TY - JOUR

T1 - A novel formulation of zolpidem for direct nose-to-brain delivery

T2 - synthesis, encapsulation and intranasal administration to mice

AU - Borodina, Tatiana

AU - Marchenko, Irina

AU - Trushina, Daria

AU - Volkova, Yulia

AU - Shirinian, Valerii

AU - Zavarzin, Igor

AU - Kondrakhin, Evgeny

AU - Kovalev, Georgy

AU - Kovalchuk, Mikhail

AU - Bukreeva, Tatiana

N1 - Publisher Copyright: © 2018 Royal Pharmaceutical Society

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

KW - anxiolytic effect

KW - intranasal delivery

KW - microcontainers

KW - zolpidem

UR - http://www.scopus.com/inward/record.url?scp=85051105425&partnerID=8YFLogxK

U2 - 10.1111/jphp.12958

DO - 10.1111/jphp.12958

M3 - Article

C2 - 29956328

AN - SCOPUS:85051105425

VL - 70

SP - 1164

EP - 1173

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 9

ER -