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MD25 Controlling release in vivo
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1Temporal control could be important for drugs which:
• Have a time-dependent [blank_start]mechanism of action[blank_end] eg some cytotoxic drugs, [blank_start]antibiotics[blank_end]
• Are [blank_start]unstable[blank_end] (short half life)
• Need continuous [blank_start]exposure[blank_end]
• Need [blank_start]multiple[blank_end] short periods of exposure- Amechanism of action
- Bantibiotics
- Cunstable
- Dexposure
- Emultiple
2Spatial control could be important for drugs which are:
• Highly [blank_start]toxic[blank_end], and have a [blank_start]narrow[blank_end] therapeutic window
• Readily [blank_start]metabolized or excreted[blank_end]
• Have a [blank_start]concentration-dependent[blank_end] mechanism of action- Atoxic
- Bnarrow
- Cmetabolized or excreted
- Dconcentration-dependent
3A time-dependent mechanism of action means that the amount of [blank_start]time spent[blank_end] above the [blank_start]therapeutic level[blank_end] is more important than the peak drug concentration. Examples are some classes of antibiotics, and [blank_start]cycle specific cytotoxic[blank_end] cancer drugs.
A concentration-dependent mechanism of action means [blank_start]peak concentration[blank_end] reached is more important than time spent above therapeutic level. Examples are [blank_start]non-cycle specific[blank_end] cytotoxic drugs (chemotherapy) & [blank_start]concentration-dependent killing[blank_end] antibiotics. Also known as ‘[blank_start]log kill[blank_end]’ agents.- Atime spent
- Btherapeutic level
- Ccycle specific cytotoxic
- Dpeak concentration
- Enon-cycle specific
- Fconcentration-dependent killing
- Glog kill
4As dose is increased, non-cycle specific cytotoxic drugs become more effective.
- ATrue
- BFalse
5As duration of drug exposure is increased, cycle specific cytotoxic drugs become more effective.
- ATrue
- BFalse
6We can achieve controlled release in vivo by using prodrugs, IDDS, nanomedicines and nanoformulations. We can use nano-scale materials for therapeutic benefit, to modify [blank_start]kinetics[blank_end] of release (temporal control) – [blank_start]sustained or pulsatile[blank_end], [blank_start]location[blank_end] of release (spatial control) – crossing [blank_start]barriers[blank_end] (eg BBB, cell membrane, nuclear membrane), or at tissue [blank_start]site[blank_end] (eg tumor). We can therefore increase [blank_start]therapy efficacy[blank_end] and decrease [blank_start]side effects[blank_end] (drug toxicity and antibiotic resistance).
- Akinetics
- Bsustained or pulsatile
- Clocation
- Dbarriers
- Esite
- Ftherapy efficacy
- Gside effects
7Why use Nanoparticles?
• Increase [blank_start]solubility[blank_end]
• [blank_start]Protect[blank_end] active(s)
• [blank_start]Co-delivery[blank_end] of multiple drugs
• To control [blank_start]time[blank_end] of release (temporal)
• To control [blank_start]location[blank_end] of release (spatial)- Asolubility
- BProtect
- CCo-delivery
- Dtime
- Elocation
8The [blank_start]immune[blank_end] system has evolved to recognise and take up nm – µm complexes. This is bad for [blank_start]drugs[blank_end], though good for [blank_start]vaccines[blank_end]. Commonly we use ‘[blank_start]stealth[blank_end]’ technologies, eg coating NPs with [blank_start]polyethylene glycol[blank_end]; known as PEGylation.
- Aimmune
- Bdrugs
- Cvaccines
- Dstealth
- Epolyethylene glycol
9Tumour blood vessels are [blank_start]leaky[blank_end] so we can give [blank_start]passive[blank_end] tumor specific delivery by making NPs too [blank_start]large[blank_end] to leak through healthy vessels, but which will [blank_start]diffuse[blank_end] into tumors. This does depend on [blank_start]pressure[blank_end] inside the tumor - it may get leakage back out of the tumor into the blood vessel.
- Aleaky
- Bpassive
- Clarge
- Ddiffuse
- Epressure
10The half life of Peg-Dox is 55 hours, compared to 10 min for Dox, so it does
not need to be given by continuous infusion (CI).- ATrue
- BFalse
11We can achieve passive spatial control by modifying the [blank_start]intrinsic[blank_end] properties of the nanoformulation, such as nanoparticle [blank_start]size, shape, charge, and hydrophobicity[blank_end].
We can achieve active spatial control by placing [blank_start]external markers[blank_end] on our liposomes/nanoparticles like [blank_start]antibodies, aptamers, and ligands[blank_end].- Aintrinsic
- Bsize, shape, charge, and hydrophobicity
- Cexternal markers
- Dantibodies, aptamers, and ligands
12Temporal control passive release:
Delivering drug in a nanoformulation can increase [blank_start]circulation time[blank_end] and give [blank_start]sustained[blank_end] release, if we can [blank_start]avoid[blank_end] uptake by the immune system. Release will depend on particle [blank_start]composition & stability[blank_end], and can be via [blank_start]diffusion, erosion, or osmotic pumping[blank_end].
Temporal Control active release:
[blank_start]Stimuli responsive[blank_end] nanoformulations which release drug upon [blank_start]exposure[blank_end] to an endogenous or exogenous stimuli.- Acirculation time
- Bsustained
- Cavoid
- Dcomposition & stability
- Ediffusion, erosion, or osmotic pumping
- FStimuli responsive
- Gexposure
13Temporal control: Passive release is [blank_start]triphasic:[blank_end]
1. Burst of drug at/near [blank_start]surface[blank_end]
2. Slow release by [blank_start]diffusion[blank_end]
3. Burst due to [blank_start]erosion, breakdown, degradation[blank_end]- Atriphasic
- Bsurface
- Cdiffusion
- Derosion, breakdown, degradation
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- PHCY211 (Medicines) Quiz on MD25 Controlling release in vivo, created by Mer Scott on 27/05/2018.
- Author
- Mer Scott
- Language
- English
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