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New Opportunity to Formulate Intranasal Vaccines and Drug Delivery Systems Based on Chitosan.

ABSTRACT: In an attempt to develop drug delivery systems that bypass the blood-brain barrier (BBB) and prevent liver and intestinal degradation, it was concluded that nasal medication meets these criteria and can be used for drugs that have these drawbacks. The aim of this review is to present the influence of the properties of chitosan and its derivatives (mucoadhesion, permeability enhancement, surface tension, and zeta potential) on the development of suitable nasal drug delivery systems and on the nasal bioavailability of various active pharmaceutical ingredients. Interactions between chitosan and proteins, lipids, antigens, and other molecules lead to complexes that have their own applications or to changing characteristics of the substances involved in the bond (conformational changes, increased stability or solubility, etc.). Chitosan and its derivatives have their own actions (antibacterial, antifungal, immunostimulant, antioxidant, etc.) and can be used as such or in combination with other molecules from the same class to achieve a synergistic effect. The applicability of the properties is set out in the second part of the paper, where nasal formulations based on chitosan are described (vaccines, hydrogels, nanoparticles, nanostructured lipid carriers (NLC), powders, emulsions, etc.).

SUBMITTER: Popescu R

PROVIDER: S-EPMC7404068 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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New Opportunity to Formulate Intranasal Vaccines and Drug Delivery Systems Based on Chitosan.

Popescu Roxana R Ghica Mihaela Violeta MV Dinu-Pîrvu Cristina-Elena CE Anuța Valentina V Lupuliasa Dumitru D Popa Lăcrămioara L

International journal of molecular sciences 20200716 14

In an attempt to develop drug delivery systems that bypass the blood-brain barrier (BBB) and prevent liver and intestinal degradation, it was concluded that nasal medication meets these criteria and can be used for drugs that have these drawbacks. The aim of this review is to present the influence of the properties of chitosan and its derivatives (mucoadhesion, permeability enhancement, surface tension, and zeta potential) on the development of suitable nasal drug delivery systems and on the nas ...[more]

PMID: 32708704

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Project description:We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and morbidity arising from infection with HPAI H5N1 virus.

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New Opportunity to Formulate Intranasal Vaccines and Drug Delivery Systems Based on Chitosan.

Publications

New Opportunity to Formulate Intranasal Vaccines and Drug Delivery Systems Based on Chitosan.

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