Development and Characterization of Chitosan Microparticles-in-Films for Buccal Delivery of Bioactive Peptides

Abstract

Nowadays, bioactive peptides are used for therapeutic applications and the selection of a carrier to deliver them is very important to increase the efficiency, absorption, release, bioavailability and consumer acceptance. The aim of this study was to develop and characterize chitosan-based films loaded with chitosan microparticles containing a bioactive peptide (sequence: KGYGGVSLPEW) with antihypertensive properties. Films were prepared by the solvent casting method, while the microparticles were prepared by ionic gelation. The final optimized chitosan microparticles exhibited a mean diameter of 2.5 µm, a polydispersity index of 0.46, a zeta potential of +61 mV and a peptide association efficiency of 76%. Chitosan films were optimized achieving the final formulation of 0.79% (w/v) of chitosan, 6.74% (w/v) of sorbitol and 0.82% (w/v) of citric acid. These thin (±0.100 mm) and transparent films demonstrated good performance in terms of mechanical and biological properties. The oral films developed were flexible, elastic, easy to handle and exhibited rapid disintegration (30 s) and an erosion behavior of 20% when they came into contact with saliva solution. The cell viability (75–99%) was proved by methylthiazolydiphenyl-tetrazolium bromide (MTT) assay with TR146 cells. The chitosan mucoadhesive films loaded with peptide–chitosan microparticles resulted in an innovative approach to perform administration across the buccal mucosa, because these films present a larger surface area, leading to the rapid disintegration and release of the antihypertensive peptide under controlled conditions in the buccal cavity, thus promoting bioavailability.

Biocompatible Inhibitor Based on Chitosan and Amphiphilic Peptide against Mutant Huntingtin Toxicity

“…Chitosan is a linear copolymer consisting of glucosamine and N ‐acetylglucosamine that exhibits a high degree of N ‐deacetylation. Chitosan‐decorated nanomaterials have currently been applied to the delivery of peptides, proteins, small molecules, genes, and multitheranostics drugs for satisfactory biodegradability, biocompatibility, and non‐immunogenicity in chitosan . Earlier studies also reported that chitosan and its derivative could inhibit the fibrillogenesis of amyloid β‐protein Aβ‐40 and/or age‐related diseases .…”

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…However, low solubility under physiological pH possesses some limitations. Due to its mucoadhesive nature [101], CS has been used as a vehicle to deliver drugs to nasal [102], ocular [103], buccal [104], and pulmonary tissues [105]. For drug delivery purposes, CS is used in the form of nano/microparticles which is synthesized by emulsion, coacervation/precipitation, ionic gelation, reverse micellar methods, etc.…”

Development and Characterization of Inkjet Printed Edible Films for Buccal Delivery of B-Complex Vitamins

“…The buccal delivery of APIs is an alternative, non-invasive route of administration that provides beneficial health effects. The buccal mucosa is a highly vascularized administration site, providing the high permeability for many APIs and the avoidance of the first pass effect [20]. Buccal formulations are recommended for pediatric dosage forms as they are patient-friendly and adjustable to the different physiological and pharmacokinetic profiles of infants, children and adolescents [21].…”