Nanoparticles Flashcards
What is a nanoparticle?
A particle on the nanoscale of 1 to 100 nanometres plus the interfacial layer including ions etc. The nanoparticles can be seen with an electron microscope
What two properties of nucleic acids need to be considered when making drug delivery systems?
Nucleic acids are negative charged due to the phosphate group in the backbone, and hydrophilic due to the sugar-phosphate backbone.
What are Some limitations of delivering naked small molecules, proteins and nucleic acids?
- Low cell uptake (if the drug needs to be internalised to take effect)
- Short blood circulation time (except monoclonal antibodies)
- Rapid degradation in physiological fluids
- Lack of cell specificity
Give FOUR example of viral vectors used to enhance drug delivery
Adenoviruses (nonenveloped, without an outer lipid bilayer)
Adeno-associated viruses
Retroviruses
Lentiviruses
What are the advantages and disadvantages of viral vectors for drug delivery?
Advantages: efficient cell uptake, endosomal escape
Disadvantages: immunogenicity, low cell specificity, limited packaging capacity, difficult to produce
Why are non-viral vectors used? What are their advantages?
To overcome limitations of viral vectors Advantages: Lower immunogenicity Patients don’t have pre-existing immunity Lager payloads- more drugs packed in Easier to synthesize
How can liposomes be used are drug delivery systems?
Made of lipids which is similar to cell membranes
Phosphatidylcholine and phosphatidylserine – two major components of cell membrane chloride (DOTMA) is an amphiphilic molecule for making liposome
An amphiphilic molecule (a compound that possesses both hydrophilic and lipophilic moieties)
Hydrophobic tails face inward away from the aqueous solution while hydrophilic heads are in contact with the solution
What are polymersomes?
similar to liposomes but made from amphiphilic polymer molecules not lipid molecules. Will self assemble in aqueous solution.
What are catatonic polymers?
Positively charged PEI can condense negatively charged nucleic acids to form polyplexes (spherical or doughnut-shaped nanoparticulate complexes). In addition, the positive charge can also help the binding of polyplexes to cell membrane which is negatively charged.
What are cell penetrating peptides?
They are peptides with exploit the micropinocytosis mechanism of action
What is an example of a degradable polymer nanoparticle and how are they made?
Poly(lactic-co-glycolic acid) (PLGA)
Double Emulsion-
Drug water solution dispersed in the polymer organic solvent phase then mixture is poured into more water with polyvinyl alcohol as a surfactant to stabilise the dispersant system, organic solvent evaporate and cause hardening of polymer the drug loaded nanoparticles will form
How can magnetic nanoparticles be used?
Mixing iron salts with bas to form iron oxide, magnetic nanoparticles can be coated with drugs
Advantages of magnetic nanoparticles
a magnetic field can be used to direct the external magnetic field i.e. to a tumour.
Nanoparticles larger than 10nm usually impedes their diffusion through the small vascular pores of normal/healthy endothelium.
Due to the leaky vasculature in tumours, Nanoparticles up to ̴700nm can penetrate through the endothelium.
How can the blood circulation time be increased?
Fusion of Fc fragment of antibody with the drug can use DNA recombinant technology, longer circulation time as proteins can be internalised by utilising the neonatal Fc receptor recycling pathway.
How can PEGylation increase blood circulation time?
Drug or vehicle/ liposome is conjugated to PEG,
- PEG molecules are highly hydrated which increases the hydrodynamic radius of the conjugate, hence reduce renal filtration
- prevents uptake and clearance by mononuclear phagocyte system,
- decreases the formation of neutralizing antibodies against a protein drug by masking antigenic sites
- offers protection from proteolytic enzymes such as trypsin, chymotrypsin, and proteases
