Drug Delivery to the Central Nervous System (CNS)

Course content

Initial lectures will give an overview of the history of brain drug delivery. This will be followed by lectures describing brain anatomy, blood-brain and blood CSF barriers. The physicochemical parameters necessary for brain drug permeation will be treated in detail, along with a detailed description of the tissue barrier properties. Brain efflux transporters and their substrate profiles will be dealt with. This will be followed by a detailed treatise of brain uptake transporters, brain drug metabolism and the use of in vitro models in predicting CNS drug uptake. The pharmacokinetic concepts specific for brain delivery will be introduced, including the importance of estimating protein binding in plasma and brain tissue. Single dosing and steady-state concepts will be covered. The translational aspects of preclinical studies will discussed, with focus on the low predictability between animal models and human patients. The pathology of some common brain diseases will be treated, and the implications for drug delivery for a given disease will be discussed. Biologics and Drug delivery systems for CNS treatment will also be covered.

Education

MSc Programme in Medicinal Chemistry - elective

MSc Programme in Pharmacy (Danish programme cand.pharm) - elective

MSc Programme in Pharmaceutical Sciences (Danish programme cand.scient.pharm) - restricted elective

MSc Programme in Pharmaceutical Sciences (English programme) - restricted elective

Learning outcome

The main objective of the course is to introduce the basic concepts and methods in CNS drug delivery and provide an overview of the different approaches used by academia and industry in the field. The course consists of lectures, discussion classes with student presentations and a final exam. At the end of the course, the students are expected to be able to:

At the end of the course the students are expected to be able to:

Knowledge

  • describe how physicochemical properties of a compound relates to its likelihood to become a CNS drug compound
  • describe the methods available for estimating brain efflux properties
  • describe the molecular properties of the blood-brain barrier
  • define the rate limiting steps in brain drug delivery
  • demonstrate knowledge on how brain pathologies may alter brain drug disposition
  • explain how CNS drug candidates are tested in vitro and in vivo
  • identify the pharmacokinetics of drug compound disposition to the brain
  • reflect on the concept and importance of free-versus bound drug compound concentrations in brain and blood.

 

Skills

  • deduct if a drug compound is suited for CNS delivery according to its physicochemical properties.
  • use Michaelis-Menten kinetics to estimate transporter activity and inhibition
  • interpret data from in-vitro test models for CNS barrier permeability and efflux, using permeability estimates and efflux ratio's
  • Read, understand and extract general conceptual knowledge from original research articles

 

Competencies

  • integrate knowledge from organic chemistry, formulation, physical chemistry, pharmacokinetics, tissue barrier biology and pharmacology to design formulations for brain drug delivery.
  • apply simple mathematical models for predicting and describing brain drug uptake and efflux from both in vivo and in vitro studies.

Lectures and discussion classes, where students present selected parts of the curriculum to each other.

The course will be based on selected original research articles and chapters  from the following textbooks:

  • "Drug Delivery to the Brain - Physiological Concepts, Methodologies and Approaches" by Hammarlund-Udenaes, Margareta, de Lange, Elizabeth, Thorne, Robert G. (Eds.) AAPS Advances in the Pharmaceutical Sciences Series.
  • “Molecular Biopharmaceutics - Aspects of Drug Characterisation, Drug Delivery and Dosage Form Evaluation” by Bente Steffansen, Birger Brodin and Carsten Uhd Nielsen(Eds.) (Pharmaceutical Press).

 

Teaching is based on the assumption that the students have acquired knowledge, skills and competences corresponding to those obtained by completion of the first five semesters of the BSc Programme in Pharmacy.

Oral
Collective
Continuous feedback during the course of the semester
Peer feedback (Students give each other feedback)
ECTS
7,5 ECTS
Type of assessment
On-site written exam, 2 hours under invigilation
Type of assessment details
The examination will deal with selected broad questions regarding brain drug delivery. Background material will be the curriculum.
Part of the exam will test the students ability to extract knowledge from an original scientific article provided at the exam.
Aid
Written aids allowed

Find more information about written on-site exams in the exam rooms, incl. information about standard programs on the exam PCs at KUnet

Kandidat i farmaci - KUnet

In addition to the standard programs digital notes are permitted for this exam. It is allowed to upload notes for the ITX exam via digital exam. You will find a link to this feature from your exam in Digital Exam.

Marking scale
7-point grading scale
Censorship form
No external censorship
Criteria for exam assessment

To achieve the grade 12 the student must be able to:

Knowledge

  • describe how physicochemical properties of a an API relates to its likelihood to become a CNS drug compound
  • describe the methods available for estimating brain efflux properties
  • describe the molecular properties of the blood-brain barrier
  • define the rate limiting steps in brain drug delivery
  • demonstrate knowledge on how brain pathologies may alter brain drug disposition
  • explain how CNS drug candidates are tested in vitro
  • identify the pharmacokinetics of drug compound disposition to the brain
  • reflect on the concept and importance of free-versus bound drug compound concentrations in brain and blood.

 

Skills

  • deduct if a drug compound is suited for CNS delivery according to its physicochemical properties.
  • use Michaelis-Menten kinetics to estimate transporter activity and inhibition
  • interpret data from in-vitro test models for CNS barrier permeability and efflux, using permeability estimates and efflux ratio's
  • read, understand and extract general conceptual knowledge from original research articles

 

Competencies

  • integrate knowledge from organic chemistry, formulation, physical chemistry, pharmacokinetics, tissue barrier biology and pharmacology in order to design formulations for brain drug delivery.
  • apply simple mathematical models for predicting and describing brain drug uptake and efflux from both in vivo and in vitro studies.
  • Rapidly read and identify the key messages of original scientific articles

Single subject courses (day)

  • Category
  • Hours
  • Lectures
  • 20
  • Preparation
  • 156
  • Theory exercises
  • 28
  • Exam
  • 2
  • English
  • 206

Kursusinformation

Language
English
Course number
SFKKIF103U
ECTS
7,5 ECTS
Programme level
Full Degree Master
Duration

1 block

Placement
Block 3
Schedulegroup
C
Capacity
70 students - 9 seats reserved for master students and 1 seat reserved for an international master student.
Studyboard
Study Board of Pharmaceutical Sciences
Contracting department
  • Department of Pharmacy
Contracting faculty
  • Faculty of Health and Medical Sciences
Course Coordinator
  • Mie Kristensen   (14-77736f38757c737d7e6f787d6f784a7d7f786e38757f386e75)
Saved on the 08-10-2024

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