Transmucosal Solid Lipid Nanoparticles to Improve Genistein Absorption via Intestinal Lymphatic Transport.

Antonella Obinu,Giovanni Pietro Burrai,Elisabetta Gavini,Rossana Migheli,Grazia Galleri,Elisabetta Antuofermo,Paolo Giunchedi,Roberta Cavalli,Giovanna Rassu

doi:10.3390/pharmaceutics13020267

Antonella Obinu, Giovanni Pietro Burrai + Show 7 more

Open Access

https://doi.org/10.3390/pharmaceutics13020267

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Journal: Pharmaceutics	Publication Date: Feb 16, 2021
Citations: 24	License type: CC BY 4.0

Affiliation: University of Sassari, University of Turin

Abstract

Genistein (GEN) is a soy-derived isoflavone that exhibits several biological effects, such as neuroprotective activity and the prevention of several types of cancer and cardiovascular disease. However, due to its poor water solubility and the extensive first-pass metabolism, the oral bioavailability of GEN is limited. In this work, solid lipid nanoparticles (SLN) were developed to preferentially reach the intestinal lymphatic vessels, avoiding the first-pass metabolism of GEN. GEN-loaded SLN were obtained by a hot homogenization process, and the formulation parameters were chosen based on already formulated studies. The nanoparticles were characterized, and the preliminary in vitro chylomicron formation was evaluated. The cell uptake of selected nanocarriers was studied on the Caco-2 cell line and intestinal mucosa. The SLN, characterized by a spherical shape, showed an average diameter (about 280 nm) suitable for an intestinal lymphatic uptake, good stability during the testing time, and high drug loading capacity. Furthermore, the intestinal mucosa and Caco-2 cells were found to uptake SLN. The approximately two-fold increase in particle size suggested a possible interaction between SLN and the lipid components of chylomicrons like phospholipid; therefore, the results may support the potential for these SLN to improve oral GEN bioavailability via intestinal lymphatic absorption.

Highlights

The lymphatic system is part of the circulatory system, playing a significant role in the immune system and in the maintenance of the liquid balance in the body: it collects excess fluid and plasma proteins from the interstitial fluid and deposits them in the bloodstream.lymphatic vessels represent a primary method of dissemination for infectious agents and metastatic tumor cells all throughout the body [1,2]
Based on the preliminary results reported in the supplementary files, the suitable technological parameters for the preparation of Solid lipid nanoparticles (SLN) proper to be loaded with GEN were identified; the sample B-SLNc (Table 1 of Supplementary Material) was selected as an unloaded leader formulation for the GEN loading process
The best emulsifier concentration was found to be 0.5% (w/v) because B-SLN presented the best results for intestinal lymphatic transport, in terms of particle size (20–500 nm) [3]

Summary

Introduction

Lymphatic vessels represent a primary method of dissemination for infectious agents and metastatic tumor cells all throughout the body [1,2]. The gastrointestinal tract is rich in lymphatic and blood vessels, representing an interesting opportunity for the site-specific absorption of lipid drugs, proteins, vaccines, and peptides following oral administration [4]. Solid lipid nanoparticles (SLN) are suitable carriers to deliver drugs to specific intestinal associated structures, such as lymph nodes and lymphatic vessels [5]. They show features that make them suitable candidates for intestinal lymphatic drug transport

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