OBJECTIVE: Formulation of methacrylic acid-methyl methacrylate copolymer-coated capsules filled with chitosan nanoparticles loaded with rHuKGF for oral delivery.
METHODS: We report on chitosan nanoparticles (CNPs) with diameter < 200 nm, prepared by ionic gelation, loaded with rHuKGF and filled in methacrylic acid-methyl methacrylate copolymercoated capsules for oral delivery. The pharmacokinetic parameters were determined based on the serum levels of rHuKGF, following a single intravenous (IV) or oral dosages using a rabbit model. Furthermore, fluorescent microscope imaging was conducted to investigate the cellular uptake of the rhodamine-labelled rHuKGF-loaded nanoparticles. The proliferation effect of the formulation on FHs 74 Int cells was studied as well by MTT assay.
RESULTS: The mucoadhesive and absorption enhancement properties of chitosan and the protective effect of methacrylic acid-methyl methacrylate copolymer against rHuKGF release at the stomach, low pH, were combined to promote and ensure rHuKGF intestinal delivery and increase serum levels of rHuKGF. In addition, in-vitro studies revealed the protein bioactivity since rHuKGFloaded CNPs significantly increased the proliferation of FHs 74 Int cells.
CONCLUSION: The study revealed that oral administration of rHuKGF-loaded CNPs in methacrylic acid-methyl methacrylate copolymer-coated capsules is practically alternative to the IV administration since the absolute bioavailability of the orally administered rHuKGF-loaded CNPs, using the rabbit as animal model, was 69%. Fluorescent microscope imaging revealed that rhodaminelabelled rHuKGF-loaded CNPs were taken up by FHs 74 Int cells, after 6 hours' incubation time, followed by increase in the proliferation rate.