Formulation of Chitosan Microparticles for Enhanced Intranasal Macromolecular Compound Delivery: Factors That Influence Particle Size during Ionic Gelation

Abstract

Therapeutic macromolecules (e.g., protein and peptide drugs) present bioavailability challenges via extravascular administration. The nasal route presents an alternative non-invasive route for these drugs, although low bioavailability remains challenging. Co-administration of permeation enhancers is a promising formulation approach to improve the delivery of poorly bioavailable drugs. The aim of this study was to prepare and characterize chitosan microparticulate formulations containing a macromolecular model compound (fluorescein isothiocyanate dextran 4400, FD-4) and a bioenhancer (piperine). Ionic gelation was used to produce chitosan microparticle delivery systems with two distinct microparticle sizes, differing one order of magnitude in size (±20 µm and ±200 µm). These two microparticle delivery systems were formulated into thermosensitive gels and their drug delivery performance was evaluated across ovine nasal epithelial tissues. Dissolution studies revealed a biphasic release pattern. Rheometry results demonstrated a sol-to-gel transition of the thermosensitive gel formulation at a temperature of 34 °C. The microparticles incorporating piperine showed a 1.2-fold increase in FD-4 delivery across the excised ovine nasal epithelial tissues as compared to microparticles without piperine. This study therefore contributed to advancements in ionic gelation methods for the formulation of particulate systems to enhance macromolecular nasal drug delivery.

Piperine: A possible permeation enhancer for oral protein delivery

“…Chitosan microparticles were formulated to deliver the macromolecular compound fluorescein isothiocyanate dextran 4,400 with piperine as a bioenhancer by intranasal route. Microparticles with piperine showed a 1.2-fold increase in macromolecular delivery across nasal epithelia compared to microparticles without piperine [54]. This approach can be a promising alternative for noninvasive macromolecular delivery across nasal epithelia.…”

Impacts of chitosan and its nanoformulations on the metabolic syndromes: a review

“…These carriers represent a new paradigm in medication delivery because of their ability to treat neurodegenerative illnesses. Nasal drug delivery (NDD) is a non-invasive technique that shows great promise for efficiently administering a wide range of pharmaceuticals, including high molecular peptide and protein therapies and low molecular polar chemicals (Weyers et al, 2022). Therefore, the nasal mucosa serves as the main portal through which various therapeutic drugs are directed to specific disease-causing locations that enter the body (Kurono, 2022).…”