The biopharmaceutics group has a long tradition of investigating and identifying factors governing oral absorption. Over the last 30 years a variety of different pre-clinical and clinical models have been established, refined and used. These models range from transport assays in cell monolayers to in situ human intestinal perfusions, using the revolutionary Loc-I-Gut technique. All absorption studies are supported by the group’s well-developed analytical facilities, which includes UPLC-UV and UPLC-MS-MS, and coupled with extensive pharmacokinetic assessments and biopharmaceutical modelling.
The research is currently focused on understanding the mechanisms behind the absorption of nanoformulations and poorly permeating drug compounds, and how to exploit their perceived weaknesses in order to increase the bioavailability, creating better medicines – now and in the future.
Our research aim is to improve the treatment for the most common type (80-90%) of liver cancer, also known as hepatocellular carcinoma or HCC. We started back in 2011 by evaluating the current treatment options for intermediate stage HCC using in-vitro and in-vivo studies as well as a clinical trial.
Since 2017 we are working on developing new innovative formulations to improve treatment outcome and reduce side effects.
Background - TACE
Transarterial chemoembolization (TACE) is one of the most common treatments for intermediate stage HCC. This treatment is usually given as either an emulsion or microparticle formulation that is administered intra-arterially to the tumor in the liver (see figure). Both formulations are loaded with the cytotoxic drug doxorubicin (DOX). The artery in question supplies the tumor and the rest of the liver with oxygen-rich blood and both of these formulations aim to block smaller blood vessels to create an embolized (oxygen-poor) environment. When they are in place, DOX is released to kill the tumor cells.
Although this sounds smart in theory, research has shown that TACE treatment only prolongs life for a few months and can therefore be considered as only a palliative treatment method for HCC patients.
Evaluation of clinical formulations
Since 2011, we have been working with evaluating these two clinically relevant formulations that are regularly used to treat HCC patients. We have developed several in vitro methods for studying drug release at the detail level and have used mathematical models to explain differences and similarities. Several in vivo studies including a clinical study have helped us to correlate and model our in-vitro and in-vivo data to gain a better understanding of how the emulsion and microparticles behave in the body. Read more in our list of publications!
Since 2017, we are working on developing new innovative micro- and nano-formulations to improve HCC treatment. We have nanoparticles as the focus area and in the picture below you can see an illustration of a nanometer sized particle loaded with DOX and equipped to both avoid clearance by the body’s immune system and to target for the right cells (tumor in the liver).
Illustration by Fredrik Kullenberg
Fundamental parameters governing the absorption of inhaled drugs
The lungs are in many ways optimal as a route of drug delivery for both local and systemic treatment of various diseases. However, there is a need in the pharmaceutical development for improved understanding of parameters involved in the absorption and local disposition of inhaled drugs, to enable better predictions of lung residence-time, dosage regimen and/or optimization of formulation.
Figure 1. Overview of the mechanisms involved in pulmonary drug absorption; drug dissolution, permeation, tissue retention and clearance. (Illustration by Johanna Eriksson)
The overall objective of this project is to improve mechanistic understanding of pulmonary drug delivery and absorption from the lung. This will be obtained by developing and evaluating in vitro, ex vivo and in silico models, with focus on dissolution, epithelial permeability and tissue retention.
Novel mechanistic biopharmaceutical models and new knowledge that will be important for the successful pharmaceutical and clinical development of pulmonary drug products.
This project is part of the Swedish Drug Delivery Forum
Contact Johanna for more details!