Project Proposal

ENGR 103 - Spring 2017

Freshman Engineering Design Lab

“Manipulating Drug Release Rates Utilizing Alginate-Based Hydrogel”

Project Design Proposal

Date Submitted: April 14, 2017

Group Members          Brooke Barney, bab384@drexel.edu

                                     Oluwadamilola Bolarin, odb23@drexel.edu

                                     Samuel Estrin, see54@drexel.edu

                                     Vriti Khurana, vk372@drexel.edu

                                     Elizabeth Moroz, eam422@drexel.edu

Technical Advisor       Dr. Hao Cheng, hao.cheng@drexel.edu

Mohammad Nozari, mn468@drexel.edu

Abstract

“Alginate is a naturally occurring polymer that is finding increasing applications in the biotechnology industry[1].” The purpose of this project is to investigate the properties of alginate-based hydrogels and integrate the hydrogels into a drug delivery system. Specifically, the project focuses on manipulating the ratio of volume to surface area and adjusting the pH of the environment surrounding the hydrogels to prolong drug delivery. With the data collected from the experiments, the main deliverables of the project are 3D molds used to cast the hydrogels into various shapes; the hydrogel itself, that is designed for prolonged drug delivery within the human body; and a blog that documents all technical activities and progress.

1         Introduction

This project was selected from a plethora of ideas revolving around the concept of hydrogels. Utilizing the alginate polymer, the group intends to investigate the formation, absorption, solubility, and dissolution rates of this polymer in order to produce a hydrogel capable of withstanding or even thriving in harsh conditions within the human system.

Several technical challenges will be encountered, ranging from testing of different alginate compounds in solutions of diverse pH and temperatures to 3D printing of large and small scale high resolution molds for hydrogel casting. Factors such as hydrophilicity and hydrophobicity, the affinity for or resistance against dissolution in water or generally polar solutions, similar to those in the human system. Similarly, lipophilicity and lipophobicity, the affinity for or resistance against dissolution in fat or other non-polar solutions, will also be investigated as these properties could be potentially crucial to the group’s system.

A major research focus the group wishes to investigate is the effect the shape (and possibly, the color) of the hydrogel would have on the aforementioned investigations. The team intends to use the volume of the hydrogels as the control, i.e make the volume constants, and manipulate the shapes such that the rates as a function of the surface area can be explored.

The desired outcome of this engineering project is to biochemically engineer a hydrogel that is specially tailored to a specific pseudo-environment within the human system and, possibly, utilize the established hydrogel system for drug delivery.

2         Deliverables

2.1 Hydrogels and Molds

At the conclusion of the project, the team will have produced hydrogels of various shapes with a constant volume and variable surface area. In addition, the 3D printed molds will have been modeled and printed for use in creating the different hydrogel shapes. A larger mold is required for the final presentation. The final deliverable is a hydrogel with a shape that is practical for human consumption and appropriate for prolonged drug delivery.

2.2        CAD Model

The CAD models created will also serve as a visual aid for the final presentation. Either Creo or AutoDesk Fusion 360 will be used in order to create the 3D models to be printed.

2.3        Blog

The blog serves as a chronological record of all activities and tasks completed at each step of the engineering design process.

3         Technical Activities                                                        

3.1       Formation of Alginate Hydrogels

The entire project requires an understanding of the properties of alginate. In addition to reading literature about alginate properties, a lab experiment forming an alginate base would provide familiarity with the production and formation of alginate. The initial investigative task would result in a procedure that is specific to the brand of alginate that is acquired.

3.2       Molds for Alginate Hydrogels

The creation of 3D printed molds is the most feasible option given the project’s time constraint of ten weeks and the goal to minimize the overall cost of the project. Additionally, utilizing plastic molds increases precision and decreases variability during experiential testing.

3.2.1       Mold Creation

Molds specific to the shapes selected by the team are required to cast the hydrogels. This includes using a computer drafting program such as Creo or Fusion 360 to 3D print injection molds.

3.3       Testing

3.3.1       Shape Investigation

After  the completion of technical activities 3.1 and 3.2, the hydrogel substances will be created using the molds of various shapes. The different procedures will be tested to determine the optimal method for generated hydrogels of various shapes.

3.3.2       Dissolution Rates within a System

To determine dissolution rates, hydrogel capsules of each shape will be tested in at least three general pH environments; basic, acidic, and neutral. Depending on the amount of time available, additional testing in specific pH environments may be conducted.

