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Delivery of Hydrophobic DrugsDelivery of Hydrophobic Drugs
By: Chandra Varney and Sophia Cai
Mentor: Tanja Homrichhausen
Dr. Michelle Bothwell
By: Chandra Varney and Sophia Cai
Mentor: Tanja Homrichhausen
Dr. Michelle Bothwell
INTRODUCTIONINTRODUCTION Scientists searching for a cure for Scientists searching for a cure for cancer must create drugs that can pass cancer must create drugs that can pass clinical trials. One obstacle is that the clinical trials. One obstacle is that the majority of cancer-fighting drugs are majority of cancer-fighting drugs are hydrophobic, while bloodstreams are hydrophobic, while bloodstreams are hydrophilic. In order to effectively mix the hydrophilic. In order to effectively mix the drug in your blood, emulsifiers must be drug in your blood, emulsifiers must be used to prevent the drug from grouping used to prevent the drug from grouping together. together. Even if an emulsifier works well, Even if an emulsifier works well, sometimes only a small amount of the sometimes only a small amount of the drug can be released into the bloodstream. drug can be released into the bloodstream. An effective cure has a balance between An effective cure has a balance between how well its emulsifier works and how how well its emulsifier works and how much of the actual drug is released.much of the actual drug is released.
Background: EmulsifiersBackground: Emulsifiers
Hydrophilic
Head
Hydrophobic TailSurfactan
t
Surfactants within a hydrophobic drug (heads are in the hydrophilic bloodstream).
Experiment 1:Experiment 1:Emulsifier Emulsifier
EffectivenessEffectiveness
1.1. Make buffer (fake blood) with a pH of 7.4.Make buffer (fake blood) with a pH of 7.4.
2.2. Homogenize buffer, drug (edible oil), and an Homogenize buffer, drug (edible oil), and an emulsifier. emulsifier.
3.3. Dilute mixture and test absorption level with a Dilute mixture and test absorption level with a Spectrophotometer after 1, 2, 3, 4, 5, and 10 Spectrophotometer after 1, 2, 3, 4, 5, and 10 minutes.minutes.
In the experiment, we tested different In the experiment, we tested different emulsifiers (Tween 80 and Lysozyme) to emulsifiers (Tween 80 and Lysozyme) to compare their effectiveness. We mixed an compare their effectiveness. We mixed an emulsifier with a hydrophobic drug and emulsifier with a hydrophobic drug and tested both the emulsifying activity and tested both the emulsifying activity and emulsion stability.emulsion stability.
1.1. Mixed hydrophobic drug with emulsifier Mixed hydrophobic drug with emulsifier (Tween 80) and dilute with buffer. (Tween 80) and dilute with buffer.
2.2. Put samples into Centrifuge to separate the Put samples into Centrifuge to separate the released drug from the oil (unused drug). released drug from the oil (unused drug).
3.3. Dilute with buffer and test absorption level. Dilute with buffer and test absorption level. 4.4. Compare results with a standard curve to see Compare results with a standard curve to see
how much of the drug was actually released. how much of the drug was actually released.
Experiment 2:Experiment 2:Drug Release RateDrug Release Rate
Ideally, the vast majority of the drug Ideally, the vast majority of the drug will be released into the bloodstream. will be released into the bloodstream. The speed of delivery can be chosen, The speed of delivery can be chosen, depending on the drug’s cause.depending on the drug’s cause.
DefinitionsDefinitionsEmulsifierEmulsifier – – substance that mixes a drug in the substance that mixes a drug in the
bloodstream (includes surfactants and proteins)bloodstream (includes surfactants and proteins)
SurfactantsSurfactants – – emulsifier that has a hydrophilic emulsifier that has a hydrophilic head and a hydrophobic tail; mixes drug quickly head and a hydrophobic tail; mixes drug quickly for a short amount of time (ex: Tween 80)for a short amount of time (ex: Tween 80)
ProteinProtein – – bulky emulsifier; mixes drug slowly, bulky emulsifier; mixes drug slowly, stabilizes quickly (ex: Lysozyme)stabilizes quickly (ex: Lysozyme)
HydrophobicHydrophobic – – “water hating,” attracts to other “water hating,” attracts to other hydrophobic substances (non-polar substance)hydrophobic substances (non-polar substance)
HydrophilicHydrophilic – – “water loving,” attracts to other “water loving,” attracts to other hydrophilic substances (polar substance)hydrophilic substances (polar substance)
HomogenizerHomogenizer – a tool that blends – a tool that blends substances togethersubstances together
SpectrophotometerSpectrophotometer – – tool that measures a tool that measures a liquid’s light absorption liquid’s light absorption
CentrifugeCentrifuge - - tool that separates molecules tool that separates molecules of different densities by spinning quicklyof different densities by spinning quickly
Emulsifying Activity Emulsifying Activity - - the mixed state the mixed state just after mixing the drug and bloodjust after mixing the drug and blood
Emulsion StabilityEmulsion Stability – – a measure of how a measure of how stable an emulsifier works by seeing how stable an emulsifier works by seeing how long it takes to reach emulsifier’s half lifelong it takes to reach emulsifier’s half life
Our EmulsifierOur Emulsifier
Combined Tween 80 and Lysozyme to Combined Tween 80 and Lysozyme to create our own emulsifier. Why?create our own emulsifier. Why?
• Tween 80 mixes the drug and blood Tween 80 mixes the drug and blood almost instantly, but slows down in a almost instantly, but slows down in a couple minutes. couple minutes.
• Lysozyme mixes the drug at a slow rate, Lysozyme mixes the drug at a slow rate, but stabilizes soon, instead of dropping but stabilizes soon, instead of dropping its mixing rate.its mixing rate.
• We created our own emulsifier with 75% We created our own emulsifier with 75% Tween 80 and 25% Lysozyme. We hoped Tween 80 and 25% Lysozyme. We hoped to create a drug that immediately mixes to create a drug that immediately mixes the drug and stabilizes before dropping the drug and stabilizes before dropping in speed.in speed.