Preparation and investigation of core-shell nanoparticles containing human interferon-α.

Sustained release of active interferon-α (IFN-α) has been achieved from core-shell nanoparticles (NPs) prepared by aqueous precipitation of IFN-α-enriched human serum albumin (HSA-IFN-α) and layer-by-layer (L-b-L) by coating of the IFN-α NPs with poly(sodium-4-styrene) sulphonate (PSS) and chitosan (Chit). The concentration and the pH of HSA solution were optimized during the development of this method. Dynamic light scattering (DLS), zeta-potential, thermal analysis (differential scanning calorimetry (DSC) and termogravimetry (TG)), X-ray diffraction (XRD), IFN-α activity and morphology (transmission electron microscope (TEM)) studies were used to control the preparation and analyse the products. The dissolution kinetics of NPs was measured in vitro over 7 days in Hanson dissolution tester with Millex membrane. In vivo studies in Pannon white rabbit detected steady IFN-α plasma level for 10 days after subcutaneous injection administration of the HSA-IFN-α NPs. The IFN-α plasma concentration was detected by using the enzyme-linked immunosorbent assay (ELISA) method. In the present paper we discuss the preparation method, the optimization steps and the results of in vitro and in vivo release studies. It was established that 76.13% HSA-IFN-α are encapsulated in the core-shell NPs.

Study of the effects of drugs on the structures of sucrose esters and the effects of solid-state interactions on drug release.

Sucrose esters (SEs) have a wide range of hydrophilic-lipophilic balance (HLB) values (1-16), and hence can be applied as surfactants, or as solubility or penetration enhancers. In general, SEs are used in hot-melt technology, because of their low melting points, but literature data are not available on the effects of active agents on the structures of SEs and the possible solid-state interactions. In this study, drug-SE products were prepared by melt technology and investigated by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), rheological measurements and dissolution tests. The model drugs meloxicam and diclofenac sodium and three SEs with different polarities (P1670, S970 and B370) were chosen for the preparation of the products. The DSC and XRPD results revealed that the structures of the SEs were rearranged, with a decrease in the degree of crystallinity. The dissolved drug molecules broke down the structures of the SEs, but were not built into the crystalline phase of the carrier. The dissolution of the drugs was influenced by the different HLB values and gel-forming behaviour of the SEs, and also by the polarity of the drug and the interactions between the drug and the SEs.