TRANSPORT MODELLING USING IN-VITRO AND COMPUTATIONAL APPROACHES FOR BIOPHARMACEUTICAL APPLICATIONS
Date
2025-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Understanding transport within complex, biologically relevant environments is
crucial for advancing the pharmaceutical industry. In-vitro systems serve as vital tools
in this effort, providing controlled platforms for studying and mimicking biological
processes outside of living organisms, such as drug distribution and metabolism. These
experimental setups allow for the isolation and manipulation of variables, enabling
researchers to obtain precise, reproducible, and cost-effective results without the ethical
and logistical challenges of in-vivo testing. As ethical concerns and regulatory standards
grow more stringent, in-vitro methodologies offer a reliable and efficient alternative,
supporting the advancement of therapeutic innovations and the broader goal of
improving human health. Consequently, there is growing interest in developing, and
advancing, in-vitro research platforms to more accurately replicate complex biological
systems to aid with drug development.
This thesis contributes to that effort by addressing two complementary aspects
of in-vitro drug delivery research: (1) the simulation of an advanced Tangential Flow
Filtration (TFF) device for gene therapy applications, and (2) the creation of an
experimental platform to study aerosol deposition in pediatric airways for inhalable
therapeutics.
The first section focuses on a new and improved version of a widely used TFF
device, modified by Bomb et al.,
1 which is simulated using COMSOL Multiphysics to
analyze internal concentration and velocity profiles. Unlike traditional TFF systems,
this updated model provides an increased interaction between cells and therapeutic
components within the device. Understanding the transport phenomena within this
system is particularly relevant to applications such as T-cell transduction, a key process
in the development of cell-based immunotherapies. The simulation platform developed
offers a cost-effective and flexible means to explore experimental conditions in silico,
reducing the need for iterative experimental testing.
The second part of the work introduces an experimental in-vitro framework for
investigating the influence of tonsil size on aerosol deposition in pediatric upper
airways. Anatomically accurate, 3D-printed, models were used to simulate deposition
patterns across varying degrees of tonsilitis. Initially, three distinct patient-based airway
models with varying tonsil sizes were tested to evaluate the effects of different degrees
of tonsil size on aerosol behavior. To eliminate the influence of inter-patient variability,
and more precisely isolate the effect of tonsil size, the experiments were subsequently
re-run using a single airway geometry in which the tonsils were artificially enlarged.
Ultimately, this system provides an in-vitro framework for studying how airway
anatomy influences drug delivery in pediatric patients, without the need for in-vivo
experimentation. Contributing to the development of more effective, and targeted
aerosol-based therapies through a deeper understanding of transport phenomena.