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Drug Delivery with Polymer Based Nanoparticles

Grades: 9
Author: Joanna Price
Source: This material is based upon work supported by the National Science Foundation under Grant No. EEC-1161732.


Abstract

Students will critique common drug delivery techniques and analyze ways that newer nanotechnology techniques could be more beneficial for drug delivery. The students will be responsible for investigating the properties needed for nanoparticles to be used in biological systems in order for cellular uptake to occur and for proper release of the entrapped drug to take place. Students will use prior knowledge of cellular transport and cellular structures to guide them in this inquiry. Once students construct parameters needed to potentially design the nanoparticles, and the teacher has steered them towards working with polymers, they will choose a variable they would like to test on model particles and hypothesize its effect on the particles release of the entrapped material. Students will create their model particles in the lab and then investigate the environmental variable on the particles by designing an experiment in the lab. Students can then draw conclusions on the effectiveness of their particles based on one parameter of their initial design.


Objectives

What should students know as a result of this lesson?

  • The student will comprehend nanoscale measurements
  • The student will identify biocompatibility factors for nanoparticles
  • The students will understand the intra and extra-cellular transport of nanoparticles
  • The student will explain drug release by diffusion and degradation of polymer- environmental factors

What should the students be able to do as a result of this lesson?

  • Students will research and design a potential nanoparticle based on certain parameters
  • Students will hypothesize the effect of environmental factors on the degradation of polymer nanoparticles and the release of encapsulated substance
  • Students will design a controlled experiment testing an environmental factor on the model nanoparticle
  • Students will cite evidence to draw a conclusion on the effect of environmental factors on polymer nanoparticles

Materials

  • Journal article
  • Computers
  • 1% w/v Alginic acid sodium salt from brown algae solution
  • Distilled water
  • Food coloring
  • 0.5% w/v Calcium chloride solution
  • Plastic pipettes
  • 10mL graduated cylinders (1/group)
  • 20mL vials (3/group)
  • Masking tape
  • Petri dish to hold the alginate beads (nanoparticle models)
  • 0.1M HCl to decrease pH between 2-3
  • 0.1M NaOH to increase pH between 12-13
  • pH paper
  • NaCl solutions (1% and 5%w/v)
  • Sodium Citrate solutions (50mM & 100mM)
  • Hotplates or incubator
  • Some type of phosphate solution Ex. Phosphate Buffered Saline
  • Vernier colorimeter
  • Vernier software

Procedures

Engagement

Day 1-1: Questioning for prior knowledge:

  1. What are some ways to deliver medicine/drugs? Ex. Pills, liquid, injection, etc.
  2. What happens once the drug is in your body? Ex. Not specific travels throughout whole body and most medicine never reaches target area before being broken down and/or excreted
  3. What are the downfalls of the systems we have in place for drug delivery? Ex. Have to take over and over to obtain constant results and be at a non-toxic level
  4. How could drug delivery be more effective? Really get them brainstorming on this question, ask question to get them to think about targeting of drugs on cellular or sub-cellular level, controlled time release, toxicity of drug and delivering agent, number of times medication has to be administered

Show students a clip about nanoparticles to get them more focused and interested on the drug delivery with nanoparticles. Possible you tube videos to watch- The first 2 I recommend for the students. Teachers may also want to watch the other 2 to get more information on polymeric nanoparticles and nanotechnology in general.

*Nanoparticle drug delivery in cancer therapy, Yuriy Svidinenko, http://www.youtube.com/watch?v=emEua2eJp1U

*Joanne Crean Nanoparticles in Drug Delivery, TheInnovationAcademy, http://www.youtube.com/watch?v=YvnzgOvFBr4

Polymeric Drug Delivery Systems - Biomaterials - UND Engineering, kookapalooza, http://www.youtube.com/watch?v=b5PhiT0C6h0

Video Journey into Nanotechnology http://nano.cancer.gov/learn/understanding/video_journey.asp

Ask students:

  1. What are the benefits of using nanoparticles?
  2. What would the nanoparticles have to be made out of and why?

Assessment: Through discussing the above questions with students determine that the students have a basic understanding of nanoparticles and drug delivery before starting the Exploration Day 1.

Exploration

Day 1-2: Students will be put into groups and will be exploring some of the following topics: what nanoparticles (NPs) are made of (we will focus on polymer NPs), how NPs work to release the entrapped/encapsulated drug, how NPs interact with the body- extra and intra-cellular transport, degradation of polymer due to environmental factors, byproducts of degradation and toxicity. Teacher will give students a journal article to read to help them research some of the topics above. Article examples:

  1. Muthu M S. Nanoparticles based on PLGA and its co-polymer: An overview. Asian J Pharm 2009;3:266-73
  2. Nitta, S.K.; Numata, K. Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering. Int. J. Mol. Sci. 2013, 14, 1629-1654.

