DRUG DELIVERY SYSTEM AND TARGET-ASSOCIATED CYTOSTATIC FORMULATION
Dr. Patrick Zardo
Development of an innovative drug delivery system and a target-associated cytostatic formulation for the clinical establishment of intrathoracic chemoaerosol therapy as a new treatment method for thorax-associated malignancies
The aim of the project is the development and testing of suitable methods for the safe application of intrathoracic chemoaerosol therapy in the preclinical model as well as the technical establishment for later clinical use. The focus here is both on a user-friendly, cost-conscious design and on employee safety during implementation.
Together with our cooperation partner, Pharma Resources GmbH, the medical technology components for the application of intrathoracic chemoaerosol therapy are being developed and evaluated for later clinical use. In addition, an optimal cytostatic formulation for intrathoracic chemoaerosol therapy is being evaluated to match the components. Pharma Resources GmbH is coordinating the product development side of the project.
The project is funded by the European Union via the Regional Development Fund (ERDF) and by the state of Lower Saxony.
Background:
The development project is generally based on the clinical fact that in progressive, primarily malignant diseases of the pleura such as mesothelioma, tumors growing into the pleura such as thymoma or secondary metastasis of a malignant underlying disease into the pleura, often no or hardly satisfactory tumor control can be achieved by standard systemic chemotherapy or surgical intervention: The malignant disease recurs early, shows no response or even progression under conventional chemotherapeutic therapy. Malignant mesothelioma of the pleura (pleura of the ribs and lungs) and advanced thymus carcinomas have an extremely poor prognosis in terms of cure and long-term survival rates, and the range of available therapeutic options is limited. One of the more novel treatment approaches for pleural mesothelioma, pleural carcinomatosis and thymic carcinoma is the HITHOC procedure(HyperthermicIntra-ThOracal Chemotherapy), which involves a surgical procedure: a previously extensive, macroscopic tumor removal under anesthesia is followed by the chemotherapeutic, microscopic destruction of any remaining local tumor tissue under irrigation with a heated chemotherapy solution. Although this treatment concept is gaining more and more attention in thoracic surgery, the procedure is extremely complex from a technical and surgical point of view and is not suitable for every patient. In addition, the amount of cytostatic drugs used in this procedure is comparatively higher than would be the case with the chemoaerosol therapy to be developed.
1.
Wronski S, Beinke S, Obernolte H, Belyaev NN, Saunders KA, Lennon MG, Schaudien D, Braubach P, Jonigk D, Warnecke G, Zardo P, Fieguth HG, Wilkens L, Braun A, Hessel EM, Sewald K; U-BIOPRED Study Group. Rhinovirus-induced Human Lung Tissue Responses Mimic COPD and Asthma Gene Signatures. Am J Respir Cell Mol Biol. 2021 Jun 28. doi: 10.1165/rcmb.2020-0337OC. Epub ahead of print. PMID: 34181859.
2.
Zhong S, Golpon H, Zardo P, Borlak J. miRNAs in lung cancer. A systematic review identifies predictive and prognostic miRNA candidates for precision medicine in lung cancer. Transl Res. 2021 Apr;230:164-196. doi: 10.1016/j.trsl.2020.11.012. Epub 2020 Nov 28. PMID: 33253979.
3.
Renne J, Gutberlet M, Voskrebenzev A, Kern A, Kaireit T, Hinrichs J, Zardo P, Warnecke G, Krüger M, Braubach P, Jonigk D, Haverich A, Wacker F, Vogel-Claussen J, Zinne N. Multiparametric MRI for organ quality assessment in a porcine ex-vivo lung perfusion system. PLoS One. 2018 Dec 27;13(12):e0209103. doi: 10.1371/journal.pone.0209103. PMID: 30589907; PMCID: PMC6307703.
4.
Renne J, Gutberlet M, Voskrebenzev A, Kern A, Kaireit T, Hinrichs JB, Braubach P, Falk CS, Höffler K, Warnecke G, Zardo P, Haverich A, Wacker F, Vogel-Claussen J, Zinne N. Functional Pulmonary Magnetic Resonance Imaging for Detection of Ischemic Injury in a Porcine Ex-Vivo Lung Perfusion System Prior to Transplantation. Acad Radiol. 2019 Feb;26(2):170-178. doi: 10.1016/j.acra.2018.05.006. Epub 2018 Jun 19. PMID: 29929935.
5.
Neuhaus V, Danov O, Konzok S, Obernolte H, Dehmel S, Braubach P, Jonigk D, Fieguth HG, Zardo P, Warnecke G, Martin C, Braun A, Sewald K. Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices. J Vis Exp. 2018 May 9;(135):57042. doi: 10.3791/57042. PMID: 29806827; PMCID: PMC6101160.
6.
Starke H, Zinne N, Leffler A, Zardo P, Karsten J. Developing a minimally-invasive anaesthesiological approach to non-intubated uniportal video-assisted thoracoscopic surgery in minor and major thoracic surgery. J Thorac Dis. 2020;12: 7202-7217. doi:10.21037/jtd-20-2122
Working Group Drug Delivery System and Target-Associated Cytostatic Formulation
Nicole Ernst
Phone: +49 (0) 511 - 532 34399
Mail: ernst.nicole@mh-hannover.de