TNF-α blocker effect of naringenin-loaded sericin microparticles that are potentially useful in the treatment of psoriasis.

Theodora Chlapanidas,Daniela Rossi,Silvio Faragò,Sara Perteghella,Flavio Leoni,Raffaella Gaggeri,Emanuela Martino,Simona Collina,Mario Marazzi

doi:10.3390/ijms150813624

Abstract

This study aims to evaluate the effect of combined use of the racemic flavanone Naringenin (NRG) and the protein sericin as TNF-α blockers. Sericin (SMs) and (R/S) NRG-loaded Sericin (SNRGMs) microparticles were prepared by spray-drying, characterized in terms of morphology and particle size distribution, and encapsulation efficiency was determined. Concerning morphology and particle size distribution of microparticles, results indicated that they were not affected by the presence of NRG. The encapsulation efficiency was almost quantitative (93%), thus proving that sericin can be advantageously loaded with (R/S) NRG. Biological evaluation of (R/S) NRG, SMs and SNRGMs was then performed in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (hPBMC). SNRGMs resulted cytotoxic at the higher dose used (200 μg/mL) and the effect was greater than (R/S) NRG alone. Moreover, even if sericin alone was not effective in suppressing LPS-induced serum TNF-α levels, SNRGMs loaded with 9.3% of (R/S) NRG were significantly more potent than (R/S) NRG alone. In summary, this study provides the proof of concept that sericin-based microspheres loaded with TNF-α-blockers could contribute to the down regulation of the cytokine and represents the starting point for the development of new topical formulations for the treatment of middle-stage psoriasis.

Highlights

Our ethnobotanical-directed search for novel anti-inflammatory drugs revealed that Amygdalus lycioidesSpach, an Iranian medicinal plant, holds interesting anti-inflammatory activity exerted via a TNF-α-blocker mechanism [1,2]
The results indicated that (i) sericin microspheres (SMs) did not have cytotoxic effect on human peripheral blood mononuclear cells (hPBMC) stimulated by LPS; (ii) (R/S) NRG significantly inhibited cell viability only at the higher dose (200 μg/mL); and (iii) SNRGMs are cytotoxic at the higher dose used
Overall results presented indicate that sericin microparticles loaded with naringenin are more potent than (R/S) NRG alone in inhibiting the TNF-α production on LPS-stimulated human PBMC and, that this effect is not due to an unspecific cytotoxic activity

Summary

Introduction

Our ethnobotanical-directed search for novel anti-inflammatory drugs revealed that Amygdalus lycioidesSpach, an Iranian medicinal plant, holds interesting anti-inflammatory activity exerted via a TNF-α-blocker mechanism [1,2]. We studied the anti-inflammatory properties of silk sericin. Sericin was shown to inhibit cell proliferation of human peripheral blood mononuclear cells (hPBMC) stimulated by the mitogen phytohaemagglutinin (PHA) [5]. These results suggested that we evaluate the effect of the combined use of (R/S) NRG and sericin as TNF-α blockers. We addressed our efforts towards the loading of (R/S) NRG into sericin microparticles, followed by the evaluation of their inhibitory effect in a cellular model of TNF-α production (i.e., lipopolysaccharide (LPS)-stimulated hPBMC). Recent genetic and immunological advances have greatly increased understanding of the pathogenesis of this disease as an immune-mediated inflammatory disorder [6], in which the cytokine TNF-α plays a crucial role [7,8]

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