A novel pH-sensitive interferon-¦Â (INF-¦Â) oral delivery system for application in multiple sclerosis
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- 作者：Pierre P.D. Kondiah ; Lomas K. Tomar ; Charu Tyagi ; Yahya E. Choonara ; Girish Modi ; Lisa C. du Toit ; Pradeep Kumar ; Viness Pillay
- 关键词：Oral delivery system ; Interferon-¦Â (INF-¦Â) ; Insulin ; Box&ndash ; Behnken experimental design ; Copolymeric microparticulate system ; pH-responsive
- 刊名：International Journal of Pharmaceutics
- 出版年：2013
- 出版时间：18 November, 2013
- 年：2013
- 卷：456
- 期：2
- 页码：459-472
- 全文大小：3237 K
文摘
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-¦Â (INF-¦Â). 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-¦Â. 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-¦Â loading efficiency of 53.25 % . The in vitro release of INF-¦Â 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-¦Â in the New Zealand White rabbit, and compared to a known subcutaneous formulation. The system showed an astounding effective release profile over 24 h with higher INF-¦Â plasma concentrations compared with the subcutaneous injection formulation.