Mesoporous particle-based microcontainers for intranasal delivery of imidazopyridine drugs

Abstract

The aim of this study was to develop mesoporous containers for entrapment of imidazopyridines, such as sedative–hypnotic medicine zolpidem, anxiolytic agent alpidem and their derivatives. For this purpose, calcium carbonate (size 1.2 µm (PDI: 0.6), zeta potential: −10 mV), manganese carbonate (2.5 µm (PDI: 0.5), zeta potential: −12 mV) and titanium dioxide particles (3.7 µm (PDI: 0.4), zeta potential: −15 mV) were used. The compounds were encapsulated applying two techniques: adsorption on the preformed particles and co-precipitation during the synthesis of the particles. The polymer shell of the containers was formed by electrostatic adsorption of polyelectrolytes on the surface of the particles. The best encapsulation efficacy was shown for zolpidem incorporated into calcium carbonate (5.4%) and manganese carbonate (4.6%) by adsorption. Release of the compounds from the containers based on the proposed particles were characterised by the short time burst effect (<10 min) followed by desorption prolongation by formation of polymer shell. X-ray microtomography results demonstrate the prolonged retention of the containers with the mucoadhesive shell in the nasal cavity.

Keywords:

• Mesoporous particles
• microcontainers
• drug delivery
• imidazopyridines
• intranasal delivery

Acknowledgements

This work was performed using the equipment of the Shared Research Center FSRC ‘Crystallography and Photonics’ RAS. We gratefully acknowledge Vladimir Artemov for obtaining scanning microscopy images of the samples.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation within the State assignment FSRC ‘Crystallography and Photonics’ RAS in part of the synthesis and characterisation of the mesoporous particles and by National Research Center ‘Kurchatov Institute’ and the Russian Foundation for Basic Research and Moscow city Government (research project No. 15-33-70032 ‘mol_a_mos’) in part of the container fabrication and their investigation