A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis, encapsulation and intranasal administration to mice

A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis, encapsulation and intranasal administration to mice Full article

Journal

Journal of Pharmacy and Pharmacology
ISSN: 0022-3573 , E-ISSN: 2042-7158

Output data

Year: 2018, Volume: 70, Number: 9, Pages: 1164-1173 Pages count : 10 DOI: 10.1111/jphp.12958

Authors

Borodina Tatiana ^1,2 , Marchenko Irina ^1,3 , Trushina Daria ^1,2,3 , Volkova Yulia ⁴ , Shirinian Valerii ⁴ , Zavarzin Igor ⁴ , Kondrakhin Evgeny ⁵ , Kovalev Georgy ⁵ , Kovalchuk Mikhail ^1,3 , Bukreeva Tatiana ^1,3

Affiliations

1	Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” of Russian Academy of Sciences, Moscow, Russia
2	Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
3	National Research Centre “Kurchatov Institute”, Moscow, Russia
4	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
5	Zakusov Institute of Pharmacology, Moscow, Russia

Objectives Anxiolytic drug zolpidem was incorporated into the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell. The release of zolpidem in saline solution and in polymer film modelling nasal mucosa was investigated. The anxiolytic effect of zolpidem upon intranasal administration of microcontainers and free medicine was determined by in vivo experiments on mice. Methods The structures of all compounds during zolpidem synthesis were established using nuclear magnetic resonance spectroscopy. The loading efficacy and release kinetics of zolpidem were analysed by spectrophotometry. Surface morphology of formulation was investigated by scanning electron microscopy. To determine the effect of zolpidem-loaded containers administration by the intranasal route in vivo experiments was carried out applying the open field test. Key findings Nasal administration of zolpidem in the form of the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell has a pronounced anxiolytic effect on the behaviour of the animals in the open field test. Conclusions The polyelectrolyte shell deposited together with zolpidem enhances the loading efficacy of the microcontainers. In vivo experiments on mice demonstrate increase in anxiolytic effect of zolpidem in microcontainers compared with upon intranasal administration of free medicine.

Borodina T. , Marchenko I. , Trushina D. , Volkova Y. , Shirinian V. , Zavarzin I. , Kondrakhin E. , Kovalev G. , Kovalchuk M. , Bukreeva T.
A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis, encapsulation and intranasal administration to mice
Journal of Pharmacy and Pharmacology. 2018. V.70. N9. P.1164-1173. DOI: 10.1111/jphp.12958 WOS Scopus OpenAlex

≡ Web of science:	WOS:000440841200004
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