerosis - metabolism; Oral delivery system; Particle Size; pH-responsive; Rabbits
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.08.038

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 (0.05–0.5g/100mL) 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 0.5g/100mL 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.