Intranasal drug delivery: opportunities and toxicologic challenges during drug development

被引:349
作者
Keller, Lea-Adriana [1 ,2 ]
Merkel, Olivia [2 ]
Popp, Andreas [1 ]
机构
[1] AbbVie Deutschland GmbH & Co KG, Preclin Safety, Knollstr, D-67061 Ludwigshafen, Germany
[2] Ludwig Maximilians Univ Munchen, Dept Pharm Pharmaceut Technol & Biopharm, Butenandtstr 5-13, D-81337 Munich, Germany
关键词
Intranasal drug delivery; Olfactory pathways; Nose-to-brain-delivery; Nasal toxicity; NASAL MUCOCILIARY CLEARANCE; GERM AGGLUTININ-HORSERADISH; CILIARY BEAT FREQUENCY; CENTRAL-NERVOUS-SYSTEM; RAT OLFACTORY SYSTEM; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; STEM-CELLS; BENZALKONIUM CHLORIDE; RESPIRATORY MUCOSA;
D O I
10.1007/s13346-020-00891-5
中图分类号
TH7 [仪器、仪表];
学科分类号
0804 ; 080401 ; 081102 ;
摘要
Over the past 10 years, the interest in intranasal drug delivery in pharmaceutical R&D has increased. This review article summarises information on intranasal administration for local and systemic delivery, as well as for CNS indications. Nasal delivery offers many advantages over standard systemic delivery systems, such as its non-invasive character, a fast onset of action and in many cases reduced side effects due to a more targeted delivery. There are still formulation limitations and toxicological aspects to be optimised. Intranasal drug delivery in the field of drug development is an interesting delivery route for the treatment of neurological disorders. Systemic approaches often fail to efficiently supply the CNS with drugs. This review paper describes the anatomical, histological and physiological basis and summarises currently approved drugs for administration via intranasal delivery. Further, the review focuses on toxicological considerations of intranasally applied compounds and discusses formulation aspects that need to be considered for drug development.
引用
收藏
页码:735 / 757
页数:23
相关论文
共 260 条
[31]   A QUANTITATIVE STUDY OF ANTEROGRADE AND RETROGRADE AXONAL-TRANSPORT OF EXOGENOUS PROTEINS IN OLFACTORY NERVE C-FIBERS [J].
BUCHNER, K ;
SEITZTUTTER, D ;
SCHONITZER, K ;
WEISS, DG .
NEUROSCIENCE, 1987, 22 (02) :697-707
[32]   A NOVEL MULTIGENE FAMILY MAY ENCODE ODORANT RECEPTORS - A MOLECULAR-BASIS FOR ODOR RECOGNITION [J].
BUCK, L ;
AXEL, R .
CELL, 1991, 65 (01) :175-187
[33]   Localization of orexins and their receptors in the rat olfactory system:: possible modulation of olfactory perception by a neuropeptide synthetized centrally or locally [J].
Caillol, M ;
Aïoun, J ;
Baly, C ;
Persuy, MA ;
Salesse, R .
BRAIN RESEARCH, 2003, 960 (1-2) :48-61
[34]  
Calaf, 2000, RANDOMIZED COMP INTR, V96, P7
[35]   Meta-analysis: Efficacy and safety of inhaled insulin therapy in adults with diabetes mellitus [J].
Ceglia, Lisa ;
Lau, Joseph ;
Pittas, Anastassios G. .
ANNALS OF INTERNAL MEDICINE, 2006, 145 (09) :665-675
[36]   A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment [J].
Chamanza, R. ;
Wright, J. A. .
JOURNAL OF COMPARATIVE PATHOLOGY, 2015, 153 (04) :287-314
[37]   Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development [J].
Chen, Thomas C. ;
da Fonseca, Clovis O. ;
Schonthal, Axel H. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (12)
[38]   ALLELIC INACTIVATION REGULATES OLFACTORY RECEPTOR GENE-EXPRESSION [J].
CHESS, A ;
SIMON, I ;
CEDAR, H ;
AXEL, R .
CELL, 1994, 78 (05) :823-834
[39]   Requirement for slit-1 and robo-2 in zonal segregation of olfactory sensory neuron axons in the main olfactory bulb [J].
Cho, Jin Hyung ;
Lepine, Manon ;
Andrews, William ;
Parnavelas, John ;
Cloutier, Jean-Francois .
JOURNAL OF NEUROSCIENCE, 2007, 27 (34) :9094-9104
[40]   Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats [J].
Choi, Hye-Yeon ;
Lee, Yong-Hoon ;
Lim, Cheol-Hong ;
Kim, Yong-Soon ;
Lee, In-Seop ;
Jo, Ji-Min ;
Lee, Ha-Young ;
Cha, Hyo-Geun ;
Woo, Hee Jong ;
Seo, Dong-Seok .
PARTICLE AND FIBRE TOXICOLOGY, 2020, 17 (01)