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Local dual delivery of a chemotherapy and an anti-angiogenic agent from an injectable functionalized biodegradable biomaterial system for the treatment of gliomas

Award Number: SC3GM135138
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/16/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Local dual delivery of a chemotherapy and an anti-angiogenic agent from an injectable functionalized biodegradable biomaterial system for the treatment of gliomas - PROJECT SUMMARY/ABSTRACT Each year, around 10,000 patients in the US are diagnosed with gliobastoma multiforme (GBM), which is the most common, aggressive and high-grade form of these brain tumors (82% of malignant gliomas). Currently, the median survival for this disease is around 21 months after diagnosis. Despite advances in the different methods of therapy (i.e. radiotherapy, immunotherapy and chemotherapy), the prognosis for gliomas has not been dramatically improved through the years. For tumors located in the brain, systemic delivery of agents has to overcome many obstacles for the successful delivery of the drug to the site including the critical step of having to cross the blood brain barrier (BBB). Due to the difficulty and high cost related to developing new therapeutics, focus should be placed on optimizing available drugs by ways such as delivering them locally using biomaterials. Local delivery of an anti-angiogenic factor (i.e. minocycline) and systemic delivery of a chemotherapy agent (i.e. bis-chloroethylnitrosourea (BCNU) or temozolomide (TMZ)) has been shown to improve median survival compared to the delivery of the systemic delivery of the chemotherapy agent alone in a rodent glioma model. Thus far, a lot of studies have been performed to study the delivery of both of these factors systemically or one factor systemically and the other factor locally to treat gliomas. However, the local deliver of both of these agents by combining both of them in an implantable device has not been investigated. It is hypothesized that the local delivery of both a chemotherapy agent that will impede the growth of cancer cells and an anti-angiogenic factor that will block blood vessel formation can better inhibit cancer progression compared to the delivery of these drugs systemically or locally alone. An ideal therapy should target tumor cells and avoid damaging non-tumor cells which can result in memory impairment, decline in brain function and low quality of life. CD44 and CD105 have been shown to be highly expressed on human glioma cell lines and endothelial cells, respectively and thus we further hypothesized that biomaterials functionalized with antibody against these markers can decrease non-targeted toxicity and increase bioactivity on targeted cells. The overall goal of this proposal is to develop a biodegradable composite system that has the ability to sustain the release of a chemotherapy and an anti-angiogenic agent and target cells of interest for glioma which may also be applied to other tumor types. The results from this work will contribute to the development of more effective therapies for the treatment of brain gliomas.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$453 )
2025	2023	THE UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	4	8/28/2025	NON-COMPETING CONTINUATION	-$453
														Subtotal = -$453

Issue Date FY: 2023 ( Subtotal = $108,975 )
2023	2023	UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	4	3/1/2023	NON-COMPETING CONTINUATION	$108,975
														Subtotal = $108,975

Issue Date FY: 2022 ( Subtotal = $108,975 )
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	001	3	6/20/2022	NON-COMPETING CONTINUATION	$10,898
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	3	2/7/2022	NON-COMPETING CONTINUATION	$98,077
														Subtotal = $108,975

Issue Date FY: 2021 ( Subtotal = $108,975 )
2021	2021	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	2	2/24/2021	NON-COMPETING CONTINUATION	$108,975
														Subtotal = $108,975

Issue Date FY: 2020 ( Subtotal = $108,975 )
2020	2020	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	1	3/16/2020	NEW	$108,975
														Subtotal = $108,975

Grand Total All Awards = $435,447

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Local dual delivery of a chemotherapy and an anti-angiogenic agent from an injectable functionalized biodegradable biomaterial system for the treatment of gliomas

Award Number: SC3GM135138

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/16/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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