Synthesis of an Electromagnetically-Controlled Corn-Starch/PVA Biopolymer Microcube for Extended and Targeted Drug Delivery

Scientists have recently focused on water-soluble polymer thin film matrices with integrated protein or starch bases to increase mechanical characteristics of extended-release drug delivery devices. Unfortunately, a biocompatible, dissolvable micro-carrier that can be maneuvered throughout the body has rarely been researched despite its potential for extended-release and targeted drug delivery. This research proposes the novel synthesis of a water-soluble cornstarch/PVA biopolymer matrix embedded with microclusters of iron colloidal spheres for subcutaneous maneuverability via external electromagnetic fields. Biopolymer films were synthesized with a 2:3 ratio of PVA (Mw-100,000) to cornstarch, using modified methods from Othman et. al. Fe3O4 magnetic nanoparticles (NP's) were prepared by co-precipitation of ferric and ferrous ions in an aqueous ammonia solution under N2-atmosphere. Resultant NP's were then coated with PVA to ensure homogeneous mixing of colloidal spheres with the biopolymer, which was molded using a printed three-dimensional template. Coating of the biopolymer matrices were supported by FTIR/SEM analyses. Anticancer chemotherapy drug, doxorubicin hydrochloride (DOX), was loaded onto the PVA/Fe3O4 NP's. DOX loading, and subsequent release into aqueous medium (to mimic drug delivery), was quantified using the drug's native fluorescence at 553/590nm, with a 230nm excitation. 1.2µg DOX/mg PVA/Fe3O4 loading was achieved in as little as 5days, with as much as 75% release of the drug in only 50hours, into slightly acidic aqueous medium at 37oC. 100mm3 cornstarch/PVA films with embedded DOX/PVA/Fe3O4 colloidal-NP's were constructed, and found to be magnetically motorized and water soluble over 7hours, for release of the DOX load in ~2days from mimicked tumor-site localization.


I live in Greenwich, CT, and attend Greenwich High School, a self-described bubble barricaded off from the rest of the world. Because of this, I must exert additional effort to acquire a globally aware perspective, and the desire to provide others with the opportunities I was given fuels many of my interests. For example, I started a program to help middle schoolers engage in STEM by conducting their own research with the help of high school volunteers. I also started a program to foster an early love for science in elementary school students, in which I teach basic scientific concepts through interactive lessons and fun experiments. I was originally interested in science by my middle school's science research class, and have since tried to provide children with the same positive exposure to STEM that I received. In addition to teaching, I love nature and spend my free time hiking and playing tennis. 

The scientist I most admire is Marie Curie, who, as a female chemist, has inspired me to overcome the traditional gender inequalities that can be found in STEM. I plan to continue with chemistry and engineering after college, hopefully becoming a research scientist in academia. The chance to compete in the Google Science Fair is a way for me to connect to a similar community of research scientists who are my age, in a manner that allows us to exchange ideas and build off of each other. Winning would fuel my ambition to help people through science research. 


This research proposes the novel synthesis of a dissolvable and biocompatible corn-starch/PVA micro-carrier that is hydrotropic and easily maneuverable with electromagnetic fields or other external stimuli. This device would potentially be able to deliver drugs to targeted parts of the body and rival other current drug delivery options. It is hypothesized that a corn-starch/PVA microcube will successfully delivery water-insoluble drug molecules from one point to another with electromagnetic fields as an external stimulus, and that after targeted distribution of the drug, the polymer film will completely dissolve. This is hypothesized due to the hydrotropic properties of cornstarch and water-soluble properties of PVA, as well as their miscibility with each other.


In recent years, extended-release drug delivery platforms, such as oral films, injections, or implantable formulations have received heightened attention for the purpose of decreasing the frequency of drug dosages. Specifically, many scientists have focused on thin polymer films to accomplish coating of proteins or drugs in a diffusion-mediated extended-release drug delivery system. A water-soluble and biocompatible polymer thin-film matrix would potentially be able to release small drug dosages as it dissolves. For these reasons, dissolvable polymer-blend film configurations have become increasingly important for convenient extended drug delivery. Of similar interest is the integration of protein or starch bases into the thin-film matrices to increase mechanical characteristics of the drug delivery devices. The mixing of various biopolymers, such as wheat, collagen hydrolysate, and gelatin with water-soluble synthetic polymers such as polyvinyl alcohol (PVA) could potentially lead to a biocompatible and water-soluble drug-distribution system. Previous research suggests that corn starch in particular would act as a successful biopolymer with PVA, increasing the miscibility of the thin film. Due to the hydrotropic nature of cornstarch, it has the potential to make water-insoluble drug molecules soluble within a drug-transportation structure.