Assessment: Researching Nanoparticles worksheet.

Day 2-2: Teacher will demonstrate the making of the model nanoparticles (alginate beads) and the drug will be represented with food coloring. Then the teacher will show the cell size and scale (http://learn.genetics.utah.edu/content/begin/cells/scale/) so that students are aware of just how small these particles really are. Explain to students that we are using larger particles in order for them to be able to see them. Teacher will also show students proper use of the colorimeter.

Students will then be asked to design an experiment using one of the factors within their smaller groups. They will hypothesize the effect the factor will have on the release of the drug (dye) from the nanoparticle (alginate bead).

Day 3-1: They will run the experiment and collect quantitative data using a colorimeter to measure the absorbance of light at different time points in order to see the diffusion of the dye from the bead. They will then draw a conclusion based on the data they have collected and they will communicate that information to the class. After collecting all the groups' data the class as a whole will have a good idea of the factors that will play a role in the delivery of the drug using that particular NP model.

Assessment: Teacher will walk around to each group when taking measurements to be sure they are using colorimeter properly. Monitor the students' lab work to ensure that safe lab procedures are being followed and that students are following their procedure and are running a controlled experiment. All students are participating in data collection.

Explanation

Day 2-1: Discussion-As a whole class, each group will share the information they learned and have discussions on what parameters need to be met in order to create NPs suitable for biological systems. As a group the teacher will also lead students to making a list of some environmental factors that could play a role in the degradation of the polymer NP and therefore play a part in the release of the drug. Ex. pH, temperature, chelating agents (phosphate, citrate)

Assessment: Check for participation of each group member during the discussion. Each member of the group should have a role (a particular piece of research that they are in charge of)

Day 3-2: Students will complete a lab report for homework which will include the data they have collected and conclusions they have drawn from the data.

Assessment: Students will turn in lab report (Polymeric Nanoparticle Drug Delivery Lab Report) the following day.

Day 4-1: Students will share their results with the class. As a class we will have collected data on multiple variables that could potentially affect the degradation of the NP's (beads) in the body.

Assessment: Check for participation of each group member during the discussion. Each member of the group should have a role (explaining the experimental groups, data that was collected, conclusion they came to based on the data).

Elaboration

Day 4-2: Students would then be able to apply the concepts learned to other types of nanoparticles or drug delivery systems and analyze the effectiveness of those methods based on what they have learned. As a group students should come up with ideas of how this technology could be applied to different diseases or medical problems. Each group will then share one idea with the class.

Assessment: Students should be able to apply what they have learned about nanoparticles to other medical practices.


Prerequisites

Cellular structures and functions

Cellular transport

Scientific method

Designing a controlled experiment


Best Teaching Practices

  • Wait time
  • Questioning
  • Hands on/Mind on learning
  • Real life situations problem solving

Alignment with Standards

NGSS Standards:

  • HS-ETS1-2. Design a solution to a complex real-world problem by breaking it down into smaller, more manageable problems that can be solved through engineering.
  • S-ETS1-3. Evaluate a solution to a complex real-world problem based on prioritized criteria and trade-offs that account for a range of constraints, including cost, safety, reliability, and aesthetics as well as possible social, cultural, and environmental impacts.

Common Core Standards:

  • RST.9-10.3 Follow pecisely a complex multistep procedure when carrying out experiments, taking measurements, or performing technical tasks, attending to special cases or exceptions defined in the text.
  • RST.9-10.5 Analyze the structure of the relationships among concepts in a text, including relationships among key terms (e.g., force, friction, reaction force, energy).
  • WHST.9-10.2 Write informative/expanatory texts, including narration of historical events, scientific procedures/experiments, or technical processes.

