UNIVERSITY OF TEXAS AT AUSTIN
The objective of this research is to develop nanomanufacturing methods for fabrication of shape-specific ?smart? nanoparticles capable of delivering drugs or imaging agents to targeted tissues in response to disease-specific or physiological signals. Specifically, high throughput, bio-compatible nanoimprint manufacturing processes are developed in this research to fabricate highly monodisperse, enzymatically-triggered nanoscale carriers of drug and imaging agents. The sizes and shapes of the nanoparticles are controlled during the top-down nano-imprint process. Experiments are carried out to evaluate nanoparticle loading, the release of drug and imaging agents, and to characterize the effects of nano-carrier size and shape on carrier transport and cellular uptake in cell cultures and microfluidic environments.This research can transform the manufacturing of nanoparticles for drug and imaging agent delivery as well as address fundamental questions regarding the optimal size and shape of nano-carriers. The obtained nano-carriers can significantly improve therapeutic care of complex diseases such as cancer or cardiovascular diseases. Moreover, the results from this research would not only provide new directions in fabricating drug delivery vehicles with disease-responsive properties, but would also explore the fundamental limitations and practical capabilities of generating three-dimensional, complex structures with nanomanufacturing techniques. If successful, this would eventually lead to the next generation of disease-specific and highly effective therapeutics and also provide novel biomedical applications for nanoimprint lithography. The project is inherently interdisciplinary and involves principles from manufacturing, mechanical, and biomedical engineering. This provides a unique and rewarding educational environment for the students involved including students from underrepresented groups in engineering professions. The results and concepts developed here directly benefit several graduate and undergraduate courses and are disseminated into industry and public by the active participations of the investigators in short courses and seminars for industry and K-12 teachers, students, and parents.
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| AWARD OVERVIEW |
| Award Number |
0900715 |
Funding Agency |
National Science Foundation |
| Total Award Amount |
$900,000 |
Project Location - City |
Austin |
| Award Date |
06/23/2009 |
Project Location - State |
TX |
| Project Status |
More than 50% Completed |
Project Location - Zip |
78758-4445
|
| Jobs Reported |
0.58 |
Congressional District |
10 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
UNIVERSITY OF TEXAS AT AUSTIN |
| Recipient DUNS Number |
170230239
|
| Recipient Address |
101 EAST 27TH STREET STE 4308 |
| Recipient City |
AUSTIN |
| Recipient State |
Texas |
| Recipient Zip |
78712-1500 |
| Recipient Congressional District |
25 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
High Throughput Nanoimprint Manufacturing of Shape-Specific, Stimuli-Responsive Polymeric Nanocarriers for Drug and Imaging Agent Delivery |
| Project Status |
More than 50% Completed |
| Final Project Report Submitted |
No |
| Project Activities Description |
Colleges, Universities, and Professional Schools |
| Quarterly Activities/Project Description |
Our in vitro experiments have yielded shape-dependent particle uptake data in different cells. For disc and rod shaped nanocarriers, nanocarriers with a similar shape but larger volume showed highest uptake in epithelial and immune cells. However, no clear trend was found in endothelial cells. Comparing between disc and rod shaped nanocarriers of a similar volume, discs showed faster and higher uptake than rod shaped nanocarriers in all cell lines. Pharmacological inhibitors of common pathways were used to identify the exact cell uptake mechanism of these nanocarriers. It was found that these particles are primarily uptaken using macropinocytosis and that disc shaped particles are more efficiently uptaken using this process as compared to rods in epithelial cells. It was also found that for disc shaped particles, cells utilize the caveolae mediated uptake pathway while rod shaped particles are excluded from internalization. Multiple uptake pathways (macropinocytosis and clathrin mediated pathway) were found to be responsible for uptake in endothelial cells. In comparison, no unique correlation of shape with uptake pathway utilized was found in epithelial cells. In addition, spheroids, in Vitro tumor models, were established using HEK293 cell lines, for which uptake studies with polystyrene beads show that penetration of 100nm, 200nm and 500nm particles is not significantly different. Total association with spheroids for hydrophobic polystyrene beads was found to correlate with experiments in 2D cultures where 100nm was most uptaken and 500nm was least uptaken. Surprisingly, there was not much difference in uptake between 100nm and 200nm beads. In addition, we have successfully cultured four parallel and confluent HUVEC cell cultures in glass microchannels. These artificial capillaries have been successfully set, stained and imaged using confocal microscopy. The setup will be used to perform dynamic uptake quantification similar to the static uptake study. |
| Jobs Created |
0.58 |
| Description of Jobs Created |
Retained GRAD RES ASST (0.08 FTE) Retained GRAD RES ASST (0.50 FTE) |
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
49-0101 |
| Award Information |
| Award Date |
06/23/2009 |
| Award Number |
0900715 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
49 |
| Funding Agency Name |
National Science Foundation |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
49 |
| Awarding Agency Name |
National Science Foundation |
| Amount of Award |
$900,000 |
| Funds Invoiced/Received |
$848,815 |
| Expenditure Amount |
$851,569 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
611310 |
| Activity Description |
Colleges, Universities, and Professional Schools |
| Sub-Awards Information |
| Sub-awards to Organizations |
0 |
| Sub-award Amounts to Organizations |
$0 |
| Sub-Awards to Individuals |
0 |
| Sub-Award Amounts to Individuals |
$0 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
0 |
| Total Amount of payments to vendors greater than $25,000/award |
$0 |
| Number of payments to vendors less than $25,000/award |
108 |
| Total Amount of payments to vendors less than $25,000/award |
$53,268 |
| Location Information |
| Latitude, Longitude |
30º 23' 7",
-97º 43' 25" |
| Congressional District |
10 |
| Address 1 |
10100 Burnet Road |
| Address 2 |
|
| City |
Austin |
| County |
Travis |
| State |
TX |
| Zip |
78758-4445 |
|
 |