In previous studies, researchers have embedded metallic clusters of iron nanoparticles in 3-dimensional or thin-film structures to navigate carriers with weak electromagnetic fields. In this research, iron colloidal spheres and drug molecules will be embedded in a corn-starch/PVA soluble biopolymer microcube to yield a novel, biocompatible microdevice for extended-release and targeted drug delivery. This microstructure could be used for a variety of applications, such as targeting tumors with macromolecular or water-insoluble drugs.


4 g of PVA with a molecular weight of 100,000 and 6 g of practical grade cornstarch were added to 110 mL of di-water. The resulting precursor solution was stirred with a magnetic stir bar and simultaneously heated at 85°C for 1 h. Various plasticizers were then added to the precursor. ~1.5 g glycerol, ~0.6 g Tweenum-80, and ~1.2 g paraffin wax were added while the solution was continuously stirred for another 10 min. The paraffin wax was melted beforehand. The resulting polymer was poured onto glass plates. The precursor had a less-viscous consistency compared to trials 1 and 2, mostly due to the absence of hexamethylenetetramine in the polymer solution and the lower molecular weight of the PVA. Due to its liquid consistency, the glass plates were oven dried for 6 h at 95°C, as opposed to 1 h, the drying time for previous trials and literature. After oven drying, samples were peeled off from glass plates with a spatula. 

1. Partially dissolved film under SEM

For movement via electromagnetic fields, PVA-coated Fe3O4 colloidal nanoparticles (NP’s) were suspended in the corn-starch/PVA structure. PVA coating ensures that the resulting solution is homogenous. 

First, a mixed solution of Fe2+ and Fe3+ ions with a molar ratio of 1:2 was prepared by dissolving ~1.06 g of FeCl2*4H2O and ~3.91 g of FeCl3*6H2O in 30 mL of di-water. The resultant precursor was then stirred in a 100 mL beaker on a stirring plate for 20 min. under nitrogen. Then, 3 mL of 28% ammonium hydroxide was shot into the filtrate and stirring speed was increased to uniformly precipitate nanoparticles. The precipitate was then stirred for 12 h to evaporate excess ammonia. Iron nanoclusters were resuspended in 25 mL of di-water after three washes with distilled water. For coating of the magnetic iron oxide nanoclusters, a 4% PVA solution was prepared using a mixture of dry PVA powder dissolved in di-water at 60°C. The iron oxide nanoparticles were added to and mixed with the PVA solution using a magnetic stirrer for 12 h. Coated nanoclusters were then separated with a pipette into a 100 mL beaker and characterized with SEM analyses.

Anticancer chemotherapy drug, doxorubicin hydrochloride (DOX), was loaded onto the PVA/Fe3O4 NP’s. DOX loading, and subsequent release into aqueous medium (to mimic drug delivery), was quantified with FL Spectroscopy using the aromatic drug molecule’s native fluorescence at 590 nm, with a 390 nm excitation. Release studies were conducted in a slightly acidic aqueous medium at 37°C to synthesize the acidic extracellular microenvironment of tumor tissues. To determine the concentration of DOX adsorbed and released by colloidal NP’s, a calibration of concentration versus fluorescence intensity at 590 nm was prepared based on serial dilutions of a 0.5 mg/mL DOX standard in di-water. 

After successful synthesis of corn-starch/PVA biopolymer films and PVA/Fe3O4 colloidal NP’s, as well as subsequent drug studies with DOX, three-dimensional structures were formed via a 3D-printed template. ~100mm3 cubes were formed after colloidal spheres and the biopolymer solution were mixed.



For drug adsorption studies, 60 mg PVA/Fe3O4 colloidal NP’s were submerged in a 0.5 mg/mL DOX solution in di-water. The decreasing DOX concentration in solution was monitored for 5 days by separating colloidal spheres and reading the resultant mixture. It was found that after 5 days, concentrations of 7.8 µg/mL were present, and 7.2  µg successfully coated PVA/Fe3O4 NP’s. For release studies, DOX-coated PVA/Fe3O4 NP’s were manually separated with a magnet and placed in 2 mL of di-water. After 50h, the rate of release dropped off significantly, with a final release of 26.89 µg from the NP’s into the solution, ~70% of original DOX load. 

Fig 1. FL Spectroscopy emission spectra of DOX standard solution with 60 mg of Fe3O4 NP's. Excitation wavelength= 390 nm, with excitation and emission slits at 6 and 8.5 nm, respectively. Each spectrum is at one day apart. Initial reading is at 1000.3.

Fig 2. Graph of DOX adsorption onto NP's as a function of time (days). Lowering concentrations in the original solution were plotted using collected calibration standards. DOX loading peaked in ~5 days.

