Insulin-loaded polymeric mucoadhesive nanoparticles: development, characterization and cytotoxicity evaluation

Tiago Henrique Honorato Gatti,Isabel Cristine Da Silva,Marlus Chorilli,Fernando Rogério Pavan,Maria Palmira Daflon Gremião,Leonardo Miziara Barboza Ferreira,Josimar Oliveira Eloy

doi:10.1590/s2175-97902018000117314

Tiago Henrique Honorato Gatti, Isabel Cristine Da Silva + Show 5 more

Open Access

https://doi.org/10.1590/s2175-97902018000117314

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Abstract

Mucoadhesive nanoparticles are particularly interesting for delivery through nasal or pulmonary routes, as an approach to overcome the mucociliary clearance. Moreover, these nanoparticles are attractive for peptide and protein delivery, particularly for insulin to treat diabetes, as an alternative to conventional parenteral administration. Thus, chitosan, a cationic mucoadhesive polysaccharide found in shells of crustaceans, and the negatively-charged dextran sulfate are able to form nanoparticles through ionic condensation, representing a potential insulin carrier. Herein, chitosan/dextran sulfate nanoparticles at various ratios were prepared for insulin loading. Formulations were characterized for particle size, zeta potential, encapsulation efficiency, scanning electron microscopy, differential scanning calorimetry, and in vitro drug release. Moreover, the interaction with mucin and the cytotoxicity against a lung cell line were studied, which altogether have not been addressed before. Results evidenced that a proper selection of polyelectrolytes is necessary for smaller particle size formation and also the composition and zeta potential impact encapsulation efficiency, which is benefited by the positive charge of chitosan. Insulin remained stable after encapsulation as evidenced by calorimetric assays, and was released in a sustained manner in the first 10 h. Positively-charged nanoparticles based on chitosan/dextran-sulfate at the ratio of 6:4 successfully interacted with mucin, which is a prerequisite for delivery to mucus-containing tissues. Finally, insulin-loaded nanoparticles displayed no cytotoxicity effect against lung cells at tested concentrations, suggesting the potential for further in vivo studies.

Highlights

Diabetes mellitus represents the most prevalent metabolic disorder nowadays, with 345 million people affected worldwide (Sah et al, 2016)
The ionic coacervation is environment friendly and the results obtained over the years with nanoparticles based on chitosan and dextran sulfate underline the high potential of this strategy for development of human medicine (Delair, 2011)
We reported the development and characterization of nanoparticles based on chitosan/ dextran sulfate formed by polyelectrolytes condensation for insulin loading

Summary

Introduction

Diabetes mellitus represents the most prevalent metabolic disorder nowadays, with 345 million people affected worldwide (Sah et al, 2016). It is believed that in 2030 the number of patients will raise up to 552 million, which can be considered a threat for public health (Whiting et al, 2011). A major concern is that life expectancy is reduced by many years in patients with type 1 or 2 diabetes. For Type 1 diabetes patients, due to insufficient insulin production, exogenous hormone is needed (Salvioni et al, 2016). The peptide insulin is the most effective drug for diabetes treatment, with high specificity and activity (Fonte et al, 2014). The subcutaneous injection, which must pass through the skin for systemic effect, results in considerable tissue trauma and pain (Sintov, Levy, Botner 2010; Li et al, 2017)

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