Evaluation of polyelectrolyte and emulsion covalent crosslink of chitosan for producing mesalasine loaded submicron particles

Edeilson Vitor Gonzaga,Gabriel José Silveira Lacerda,Liliane Neves Pedreiro,Flávia Chiva Carvalho,Valéria De Moura Leite Naves,Gislaine Ribeiro Pereira,Beatriz Lemos Piantino,Maria Palmira Daflon Gremião

doi:10.1590/s2175-97902019000217847

Abstract

This study evaluates various techniques for producing mesalamine (5ASA)-loaded particles employing chitosan as a biopolymer: (1) the polyelectrolyte complexation of chitosan with phthalate hypromelose (HP), (2) the chemical crosslinking of chitosan with genipin and (3) the water-in-oil emulsion method associated with chemical crosslinking with genipin. Systems were characterized by dynamic light scattering, zeta potential (ζ), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and a drug release profile. Method (1) was efficiently produced unloaded nanoparticles (491 nm, PdI=0.26 and ζ = 23.2), but the conditions for chitosan and HP cross-linking enhanced the precipitation of 5ASA. Method (2) caused the degradation of the drug. Method 3 produced sub-micron and microparticles, thereby varying the agitation method; 3 h magnetic agitation resulted in 2692 nm, Pdi = 0.6 and ζ = 46, while Ultra-Turrax, 5 min produced submicron particles (537 nm, PdI = 0.6). The percentage yield was approximately 50%, which is very satisfactory considering the impossibility of encapsulating 5ASA using other methods. FTIR showed the covalent interaction of chitosan and genipin. The drug release was rapid in acidic fluid, but in neutral pH a slower release was obtained in the initial stage, followed by rapid release, which may ensure the controlled release of 5ASA in the colon.

Highlights

Inflammatory bowel disease (IBD) is a generalized term for a group of chronic diseases affecting the gastrointestinal system, including ulcerative colitis (UC) and Crohn’s disease (CD) (Hua et al, 2015)
The main obstacle faced by treatment with 5-aminosalicylic acid (5ASA) in conventional dosage forms is to achieve local levels of the drug in the inflamed mucosa without the use of dosage forms that are less acceptable to patients, such as enemas
Method of polyelectrolyte complexation of chitosan Nanoparticles were produced by low-viscosity chitosan dispersion at 0.1% w/v in 1% acetic acid, pH=5.5 and hypromellose phthalate (HP) as ionic cross-linker at 0.5% w/v in NaOH 1 M, and 5ASA at 5 mg/mL in HCl 1 M pH=5.5 was incorporated into the chitosan dispersion to have the drug at 5% w/w to the polymeric weigh

Summary

Introduction

Inflammatory bowel disease (IBD) is a generalized term for a group of chronic diseases affecting the gastrointestinal system, including ulcerative colitis (UC) and Crohn’s disease (CD) (Hua et al, 2015). Method of polyelectrolyte complexation of chitosan Nanoparticles were produced by low-viscosity chitosan dispersion at 0.1% w/v in 1% acetic acid, pH=5.5 and hypromellose phthalate (HP) as ionic cross-linker at 0.5% w/v in NaOH 1 M (pH=5.5), and 5ASA at 5 mg/mL in HCl 1 M pH=5.5 was incorporated into the chitosan dispersion to have the drug at 5% w/w to the polymeric weigh.

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Conclusion