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

Abstract

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)), Xray 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.

Optimization of layering technique and secondary structure analysis during the formulation of nanoparticles containing lysozyme by quality by design approach

“…Most importantly, the technique is usually conducted under normal experimental conditions and mainly in an aqueous solution, hence it is suitable to encapsulate proteins and polypeptide drugs [ 24 ], and recently the application of three layers of polyelectrolyte polymers in anticancer NPs demonstrated cancer-cell targeting with efficient internalization [ 25 ]. In our previous work NPs containing human interferon-α were formulated with the LBL approach by applying chitosan and polystyrene sulphonate [ 26 ]. The aim of our present work is to formulate, analyse and optimize core-shell type NPs containing LYS, as well as to write mathematical relationships between process parameters and product parameters.…”

Forms and Methods for Interferon’s Encapsulation

“…Kristó et al (2020) developed a nanoparticle with a core/shell structure, whose core was composed of IFN-α associated with human serum albumin, and the shell was constituted by three consecutive layers of polystyrene-chitosan-polystyrene sulfonate-sulfonate, respectively. This system exhibited sustained release for ten days without reducing cytokine biological activity in a higher organism ( Pannon rabbits) [ 152 ].…”

Forms and Methods for Interferon's Encapsulation

“…In 2017, Cánepa et al synthesized chitosan nanoparticles that exhibited comparable antiviral activity to commercial IFNα in in vitro models.In the same study, preliminary in vivo assays in a CF1 mouse murine model showed that the molecule was detectable in the blood after one hour of oral administration of the formulation[109].Imperiale et al complemented this study in 2019 by demonstrating that the system provided bioavailability comparable to intravenously administered IFNα-2b in murine BALB/c mouse models[110].Kristó et al (2020) developed a nanoparticle with a core/shell structure, whose core was composed of IFNα associated with human serum albumin, and the shell was constituted by three consecutive layers of polystyrene-chitosanpolystyrene sulfonate-sulfonate, respectively. This system exhibited sustained release for ten days without reducing cytokine biological activity in a higher organism (Pannon rabbits)[111].IFNßFodor-Kardos et al in 2020 reported the first IFNß nanoencapsulation procedure. This research obtained nanometric particles with high encapsulation efficiency (>95%) to treat multiple sclerosis.…”