Messenger ribonucleic acid (mRNA) – Vaccine production
mRNA vaccine - Administration
mRNA vaccine – Absorption and cellular response
mRNA vaccine – Distribution and immune response
mRNA vaccine – Delivery by nano-capsules
Why can‘t we deliver the mRNA naked?
▪ mRNA lacks passive diffusion across cell membranes (high 𝑀𝑊, negative charge)
▪ mRNA is rapidly degraded by extracellular Rnases preventing its efficient delivery and efficacy
—> improvement of cellular uptake & cargo protection
What is drug delivery and why is it important?
Drug delivery definition: Method by which a drug is administered to achieve a therapeutic effect
Why is it important?
Control over administration type and therefore place, time and rate of drug release
Protection against degradation and therefore increase in drug efficacy
Facilitation of barrier permeation by positive interaction between drug vehicle and barrier
Minimization of side effects
Enabling long-term storage
Pharmacokinetics – The path of drugs within the human body
Absorption – Administration routes
Absorption – Important considerations for drug administration
Absorption – Parenteral Administration
Absorption – Enteral administration
Absorption – Bioavailability
Distribution – General body compartments
Distribution – 2-compartment model with intravascular dose
Distribution – Non-idealities
Non-idealities:
Barrier permeability
Drug properties: molecular size, charge, hydrophobicity
Interactions between multiple drugs
Plasma Protein Binding (PPB) / Tissue Protein Binding (TPB)
pH of the compartment
Pathological / Physiological conditions
Differences in blood flow
Distribution – Apparent volume of distribution
Metabolism – Dependency on the route of administration
Metabolism – Elimination of a compound
Excretion
Pharmacokinetics - Summary
Pharmacokinetic profile and the therapeutic window (TW)
Controlled drug release by nano-particles (NPs)
Opsonization and Phagocytosis determine particle circulation time
NP properties and their influence on pharmcokinetics
The problem with protein adsorption
NP properties – surface charge
NP properties – particle size
NP size influences:
▪ Cell internalization
▪ Biodistribution
▪ Circulation time / Clearance
NP properties – particle shape
Overview of possible drug nano-carriers
Fatty acid- and lipid-based drug NPs
Industrial production of liposomes by ethanol injection
Industrial production of SLNP
Extracellular vesicles (EVs)
Polymeric NPs - Microgels
Polymeric NPs – Polyelectrolyte complex particles (PECP)
Polymeric NPs - Dendrimer
Polymeric NPs – Dendrimersomes & polymersomes
Inorganic NPs – Gold particles (AuNPs)
Inorganic NPs – Silica particles
Inorganic NPs – Carbon-based particles
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