Ohio Standards:

  • Identify questions and concepts that guide scientific investigation
  • Design and conduct scientific investigations
  • Formulate and revise explanations and models using logic and evidence (critical thinking)
  • Communicate and support a scientific argument
  • Every cell is covered by a membrane that controls what can enter and leave the cell.
  • Specialized parts for the transport of materials, waste disposal, information feedback

Content Knowledge

Nanoparticles have been increasingly popular as a way to deliver drugs. Nanoparticles can range in size from 10 -1000nm. When nanoparticles are used for drug delivery the drug is enclosed in the nanoparticle at the time of creating the particle. There are many ways to producethe drug encapsulated nanoparticles, such as by dissolving, entrapping and encapsulating the drug into the particle. Creating biodegradable nanoparticles is of great importance so that they will not cause any build up or damage inside the body after use. Scientists have used many different polymers to create nanoparticles that are able to target the site for drug delivery. Using nanoparticles will allow for more precise treatment, use of less of the drug and hopefully less side effects. Polymers that are biodegradable can also be used to control the release of the drug. As the polymer degrades, more and more of the drug will be released into the system, therefore allowing for a continuous, steady amount of drug over an extended period of time. It has also been noted that polymeric nanoparticles also increase drug stability within the body. For all of these reasons stated above polymers have been the ideal choice when using nanoparticles in drug delivery.

Soppimatha K., Aminabhavia T., Kulkarnia A., Rudzinskib W. Biodegradable polymeric nanoparticles as drug delivery devices. Journal of Controlled Release 70 (2001) 1-20.


Safety

  • Goggles
  • Gloves
  • Safety shower and eye wash in case HCl or NaOH contacts skin or eyes

Applications

Nanoscale research is happening in universities all over the world. One application is making nanoparticles (NPs) that have a substance encapsulated or entrapped within it. In this lesson we are concentrating on the use of nanoparticles for drug delivery. The nanoparticles can be created to target specific tissues and then have controlled release of the drug inside through a variety of different variables such as diffusion of the substance and degradation of the NP shell.


Assessment

Engagement questions, Researching nanoparticles worksheet, student participation in nanoparticle discussion, student use of proper techniques and safety in the lab, students participation in the data collection, Polymeric Nanoparticle Drug Delivery Lab Report, Student participation in discussion over results and conclusions of experiment, Each group comes up with an application of nanoparticle technology.

Students should walk away having an idea of the effects of environmental factors of the body on nanoparticle degradation and how this can effect release of encapsulated drug therefore making the drug more or less effective (dependent on the particular situation.)


Other Considerations

Teacher Notes:

Making of alginate beads (model NPs)

Pacing/Suggested Time: The construction of the dropper cars will take the teacher about 20 minutes to complete. The engagement and exploration activities should take about 45 minutes to complete. The graphing and discussion may need an additional 20 minutes.

  1. Create a 1%w/v solution of alginic acid sodium salt in water (1 g/100mL)
  2. Place food coloring into the above solution (amount of food coloring will depend on amount of solution created)
  3. Create a 0.5%w/v solution of Calcium Chloride (1g/100mL)
  4. Use a pipette and drop the alginic acid solution into the calcium chloride solution. Each drop will become a bead (NP). You can adjust the size of the beads based on the size of pipette used. The longer you leave the beads in the CaCl2 solution the more solid they will become. I recommend leaving the beads in for 1-2 minutes.
  5. The teacher can allow students to make their own beads for experimentation or the teacher can have a supply of the beads for the students to use. The beads can be made the day before as long as they are kept in a sealed container.

    Vernier Colorimeter

    For data collection, I had my students test the absorbance of light through their solutions by using a colorimeter. Students should test the solution prior to putting the bead in, in order to get a baseline reading. If absorbance increases that would mean that a greater amount of dye has exited the bead and gone into solution.

    Factors to test, Solutions to prepare ahead of time for student use

    • pH- create an acidic solution, pH 2, using HCl, create a basic solution, pH 12, using NaOH
    • Temperature - you can have vials of distilled water in refrigerator and incubator for students to use.
    • Phosphate Buffer Solution (to represent human body osmolarity and ion concentrations) - you can use tablets to make PBS solution
    • NaCl solutions - 1%w/v and 5%w/v solutions
    • Sodium Citrate solution (to show degradation of NP very quickly)- 50mM and 100mM solutions.

    Overview of experimental design

    Teacher should help guide students in the creation of their lab to think about constants such as amount of solution in vials for each group, time the beads are in the solution (10-15 min is recommended), shake vials 1-3 times before removing bead in order to spread dye throughout solution evenly. Remind students to include a control group.

    Pacing/Suggested Time: This lesson should be taught over a period of about 4 (42 minute) class periods. Students should be introduced to the topic through the engagement section on day 1. Then students should begin the reading and additional research and finish for homework. The next day the class should gather for discussion of what they learned, teacher can demonstrate particle creation and teach students how to use the colorimeter. Then students should develop a controlled experiment testing one variable. The third day should be spent in the lab running the experiments. For homework students will complete their lab reports. On the 4th day students can discuss the conclusion they came to based on their data and then elaborate on other possible uses for nanoparticles in medicine (treatment, prevention, etc.)


    Printable PDF Worksheets