Preparation Of Microencapsulated Interferon For Oral Administration And Evaluation Of Its Properties

Interferon (IFN), a kind of cytokines, exhibits various biological Activities including antiviral, antiproliferation and immunoloregulation, etc. Currently main clinical formulations of interferon are injectable powder, injectable water and sprays for external use, etc. But these traditional forms exist many problems,such as poor stability, strong side effect, short half-life in vivo, low bioavailability. In recent years, with the development of macromolecular materia and pharmacy, people gradually developed some slow-release formulation of protein and peptide drugs which can improve the bioavailability of drugs by reducing the loss of drugs in the gastrointestinal tract and releasing drugs at the absorption site in the colon. Among the developed technologies, microspheres have the potential to be the most promising carrier to realize oral administration of protein and peptide drugs. Although materials and techniques to prepare microspheres have been extensively studied, microspheres as carrier for protein delivery still has technical problems, such as toxicity and side-effect of materials, high cost, severe condition for production, large diameter and low encapsulation efficiency. In order to solve the problems above, studies on microspheres for oral administration of proteins and peptide drugs were carried out in this report, using interferon as the model durg and the biocompatible natural materials alglnate and chitosan as the carrier material.In this study, one-step method was carried out to prepare the interferon microcapsules, by dropping the alginate solution of interferon to the chitosan solution of CaCl2. Then the four factors(concentration of sodium alginate, IFN dosage, chitosan concentration, calcium chloride concentrations) which had the larger effect on the microcapsules preparation were optimized. Then combined encapsulation efficiency (EE) and microspheres strength (MS) and established comprehensive evaluation index (EI) to evaluate the process prescriptions. As a result, the optimal results were obtained under the following conditions:chitosan concentration0.4%, sodium alginate2.0%, calcium chloride1.0%, interferon0.3%, and encapsulation efficiency and mechanical strength of these microcapsules were up to96.02%,97%.Other valid parameters, such as the microcapsule morphology, particle size and these distribution, drug loading, and drug release were also evaluated. As a result, under the optimized condition, the interferon microcapsules with mean diameter about12μm, drug loading about14.01mg/g and Accumulative releasing about90%in the SIF.Finally, in the WISH/VSV system, the interferon retentive activity of interferon microcapsules was about87%. So the preparation process of the microcapsules was less effect on interferon interferon activity. Consequently, it can be said that the chitosan-alginate microcapsules can be offerd for the temporary protection of interferon against acidic during gastric passage. Thus the method provides a reference for the preparation of the oral administration dosage forms of other protein peptide drugs.