Manipulating Drug Release Rates Utilizing Alginate-Based Hydrogels (Group 4)

This week we finished our final testing for one of the hydrogels since the sample was tainted on the way to the lab. We first made the hydrogel by rinsing the mold in a calcium chloride bath. We then filled the mold with alginate infused with vitamin D and sealed the gel with another layer of calcium chloride. We then put the hydrogel in distilled water and left it for an hour to measure the release rate. We then transferred the hydrogel to a second container filled with distilled water. We repeated this process 3 times for a total of 3 samples. We then sent these samples to the lab to see if the release rate of the vitamin D changed every hour and compared the data to the other two hydrogel shapes we tested.

After completing and submitting our final report, we came to lab and discussed what our data should look like and how to detect the dissolution rates from the data we had collected. While we did insert graphs into our rough draft that were based on the data we had received from the instructor earlier in the week from the samples we had given him, we realized that we had plotted the wrong numerical values and created graphs that displayed a better concentration curve than the ones we previously made. We then inserted these graphs into the drafted final report to display a more accurate representation of our results.These graphs can be viewed on our final project page.

This week in lab, we had to turn in the rough draft of our final report so we assigned tasks to each member of the group that corresponded to their areas of expertise and each member finish his or her respective section(s) by Wednesday morning. During this meeting, the group met to finalize the report and double check to see if we needed to add any additional information that was crucial to the project. We also worked together to finish the discussion section so everyone's input could be taken into account and we had a complete and thorough discussion section that full detailed the trials and research processes that led up to our final report. 

This week in class we finalized our project and divided up sections for the project proposal due in class by the end of next week. We also gave the samples we collected during testing this week to the instructor to take to his lab and test using the spectrometer. We also made the alginate with the vitamin D drug more viscous because we hypothesized that the high density of the alginate in the initial testing affected the leaching rate of the drug if not stopped the leaching entirely. We have planned to conduct other tests throughout the week with the new alginate to see if the leaching rate changes from our initial testing to our current testing.

This week outside of class we tested the hydrogels with the drug in them for the leaching rate. We first made the hydrogels by using the molds and creating a calcium chloride coating so the hydrogel would form. We then put the alginate with the drug mixed into it into the mold. Our final step was to put some calcium chloride on the exposed side of the hydrogel to seal the hydrogel shut. We repeated this procedure for each mold and then waited about 10 minutes for the hydrogel to settle in the mold. We then took the hydrogel out using a needle without actually popping the hydrogel and placed it in distilled water. We took samples after every hour but soon saw that the vitamin was not leaching out so changed the time interval to every 12 hours. We also tested a hydrogel that had the vitamin D in the middle of the hydrogel to see if it would leach out the drug differently.

This week outside of class, we restarted our testing process following the new procedure we made in class. We changed the shapes of the molds after our testing from the week before based on which shape worked best for testing and leeched out the vitamin D at a fairly constant rate. We decided that the cylindrical shape worked best.We then created three new molds that had different radii and heights but had the same surface area to see if there was a difference in the rate that the drug leeched out of the hydrogel.

This week during class, we set up the materials we needed for research. We created a stock of alginate that we plan to use for all of the hydrogels to ensure that they all have the same consistency and our results are not skewed due to different concentrations of alginate. We also created a stock of alginate mixed in with vitamin D to ensure that the vitamin D concentration remained constant throughout all of the shapes we tested. We also discussed the changes in our project proposal as well as tried to create a procedure to make the alginate liquid and the alginate with vitamin D by quantifying the amount of alginate to water to vitamin D and tested out different ratios to see which worked best.

Today we finalized the calculations for each 3D printed mold. Each shape will have a total volume of 250 m m³ to ensure that the results are consistent and can be compared across all different shapes. Using these calculations, we created the molds for each shape and started printing them on the 3D printer. We also received feedback from the professor, Dr. Hao Cheng, and changed our initial project proposal from attempting to prolong drug delivery to measuring the degradation of the hydrogel. To reflect this new research goal in our procedure, we added the process of dehydrating and rehydrating the hydrogels to test the rates of degradation. The video below shows the hydrating process from a dehydrated hydrogel.

This week's meeting was spent finalizing the experimental procedure for the experiment. The same procedure will be used to test multiple different hydrogel shapes and drug concentrations. The shapes being tested are square based pyramids, prisms, cones, and cylinders. The concentrations being tested will be 0.2%, 2%, and 20%. In total, there will be 12 different hydrogels being tested. The data collected from these trials will be used to determine the effectiveness of manipulating the ratio between volume to surface area. 

Figure 1: Scientific Method During class today, we started to create research methods for the hydrogels project we will carry out throughout the term. We followed the scientific method and created a plan using the diagram on the left. We have already asked the question which is best communicated in the title of the class: how can we modulate the structure of hydrogels to control its therapeutic release? The first few weeks of the class have been spent doing background research and based on this research, we have constructed the following hypothesis: The ratio of volume to surface area can be changed to prolong drug delivery. Week 3 was spent on experimentation and we have finally reached the stage where we are developing the final procedure for the entire experiment. 

The team met to discuss the shapes, calculations, and material choices for the molds. We previously used PolyLactic Acid (PLA) for our 3D printed molds which had a hard and plastic-like structure but caused the hydrogel to get damaged in the removal process. We then determined that the molds can be 3D printed using Thermoplastic PolyUrethane (TPU), which is a flexible filament that can allow the hydrogel to be easily removed from the mold. 

All materials were brought to class. A 3D printed mold was created to change the shape of the hydrogel. The group began testing and creating hydrogels using 49 grams of water for every 1 gram of calcium chloride while different amounts of sodium alginate were added. Also, calculations were taken in order to determine the volume of the 3D printed mold. The experimentation was successful and helped to learn how the hydrogels work. A cone-shaped hydrogel was created in the 3D printed mold after making circular shaped hydrogels. These are the materials that were brought to class: The 3D printed mold include the white cap and bowl-like shape as shown to the right. The sodium alginate is in the large bag while the calcium chloride is in the white bottle. Pipets and test tubes were also used.

The group came into class and learned about the process of making hydrogels. He further explained the properties of hydrogels and how to manipulate them using different alginate concentrations and calcium chloride concentrations. Two members of the team, Dami and Vriti, helped with the demonstration where they created the hydrogels by dropping the alginate into varied concentrations of calcium chloride solution using a pipet. The remaining time in the class was spent ordering the different supplies we need for the project. The materials acquired are listed below. Materials                 Sodium Alginate (100 g) Calcium Chloride (60 g) 45 mL Test Tube 15 mL Test Tube 3D Printed Alginate Mold Pipette  Food Coloring Newly Printed Alginate Mold

The group went through the proposal to make sure that all of the information is easy to understand and cohesive. The most time consuming process of this meeting was finalizing the design budget and finalizing each section of the Design Proposal. We discussed different hydrogel experimentation techniques such as solubility, pH, hydrogel size and shape, surface area. 

The group brainstormed ideas and finalized the plan for the project proposal. The project proposal was divided into seven separate parts and each member is responsible for creating a rough draft of one or two sections, which need to be completed by Wednesday (4/12). On this day, the team will meet to finalize the project proposal and create a cohesive document to be submitted by the due date (4/14).

During the first class, the group was formed: Brooke Barney, Dami Bolarin, Sam Estrin, Vriti Khurana, and Elizabeth Moroz. Members of the team started to share ideas after a brief presentation from Dr. Hao Cheng, the professor of the class. Dr. Cheng discussed with us the project guidelines, background information, and what experiments he has conducted in the past in his own lab.