Formulation and In-Vitro Evaluation of Enteric Coated Capsules Filled with Recombinant Human Keratinocyte Growth Factor Loaded Chitosan Nanoparticles

Recombinant human keratinocyte growth factor (rHuKGF) is a protein used to treat oral mucositis, small intestinal ulceration and colitis in hematological malignancies patients who are receiving radio and chemotherapy.... [ view full abstract ]

Recombinant human keratinocyte growth factor (rHuKGF) is a protein used to treat oral mucositis, small intestinal ulceration and colitis in hematological malignancies patients who are receiving radio and chemotherapy. Mucoadhesive chitosan nanoparticles are used to develop oral delivery systems. In this project, rHuKGF loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions with the presence and absence of PEG 2000 as a cryo-protectant. Size distribution and zeta potential of rHuKGF loaded chitosan nanoparticles were determined by using zeta-sizer. In addition, the morphology was determined by using field emission scanning electron microscope. Enzyme linked immunosorbent assay was used to determine the amount of rHuKGF that was loaded in chitosan nanoparticles. The prepared chitosan nanoparticles were filled in capsules and coated by enteric coating polymer kollicoat MAE 100 P, in-vitro dissolution studies were performed to evaluate the release of rHuKGF in a buffer solution having pH of the small intestine by using USP dissolution apparatus I. The rHuKGF loaded chitosan nanoparticles with and without PEG 2000 had spherical shape and positive surface charge. Particle size distribution of rHuKGF loaded chitosan nanoparticles was ranged from 119 to 385.7 nm. The rHuKGF loaded chitosan nanoparticles prepared with PEG 2000 capable to re-disperse fast without forming aggregates in simulated intestinal fluid pH 5.5 phosphate buffer solution. In-vitro release study showed the ability of kolicoat MAE 100 P to prevent the release of rHuKGF in simulated gastric fluid pH 1.2 and allow it to release in simulated phosphate buffer solutions pH higher than 5.5.