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Nose-to- brain delivery of small molecule drugs: Formulation development studies
Portugal ( PorMSIC) - University Beira Interior, Covilha
Faculdade de Ciencias da Saude Av. Infante D. Henrique 6200-506 Covilha Portugal
Luis Taborda Barata
Adriana Oliveira dos Santos
Type of Research Project
- Basic science
What is the background of the project?
Intranasal drug administration has many potential advantages and is of particular interest in drugs acting on the brain and when a rapid effect is required. Epileptic convulsions are one of such cases, but usually require parenteral drugs only administered by qualified professionals, wlyle intranasal administration could be achieved by relatives/undifferentiated caregivers as a first line response. The challenge of nasal drug formulations, however, is to promote sufficient and reproducible drug disposition or sufficient brain targeting to overcome systemic adverse effects or to achieve therapeutic efficacy from small administered doses. Adequate and innovative formulation is key in achieving these goals.
What is the aim of the project?
To formulate and characterize (in vitro, ex vivo, in vivo) antiepileptic intranasal drug formulations.
What techniques and methods are used?
Formulation strategies under development include nanoemulsions, in situ gel-forming formulations, pro-drugs, association of drug and respective prodrugs, among other possibilities. In vitro characterization of formulations include evaluation of pH, viscosity, osmolality, particle/drop size dispersion, gelling temperatures, solubility, drug assays (liquid chromatography). Ex vivo experiment are used to evaluate permeation and bioconversion of drugs in nasal mucosa. In vivo, bioavailability and brain targeting is derived from pharmacokinetic and biodistribution studies in rats.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
What are the tasks expected to be accomplished by the student?
Both in vitro or ex vivo experiments are adequate for the participation of the student, after initial observation and training, if the same procedures are used repeatedly during that time. Collection of bibliographic data/information eventually required to support an assay under development or a decision to be taken about the project direction/to solve a problem that may arise can be performed independently.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Capacilty to team work, basic laboratory skils (rigourous preparation of solutions handling pipetes, micropipetes, balances, etc;) experiemntal data interpretaion skils, computer skils (database search, excel...)
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Students in biomedical fields - Dental medicine students (IADS members)
- Development and application of an ex vivo fosphenytoin nasal bioconversion/permeability evaluation method. Antunes Viegas D; Rodrigues M; Francisco J; Falcao A;?Alves G; Santos AO. Eur J Pharm Sci. 2016 Jun 30;89:61-72. doi: 10.1016/j.ejps.2016.04.018. PMID:27106504
- Direct nose-to- brain delivery of lamotrigine following intranasal administration to mice. Serralheiro A;?Alves G; Fortuna A; Falcao A. Int J Pharm. 2015 Jul 25;490(1-2):39- 46. doi: 10.1016/j.ijpharm.2015.05.021. PMID: 25979854
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