Thursday, December 18, 2025 12/18/2025

Enhanced Delivery of Thrombolytic Carriers for Empyema

Award Number: R01HL152059
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Enhanced Delivery of Thrombolytic Carriers for Empyema - PROJECT SUMMARY Empyema (EMP) is increasing in frequency worldwide and is associated with a mortality rate of up to 20% in patients older than 65 years. Thoracic surgery for treating EMP is invasive and many patients have co-morbidities that preclude its use. Bleeding remains a major concern and occurs in up to about 5-15% of EMP patients treated with intrapleural fibrinolytic therapy (IPFT). These factors offer a premise for the identification of more effective, well-tolerated forms of IPFT that better address the molecular mechanisms governing intrapleural fibrinolysis, particularly in advanced-stage EMP. The need for more efficacious, innovative forms of IPFT represents a gap in the field that is of high priority and addressed in this project. The objective of our study is to identify novel interventions that improve therapeutic outcomes in subjects with EMP using a fibrin-targeted delivery of encapsulated plasminogen activators (PAs) combined with ultrasound sonofibrinolysis (US) in a validated model of Streptococcus pneumoniae induced EMP in rabbits. Liposomal carriers with single chain (sc) tissue (sctPA) and urokinase (scuPA), and resistant to plasminogen activator inhibitor 1 “molecular cage” type complexes with α-macroglobulin (αM/uPA) will be tested. Our preliminary data demonstrate that (i) transthoracic US or sctPA- based liposomes (TELIP) with nanomolar affinity to fibrin improve therapeutic outcomes of an otherwise ineffective dose of fibrinolysin; (ii) US promotes intrapleural formation of αM/uPA, which correlates with success of IPFT in pleural injury. Our hypothesis is that combining intrapleural delivery of low doses of a fibrinolysin encapsulated within fibrin targeted carriers with ultrasound sonofibrinolysis will additively increase the intrapleural half-life of plasminogen activators and rate of fibrinolysis, enhancing the efficacy of IPFT in acute and chronic S. pneumoniae induced EMP. The hypothesis will be tested in three Specific Aims: 1. Determine the minimal effective doses (MEDs) of echogenic liposomal carriers for treatment of S. pneumoniae induced EMP in rabbits. 2. Identify the ultrasound mechanical index and treatment schedule that optimizes outcomes of IPFT in rabbits with S. pneumoniae induced EMP. 3. Use the additivity of transthoracic ultrasound and fibrin- targeted carrier delivery to increase the efficacy of IPFT in S. pneumoniae induced EMP. Our project team consists of two groups with expertise in translational research, IPFT, management of EMP, therapeutic commercialization, and liposomal carrier formulation and delivery. By applying state-of-the-art biochemical, biophysical, physiologic, tissue analysis and imaging techniques, we will accomplish the Research Plan to address the current gaps in empyema treatment and expand our understanding of sonochemical mechanisms. If, as expected, this project succeeds, a new, well-tolerated, more effective and clinically tractable paradigm for IPFT will emerge that may ultimately improve outcomes in patients with empyema.


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 = $0 )
2025	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Lung Diseases Research	000	4	4/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $609,709 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Lung Diseases Research	000	4	8/5/2024	NON-COMPETING CONTINUATION	$609,709
														Subtotal = $609,709

Issue Date FY: 2023 ( Subtotal = $622,151 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Lung Diseases Research	001	3	7/4/2023	NON-COMPETING CONTINUATION	$622,151
2023	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Lung Diseases Research	000	2	10/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $622,151

Issue Date FY: 2022 ( Subtotal = $622,151 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Lung Diseases Research	000	2	8/19/2022	NON-COMPETING CONTINUATION	$622,151
														Subtotal = $622,151

Issue Date FY: 2021 ( Subtotal = $645,651 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Lung Diseases Research	000	1	7/14/2021	NEW	$645,651
														Subtotal = $645,651

Grand Total All Awards = $2,499,662

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Enhanced Delivery of Thrombolytic Carriers for Empyema

Award Number: R01HL152059

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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