3.3.3       Integration of Alginate Hydrogel with Therapeutic Applications  

Through previously mentioned testing, the group will confirm properties of hydrogels related to the ratio of volume to surface area and dissolution rates with a range of pH environments. Additionally testing of specific drugs is required to determine therapeutic applications of hydrogels cast into various shapes.

3.4       Visual Display

3.4.1       Large Mold Display

The creation of a larger mold of the chosen shape is required for presentation purposes.

3.4.2       Virtual Model

A virtual model of the chosen Alginate structure will be created using Creo or Fusion 360 for integration into the final presentation to aid the general audience’s understanding.

4         Project Timeline

Table 1: Hydrogel Creation Gantt Chart

	Week
Task	1	2	3	4	5	6	7	8	9	10
Investigation, Research, Proposal	X	X	X
Order Materials/Wait For Arrival		X	X	X
Alginate Hydrogel Formation				X	X	X
Hydrogel Experimentation: Shapes, Dissolution Rates				X	X	X	X	X
Use Data From Experimentation to Finalize Hydrogel						X	X	X
Create Final Report and Presentation								X	X	X

5         Facilities and Resources

During the course of the project, the 3D printers located in the Innovation Studio or a 3D printer belonging to a Drexel University student will be used to create plastic molds for the hydrogel. Additionally, the project requires access to a lab space with glassware and general chemistry instrumentation.

6         Expertise

The nature of the group's engineering project results in the need for some expertise. Listed below are the aspects of the project that require expertise and the group members who possess or intend to acquire such skills.

• Conceptual Understanding of Hydrogels & Drug Delivery Systems All Group Members
• 3D Imagery Software & 3D Printing - Sam Estrin
• Project Management & Logistics - Elizabeth Moroz
• Polymer Chemistry & Laboratory Practices - Oluwadamilola Bolarin
• Materials Acquisition & Blog Management- Vriti Khurana
• BioChemical Implementation, Reality Simulation, & 3D Software - Brooke Barney

7         Budget

Materials to be used in this project are shown in the table below.

Table 2: Design Budget

	Category	Projected Cost
1	Sodium Alginate Polymer	$23 for 16 oz
2	Calcium Chloride or Calcium Lactate	$12.94 for 16 oz
3	100 Pipettes	$5.30
4	Food Coloring	$7.99
5	Plastic and 3D-Printed Molds	*
6	Gloves	*
7	pH Sensor	*
8	Glassware	*
	TOTAL	$49.23

* Denotes a material that is owned, borrowed, or created without cost.

7.1       Sodium Alginate Polymer

This polymer will be used in creating the hydrogel for the experiment. Sixteen ounces of Cape Crystal 100% Natural Food Grade Sodium Alginate will be purchased from Amazon.

7.2       Calcium Chloride or Calcium Lactate

Either one of these compounds will be mixed with the polymer in order to create the hydrogel. The chosen compound will be purchased on Amazon.

7.3 100 Pipettes

The pipettes will be used to create the hydrogel and correctly measure the polymer or compound. They will be purchase from Amazon.

7.4       Food Coloring

Food coloring will simulate how color can affect drug delivery and how a medicine works. It will be purchased from a convenience or fabric store.

7.5 Plastic and 3D-Printed Molds

Plastic molds are owned already and a 3D-printed mold will be used to make the hydrogels in.

7.6 Gloves

Gloves will protect the skin of all group members in case of any toxic or hazardous substances.

7.7 pH Sensor

A pH sensor will be borrowed in order to test the hydrogels in different pH to see how they would react to different parts of the body, especially stomach acid.

7.8 Glassware

Glassware will be borrowed in order to mix or measure out substances.

8         References

1. Gombotz, Wayne R., and Siow Fong Wee. "Protein Release From Alginate Matrices." Advanced Drug Delivery Reviews 64 (2012): 194-205. Web. 10 Apr. 2017.
2. Zhang, Shiyi, Andrew M. Bellinger, Dean L. Glettig, Ross Barman, Young-Ah Lucy Lee, Jiahua Zhu, Cody Cleveland, Veronica A. Montgomery, Li Gu, Landon D. Nash, Duncan J. Maitland, Robert Langer, and Giovanni Traverso. "A PH-responsive Supramolecular Polymer Gel as an Enteric Elastomer for Use in Gastric Devices." Nature Materials 14.10 (2015): 1065-071. Web. 11 Apr. 2017.