How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models

Abstract

Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats’ glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.

Synthesis and In Vivo Evaluation of Insulin-Loaded Whey Beads as an Oral Peptide Delivery System

“…The secondary structure of native insulin in SIF showed characteristic troughs at 211 nm and 222 nm [ 41 ]. Bead-released insulin demonstrated a profile similar to native insulin with little differences between three independent batches ( Figure 3 ).…”

Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

“…First, NPs could act as a physical barrier to the cells. This occlusive effect of NPs has been investigated by several groups; nevertheless, a very similar formulation made (with the same core) by our group showed that NPs were safe for the tested cells [ 43 ]. Thus, it should be another reason: all samples were tested in a Pluronic F-127 (POLX) gel to better mimic the potential use of insulin-loaded NPs in the further studies: topical use.…”

Enhancement of oral bioavailability of natural compounds and probiotics by mucoadhesive tailored biopolymer-based nanoparticles: A review

“…Isothermal titration calorimetry and atomic force microscopy have also been applied to verify the interaction of NPs with a mucin solution (Cheng et al, 2018). More recently, static lattice atomistic simulation has been proposed for in silico mucin adhesion evaluation in terms of molecular, energy and geometrical attributes (Amaral et al, 2020).…”