Nanomedicines Flashcards
What are Nanomedicines?
Nanomedicine is the application of nanotechnology in the medical field, includes the development of nanostructures and nanoanalytical systems for medical applications. Also described as technologies under 1000nm
What is nano?
1 nm = 10^-9
What are nanoparticles?
Matters at the dimension between 1-1000 nm
What are the advantages of nanotechnologies?
– improved bioavailability, minimized toxic side effects, enhanced drug delivery, feasibility of incorporating other functions such as controlled release, imaging agents, targeting delivery, improving existing drug effectiveness, gene therapeutics , creating new types of pharmaceuticals and diagnostics
What are some other uses of nanomedicines?
apart from drug delivery, detection of molecules (diagnosis, biosensors)
For oral delivery, what size should nanoparticles be?
Smaller than 100 nm
For intravenous delivery what size should nanoparticles be?
Size range of 50-150 nm are considered optimal for circulation and accumulation
What are the types of nanoparticles?
Polymeric nanoparticles, lipid based nanoparticles, drug conjugates, hydrogel/colloid nanoparticles, carbon nanotubes, metal nanoparticles
When it comes to the delivery of active compounds, what is an issue with nanoparticles and how can this be combated?
The insufficient drug loading, often associated with uncontrolled drug release. Functionalizing the surface of conventional nanoparticle metals like gold or silver to carry drugs is an option to increase the drug loading
Why can metal nanoparticles carry relatively high drug doses?
because they can be synthesised in very small doses therefore they have large SA
What are the 2 methods used to prepare metal nanoparticles?
- Up-bottom methods, which typically require expensive equipment (e.g., high-energy laser to evaporate atoms from the surface of metals)
- chemical methods such as chemical, photochemical or electrochemical synthesis, microemulsion-mediated synthesis, seed-mediated synthesis and growth, or chemical vapour deposition
What are liposomes?
Small spherical systems that are synthesized from cholesterol and non-toxic phospholipids. Hydrophobic active molecules are encapsulated into the bilayer membrane
What are the 4 types of liposome?
conventional liposome, theranostic liposome, PEGylated liposome and ligand-targeted liposome
What do conventional liposomes improve?
Therapeutic index and toxicity
What do PEGylated liposomes improve?
stability and circulation time in bloodstream
What methods are used for the preparation of polymeric nanoparticles?
solvent evaporation, spontaneous emulsification, solvent diffusion, polymerization
Describe polymeric nanoparticles
made out of synthetic or natural polymers, have a matrix architecture composed of biodegradable and biocompatible polymers
Apart from steady drug release, what is another advantage of biodegradable nanoparticles
they do not accumulate in body
How are nanomedicines used in drug delivery and detection?
for protection and delivery of active ingredient, for release of therapeutic dose and in detection as a diagnostic tool to detect biomarkers, in imagining etc
What determines the biological performance of nanomedicines?
The nanomedicine’s dependent variables, particle size distribution, surface charge, and morphological characteristics
What are the 3 major interactions of nanomedicines?
biodistribution characteristics, cellular uptake to show efficacy, and finally clearance from the tissues
What happens nanomedicines after exposure to systemic circulation?
protein molecules adsorb forming an out shell around the particles , it can be fatal but also avoided by using low fouling coating such as PEG
Particles of what size are cleared through the kidneys?
10nm
How are bigger particles cleared?
Liver or mononuclear phagocyte system
What are some requirements for dosage forms used as injections?
aq solution, non-viscous, sterile, free from toxins, nanoparticles in size range 10 -1000nm (ideally 200nm)
Why is quality by design so beneficial?
enables the manufacturing of nanomedicines in a controlled and consistent fashion, maximizing their efficacy, used to meet the strict regulatory requirements for drug safety
How does QbD ensure product quality?
by testing of and control over the raw material quality, inflexible process design, rigid manufacturing process and product testing
What are the 4 manufacturing attributes used to design and produce nanoparticles?
material concentration, ratio of materials, target drug load, surfactant concentration
The 4 manufacturing attributes are used to determine what important quality attributes of nanoparticles?
size and shape, drug encapsulation efficiency/drug loading, polydispersity index, zeta potential/surface charge & drug release profile
When engineering nanoparticles, selecting the right materials and manufacturing method allows you to control what?
the shape and elastic modulus (stiffness) of nanoparticles to promote binding & internalization in cells
What is drug loading?
the ratio between the mass of the drug and the total mass of the drug loaded nanoparticles, critical parameter when making nanoparticles (typically low around 10%)
What is encapsulation efficiency?
A parameter more indicative of the manufacturing process, and defined as the ratio between the weight of the drug in the nanoparticles and the weight of the drug added during manufacturing (high values typically above 80%)
Why is poor drug loading bad?
difficult to achieve therapeutic window of a given component unless a high concentration of nanoparticles is used
Why is using a high conc of nanoparticles problematic?
Formulation can be viscous which is hard to inject
Do new manufacturing approaches to increase drug load use a lot of nanoparticles?
No they use the minimum amount to achieve required therapeutic levels
How can you prolong release of nanoparticles?
Drug-polymer conjugates can be synthesized and then used to fabricate the nanoparticles
How are liposomes obtained?
Extruded from membranes or obtained from emulsions
How is the release of compounds in liposomes controlled?
By the composition of the bilayer, and driven by its fluidity and/or rigidity
How is the delivery of a nanoparticle to a specific site of the body achieved?
by passive delivery or active targeting
Describe passive delivery
– achieved in the case of pathological conditions which cause the formation of gaps between endothelial cells. Nanomedicines with size 50-150 nm can enter through gaps and build up in the pathological region
Describe active targeting
nanomedicines are altered to reach a specific site for internalization and this done via surface modification of nanomedicines to hit the target, targets often membrane receptors on cells. Nanoparticles will build up in the diseased cell until it meets the therapeutic dose
Give an example of passive drug delivery
sterically stabilised liposome delivered drugs. Nonreactive liposomes are constructed of lipid bilayers that contain glycolipids or polyethylene glycol (PEG), which provide a steric barrier
What happen when chemotherapeutic drugs are encapsulated in sterically stabilised liposomes?
drug half-life and length of tumour cell exposure to drug increases
What are the 4 categories that drug release can be categorized into?
Diffusion (high initial release, then decreasing release rate with increasing diffusion distance), degradation of drug conjugate (dependent on MW, groups etc), release promoted by physical properties (stimuli controlled, such as pH, temperature etc) & swelling of the carrier material (solvent controlled. In osmosis controlled release, a semi-permeable polymeric membrane controls influx of solvent flows from outside to the drug-loaded core
