Saving Lives with Solubility Grades: 7th-8th Time: About 2 hours per activity Objectives: Students will learn and apply fundamental physical science principles to design a carrier for a hydrophobic drug. Additionally, students will be introduced to the applications of controlling solubility in everyday items including medicine, food, and cosmetics. Concepts illustrated to students in these activities include solubility, surface tension, phase change, phase separation, the engineering design process, and polar vs. nonpolar compounds. This lesson is intended to integrate basic physical science and chemistry principles with the National Academy of Engineering's Grand Challenges; specifically, engineering better medicines. Arizona 8th Grade Science Standards: • S1C1: Observations, Questions, and Hypotheses (PO 1, 3) • S1C2: Scientific Testing (PO 1,3,4,5) • S1C3: Analysis and Conclusions (PO 1,3,5) • S2C2: Nature of Scientific Knowledge (PO 1,2,3,4) • S3C2: Science and Technology in Society (PO 1,2,3) • S5C1: Properties and Changes of Properties in Matter (PO 2,4,5,6,7) Materials: Activity #1: Water Oil Test tubes Hot Plate Salt Sugar Hand Soap Milk (Skim & Whole) Baking Soda Toothpaste Hot Sauce Vaseline "Bubbles" solution Activity #2: Craft supplies, sticky tack 1 Procedures: Activity #1: Making Bubbles ... of Water Make and show students a stabilized emulsion (Water, Oil, and Soap) or (better yet) some polymer or glass microspheres suspended in water. Use a microscope to prove the shape of the spheres if they are not easy to see with the naked eye. Conduct a discussion on how the particles or bubbles could be made to be so small and yet perfectly round. If necessary, provide the hint that they can be made using oil and water, which usually will separate into two layers. Ask them what could possibly make spheres without this separation occurring. Likely, many of the suggestions proposed by students will be included in the activity. For the activity itself, students need to prepare a test tube with 1:1 water:oil by volume (about 5 mL each is good). Provide the different treatment options for materials that can be added to the tubes (or others depending on the suggestions of the class) and let students choose 3 or 4 to test on their own. Options include salt, sugar, soap, toothpaste, milk, vaseline, hot sauce, "bubbles," or whatever else you have available. A small amount of the substance should then be added to the oil and water. After adding one material, students will stir or shake the solution for a set amount of time. Encourage students to use the same shaking or stirring method and time for each sample. After each trial, students will record data on a worksheet. It is important to wait at least 2 minutes after mixing to tell if the bubbles are truly stable or if the water and oil are separating slowly. The students should also try first without adding any material. Following the lab, lead a discussion either with the class or in small groups discussing the chemical structure of each additive and then relating that to the results of the students' experiments. Questions could include: What does the salt "like"? What does the vaseline "like"? Why do the ones that make bubbles work? Why would we want to make microspheres? Why would we want water and oil to not separate? What could we use that for? There are basically 4 classes of materials: polar, non-polar, mixtures of both, and surfactants (the ones that make oil and water "mix"!). 1) Polar materials, like salt, prefer water to oil because they have charges. An analogy for students could be that water is like a battery or a magnet and it has positive and negative ends to it. Salt dissolves because water dissolves materials which also have charges. This is why magnets stick to other magnets but not to something inert like modeling clay. 2) Non-polar materials, like vaseline. Students will describe these as greasy or oily. Exactly opposite of the salt, these will mix with oil but not with water. 3) Mixtures of both, like hot sauce. Hot sauce has some salt and spices which are polar, and some chili oil which is non-polar. Students will see the components (by their color) extract into both phases. 4) Surfactants. These should lead to bubbles and the water and oil will blend into one big phase containing lots of very tiny bubbles. This is a good lab to introduce polar vs. non-polar bonding. The compounds that make bubbles, such as soap and toothpaste, are special because they have molecules in them that have a polar segment and a non-polar segment. For example, sodium 2 lauryl sulfate (shown in the figure at left) is a common component of many soaps, detergents, and toothpastes. The molecule works by the left non-polar side (full of nonpolar C-H bonds) dissolving in the oil/dirt/grease and the right polar side (containing charges) dissolving in water. The oil then becomes mixed with the water in a little bubble structure as shown in the figure at right. We use this type of molecule (called a surfactant) for many things. Some key examples are soap, detergents, toothpaste, lotions, ointments (such as Neosporin to get polar antibiotics into oily skin), and foods such as milk. In fact, the reason that wet ingredients for baking often include milk and eggs is that these materials prevent oily ingredients and watery ingredients from separating. Perhaps the most important application is that cell membranes is made up of a double surfactant layer, with water on either side and an oily phase in the middle. These layers prevent small polar particles (such as sodium and potassium ions) from traveling freely in and out of cells. Another analogy that may be useful for students for this activity is raindrops on the window of a car. As they fall down the window, drops will quickly combine with other drops and become bigger. Similarly, after shaking oil and water, similar droplets "find each other", combine, and settle out. Surfactants create a protective barrier around each droplet or bubble, so the droplets just bump into each other and do not combine. A related topic is that when two phases do not like each other, surface tension causes phases to separate to minimize the contact between the phases. Including video demonstrations from the internet of liquid-liquid or liquid-air interfaces (such as water bubbles in zero gravity) are visual and interesting. Assessment for this activity can be based on the detail and accuracy of students' worksheets as well as their participation in the pre and postlab discussions. There is a worksheet available for this activity. 3 Activity #2: Designing a Drug Carrier After discussing the "like-dissolves-like" concepts in Activity 1, present students with the following design/engineering problem. Pretend that you have to make a carrier for an oily cancer drug molecule so that the drug can dissolve in the body which is mostly made of water. How can you "trick" the water in the body into dissolving the drug? There's no limit to what you can put on your carrier or whether it is possible. How big do you think it would really have to be? Draw the molecules as lines or shapes. You don't have to say what the molecules are, but label which parts are polar and what parts are nonpolar. What has to be near the drug? What about the water part? Some optional guidance or hints for students: Drug must be dissolved in an oily phase. The carrier has to "make the body think" that water "likes it" or will dissolve it. If a student finishes quickly, challenge them to add other functions in that we might want in a drug for treating a specific disease. For example, targeting and imaging are also often incorporated so the drug knows to go to a particular place or can be tracked by X-rays to see if it went where it was supposed to go. Arrange students in groups and have them discuss their designs. Let the groups pick a design together and then build the carrier out of craft supplies. Groups will then present to the rest of the class on how the carrier works and any special features their carrier has. Peer assessment can be used for this activity. Each group can grade another group's design and write 2-3 sentences explaining their thoughts on the design (advantages/disadvantages). A postlab discussion can follow on the real world applications of drug carriers. Examples for applications of these drug carriers already being used include liposomal drug formulations (for cancer), nanoemulsions being used as vaccines, micelles (for cancer), polymer-drug conjugates (for macular degeneration), and microspheres (drug capsules, pore-forming agents, cosmetics). This problem is real. Cancer drugs already exist which can kill cancer cells very effectively. The problem is that it is difficult to get cancer drugs to get into the watery environment of the body and then to only go to the tumor because the drugs are also good at killing normal cells. Depending on the students, you might also introduce some figures about jobs, funding, and expected growth in the field of biomedical engineering. Many problems in this field remain unsolved. 4