Abstract
BackgroundMalignant pleural effusions are a serious complication of many late stage cancers that adversely affect quality of life. Pleurodesis with talc slurry is a standard treatment option, but clinical failures occur, possible due to poor talc delivery. A novel drug-delivery system was developed that fills the entire thoracic cavity with a liquid foam containing talc. The foam is designed to gel and adhere to the tissue walls at body temperature, to improve talc deposition and efficacy.MethodsRheology, foam stability, and ex-vivo coating and bio-adhesion studies were performed on three concentrations of a novel hydrogel talc foam system that was developed to improve delivery of talc to the pleural surfaces. A New Zealand rabbit model of pleurodesis was used to evaluate effectiveness of the foams at inducing adhesion formation and compared to talc slurry. The rabbits were recovered after they had one of the test agents instilled into their pleura, and then sacrificed after 28 days. Pleurodesis was assessed by a blinded pathologist using a standardized pathological scoring system.ResultsAll talc foam formulations produced foams that gelled at physiological temperatures and were relatively stable for at least two hours. As the concentration of the formulation increased the gelation temperature decreased and the foam adhesiveness increased. Rabbits that received talc foam had significantly greater adhesion formation than talc slurry (mean score of 2.21 vs. 1.18 (p < 0.05)). Rabbits that received the 20% foam developed the most adhesions.ConclusionsThis study demonstrates that our triblock copolymer hydrogel foam delivery system enhances adhesion formation in an experimental model. This novel approach can have important clinical impact, potentially improving efficacy of existing therapies and reducing the need for more invasive treatments.
Highlights
Malignant pleural effusions are a serious complication of many late stage cancers that adversely affect quality of life
One of the simplest and least invasive procedures is bedside talc pleurodesis, Baxter et al Journal of Cardiothoracic Surgery (2020) 15:58 whereby a talc slurry is instilled into the pleural cavity through a chest tube
We investigated using a foam formulation as a drug delivery of talc in a mouse model of malignant pleural effusions
Summary
Malignant pleural effusions are a serious complication of many late stage cancers that adversely affect quality of life. Malignant pleural effusions (MPEs) occur in approximately 200,000 patients in the United States each year, affecting between 7 to 15% of all cancer patients [1]. This abnormal build-up of fluid in the pleural cavity frequently causes progressive shortness of breath and can Current clinical management of a MPE is palliative and involves drainage of the accumulated fluid to relieve discomfort, frequently followed by a procedure termed pleurodesis to induce obliteration of the potential pleural space through inflammation and adhesion formation [2, 3]. Foam is advantageous in increasing both the distribution of talc within the cavity and contact time between talc and tissue
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