Fig 3. Graph of DOX release from NP's as a function of time (hours). The majority of DOX was released after ~20 hours, and complete DOX release was achieved in ~50 days. This means that up to 20 hours of concentrated drug release can be achieved from the PVA-coated NP's alone, before added to the matrix. The overall drug capacity of the device is thus increased.

Dissolution studies with FTIR analysis showed that the corrected dissolution areas of polymer samples as a function of time increased logistically. The majority of the polymer dissolved after 2h, after which the rate of dissolution decreased. Total dissolution of the polymer in water took ~7h, meaning DOX loaded onto the polymer would disperse for ~7h. This time, plus the possible drug release from the PVA-coated iron NP's, means concentrated drugs could continuously release from the delivery device for up to 1 day.

Fig 4. FTIR spectra of the cornstarch/PVA biopolymer dissolved in di-water for periods of 0.5h, 1h, 1.5h, 2h, and 7h.

Fig 5. Graph of corrected dissolution areas of the biopolymer cubes as a function of time (hours). 

Studies of the magnetization of both uncoated and coated NP’s were performed using a Lake Shore MicroMag vibrating sample magnetometer (VSM). Measured magnetic moment values were mass normalized for purposes of inter-sample comparison. Hysteresis M(H) loops were recorded at ambient temperature and applied to magnetic fields of ± 5 kOe (0.5T) in 2.5 Oe steps. The mass magnetization was calculated by dividing the measured magnetic moment m (emu) by the sample mass in grams. Both NP's were superparamagnetic, and PVA-coating reduced mass magnetization by only 38%, suggesting that the PVA-coated NP's are still highly responsive to external magnetic fields for mobility.

Fig 7. Hysteresis M(H) loop of uncoated NP's with a mass magnetization of 47.8 emu/g.

Fig 8. Hysteresis M(H) loop of coated NP's with a mass magnetization of 29.7 emu/g, a 38% reduction.


In this research, a corn-starch/PVA biopolymer matrix was successfully synthesized, and magnetic carriers consisting of PVA-coated iron oxide colloidal nanoclusters were achieved through the co-precipitation of ferric and ferrous ions in the presence of ammonia solution. After embedding of the magnetic carriers in the biopolymer, three-dimensional structures were formed from a 3D-printed mold and characterized with SEM/FTIR analyses, which showed total dissolution of the matrix after 7h. Anticancer chemotherapy drug, doxorubicin hydrochloride (DOX), was loaded onto the PVA/Fe3O4 NP's. DOX loading, and subsequent release profiles into aqueous medium (to mimic drug delivery), were quantified using the drug's native fluorescence at 553/590nm, with a 230nm excitation. 1.2µg DOX/mg PVA/Fe3O4 loading, the saturation value, was achieved in as little as 5 days, with as much as 70% release of the drug in only 50 hours, into slightly acidic aqueous medium at 37oC. 100mm3 cornstarch/PVA cubes with embedded DOX/PVA/Fe3O4 colloidal-NP's were constructed, and found to be magnetically motorized and water soluble over 7hours, for release of the DOX load in ~2days from mimicked tumor-site localization.

The novel DOX/PVA/Fe3O4 NP’s embedded in a corn-starch/PVA 3D cube matrix allows for targeted and extended-release drug delivery, as well as increased drug storage. Water-insoluble drugs are capable of being loaded onto the magnetic carrier and the biopolymer, increasing drug capacity. Additionally, the hydrotropic properties of corn-starch allow for insoluble drugs to be released over an extended period of time, as demonstrated by the release program of DOX. The non-invasive drug delivery device was found to be magnetically motorized and can be externally controlled with electromagnetic fields due to the magnetic properties of Fe3O4 NP’s. The dissolution time of the polymer as well as release time allow for extended drug delivery to limit the inconvenience of prolonged treatment. The novel, magnetically motorized drug carrier is thus able to deliver drugs to localized subcutaneous areas and is more effective than other delivery devices, as well as biocompatible.

Future research would investigate the synthesize of microstructures from PVA/Fe3O4 matrices via economically efficient and simple methods for feasible subcutaneous movement. The macro scale drug delivery system will be reduced through polymer molding, in which a rigid master will be prepared by lithography techniques. This process allows for the replications of microstructures, allowing for a large-scale application of the novel magnetic carrier.



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My research teacher, Mr. Andrew Bramante, played a crucial role in this project. Mr. Bramante taught how to use FL Spectroscopy and FTIR Spectroscopy at my high school, so that I could collect data. He also provided me access to the Lakeshore VSM (Vibrating Sample Magnetometer) for magnetism studies. 

I would also like to acknowledge Mount Sinai Medical Center, for providing me use of their facilities, specifically the Scanning Electron Microscope.