Macroaggregated albumin particles as intravenous drug formulation for lung delivery
department or school: Pharmaceutical Sciences, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Bergamo, Marta
issued: 2025-04-30T07:00:00Z
issued: 2024
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Macroaggregated albumin microparticles (MAA) are particles routinely used in the clinic as imaging agents for the diagnosis of pulmonary embolism (PE) due to their ability to passively target the lungs. Since albumin is biocompatible and biodegradable, MAA represents an attractive carrier for the delivery of drugs to the lungs. Particularly, there is still a great need for lung targeting delivery systems of fibrinolysis-enhancing drugs for the treatment of PE. While these drugs are effective in resolving blood clots entrapped in the pulmonary vasculature, they are administered intravenously resulting in severe side effects limiting their clinical use. Therefore, it is critical to develop formulations for their targeted delivery to reduce systemic exposure, thus improving their safety profile. The aim of this project was to formulate the anticoagulant tiplaxtinin with albumin microparticles for delivery to the lungs. MAA loaded with tiplaxtinin (MATi particles) were prepared by one-pot synthesis of the drug with bovine serum albumin (BSA) at controlled conditions. Particles were characterized for their size, drug loading, stability, and cytotoxicity. Acute toxicity of the particles was investigated in vivo by intravenous administration of MATi particles prepared with radiolabeled BSA (¹¹¹In-MATi) to healthy mice. Dual radiolabeling of the MATi particles was obtained by labeling tiplaxtinin with an additional radioisotope (³H). This allowed us to investigate the biodistribution of the albumin particles and the drug simultaneously and compare it to the unformulated tiplaxtinin following intravenous administration into healthy mice. MATi particles had a size distribution comparable to clinically used MAA, averaged a drug loading of 26%, showed good stability, and signs of toxicity observed were affected by the drug itself. In vivo, 60% of injected dose accumulated in the lungs upon injection and showed no overt signs of toxicity. When delivered with the particles, up to…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/88067
note: MACROAGGREGATED ALBUMIN PARTICLES AS INTRAVENOUS DRUG FORMULATION FOR LUNG DELIVERY by Marta Bergamo M.Sc., The University of Copenhagen, 2018 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pharmaceutical Sciences) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2024 © Marta Bergamo, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Macroaggregated albumin particles as intravenous drug formulation for lung delivery submitted by Marta Bergamo in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Pharmaceutical Sciences Examining Committee: Prof. Urs Häfeli, Faculty of Pharmaceutical Sciences, UBC Supervisor Prof. Marcel Bally, Faculty of Medicine, UBCch University Examiner Prof. Charles Haynes, Michael Smith Laboratories, UBC University Examiner Prof. Marianna Foldvari, School of Pharmacy, University of Waterloo External Examiner Additional Supervisory Committee Members: Prof. Abby Collier, Faculty of Pharmaceutical Sciences, UBC Supervisory Committee Member Prof. Hanne Mørck Nielsen, Department of Pharmacy, University of Copenhagen Supervisory Committee Member Prof. Christian Kastrup, Michael Smith Laboratories, UBC Supervisory Committee Member iii Abstract Macroaggregated albumin microparticles (MAA) are particles routinely used in the clinic as imaging agents for the diagnosis of pulmonary embolism (PE) due to their ability to passively target the lungs. Since albumin is biocompatible and biodegradable, MAA represents an attractive carrier for the delivery of drugs to the lungs. Particularly, there is still a great need for lung targeting delivery systems of fibrinolysis-enhancing drugs for the treatment of PE. While these drugs are effective in resolving blood clots entrapped in the pulmonary vasculature,…
has type: Thesis/Dissertation
date issued: 2024-05
is shown at: 10.14288/1.0441995
language: eng
degree discipline: Pharmaceutical Sciences
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Häfeli, Urs
type: Text
identifier URI: http://hdl.handle.net/2429/88067