Parenteral Drug Delivery Projects

Physiochemical Aspects of Subcutaneous Administration of Drugs

Marcus Wanselius portrait photoResearch scientist: Marcus Wanselius, MSc
Principal investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Subcutaneous administration of drug formulations is an attractive alternative for the growing amount of active pharmaceutical ingredients (APIs) with low oral bioavailability. Therefore, it is important to investigate and understand the interactions between different drug formulations and the subcutaneous adipose tissue (hypodermis).

Marcus Wanselius research

Aim. The aim of the project is to provide a mechanistic understanding of how APIs (especially biologics) and excipients in drug formulations interact with the components of the extracellular matrix in the hypodermis.A Further aim is to develop new formulation principles resulting in sustained release and high bioavailability of the APIs.

Out-come. The investigation will provide a basis for the development of novel in vitro methods to model the behaviour of subcutaneously administrated pharmaceutical products.

Amphiphilic Properties of Drug Molecules and Their Self-Assembly in Presence of Phospholipids

Vahid Forooqi Motlaq portrait photoResearch scientist: Vahid Forooqi Motlaq, MSc
Principal Investigator: Associate Professor Magnus Bergström, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Molecular components such as phospholipids, surfactants, proteins and drug molecules consist of both hydrophilic and lipophilic parts and are involved in various drug delivery systems. As a result, these components are able to self-assemble and interact strongly with one another in ways that usually determine molecular release mechanisms in drug delivery systems.

Vahid research

Aim. The aim of the project is to study the interactions and self-assembly in mixtures of different amphiphilic drug molecules and phospholipid bilayers. The study includes locating the drug molecules near liposomes and other bilayer structures, as well as to investigate their impact on bilayer structure, by mainly using various small-angle scattering techniques.

Outcome. A better fundamental understanding of self-assembly structures and release mechanisms in drug delivery systems.

Novel In Vitro Models for Subcutaneous Administration of Drugs: Transport Properties

Julia ParlowResearch scientist: Julia Parlow. MSc
Principal investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Injection into the tissue under the skin is an attractive administration route for many biomolecular drugs available as a result of recent biotechnological progress. The development of drug formulations for this route is challenged by the difficulty to predict the fate of drug formulations after injection due to the complexity of the subcutaneous (SC) environment, the large variability between patients and biomolecular drug properties.

Julia Parlow Research Aim. The aim is to develop methods to study the transport of drug molecules in biorelevant synthetic models of human SC extracellular matrix, and to use the methods to clarify the key factors governing the transport with respect to interaction with the constituents of the matrix and the interstitial fluid.

Outcome. An in vitro method that can be used to predict the rate of drug absorption in humans after subcutaneous administration.

Subcutaneous administration of biotherapeutics: In vitro properties and bioavailability and absorption rate in vivo

Anton NorbergResearch scientist: Anton Norberg, MSc
Principal investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Subcutaneous administration is one of the most important routes of administration for peptide and protein drugs, and its relevance increases in line with the sharp increase in peptide and protein drugs. Today, there is a lack of established in vitro models for studies on drug interactions with the subcutaneous tissue. Instead, the use of animal models has increased despite poor correlation between animal models and humans. Increased understanding of the subcutaneous tissue interactions of peptide and protein drugs will enable new in vitro models and reduce the amount of animal testing.

Aim. To find out how molecular properties of peptide and protein drugs affect their mobility and tendency to aggregate through physicochemical interactions with components of subcutaneous tissue and how these properties affect the rate of absorption and bioavailability of the drug. Another aim is to establish in vitro / in vivo correlation regarding bioavailability and absorption rate of several peptide and protein drugs for later use as parameters in physiologically based pharmacokinetic and biopharmaceutical models.

Outcome. Increased understanding of the behavior of peptide and protein drugs in subcutaneous tissue and the development of new in vitro models to enable prediction of the absorption of subcutaneously administered drugs.

In Vitro Methods for Enhanced Understanding of Peptide Transport in Subcutaneous Tissue

Yassir Al-Tikriti, postdocResearch scientist: Yassir Al-Tikriti, PostDoc
Principal Investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. In contemporary pharmaceutical research, there is a growing emphasis on in vitro methods for predicting drug absorption after subcutaneous administration. These methods offer a more cost-effective and ethical approach compared to in vivo animal studies. My research focuses on developing and implementing experimental methods to study the transport of peptide drugs within a synthetic model replicating the extracellular matrix of subcutaneous tissue.

Aim. To generate data that aids in modeling drug absorption after in vivo administration. The focus is on identifying specific molecular properties that influence the diffusion and transport of peptide drugs within subcutaneous tissue.

Outcome. Attain a deeper understanding of molecular factors influencing peptide drug behavior within subcutaneous tissue, facilitating the development of pharmaceutical products with high bioavailability and low patient variability.

Self-assembly of therapeutic peptides

Ellen Buntzell, PhD StudentResearch scientist: Ellen Brunzell, MSc
Principal Investigator: Associate Professor Magnus Bergström, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Aggregation of peptides in pharmaceutical formulations is a problem that affects the product’s shelf life, safety, and efficacy. Aggregated peptides is, in many cases, linked to increased immunogenicity and altered effect. A deeper understanding of mechanisms, causes, and driving factors behind self-assembly of peptides is meaningful to be able to increase their stability in pharmaceutical formulations. Accumulation of peptide aggregates occurs in several neurodegenerative diseases, and an increased knowledge of aggregation could contribute to the research of these illnesses.

Aim. The aim of the project is to characterize the structure of self-assembled peptides by using small-angle scattering measurements, mainly X-ray and neutron scattering. By comparing our results with in vivo methods, the structure of peptide aggregates and its correlation with biological effects can be investigated.

Outcome. Increased understanding of mechanisms behind self-assembly as way to predict peptide aggregation behaviour, and the significance of aggregation on biological response.

Physiologically based biopharmaceutics modeling for subcutaneous drug administration

Ilse Dubbelboer, PhDResearch scientist: Ilse Dubbelboer, Researcher
Principal Investigator: Assoc. Prof. Erik Sjögren, Department of Pharmaceutical Biosciences, Uppsala University

Scientific and industrial context. The subcutaneous route of administration is important for  current and future biologics. In addition to being the only option for parenteral self-administration, this route also presents many advantages such as the achievement of prolonged release and the possibility for administration of a wide range of formulations. Still, from a drug development perspective, readily available tools for translation of in vitro and pre-clinical data to clinical performance is still lacking.

Aim. To develop a physiologically based biopharmaceutics model for subcutaneous administration based on the interrelationships between physiology, the pharmacologically active substance and the drug delivery system.

Outcome. A freely accessible physiologically based biopharmaceutics model for subcutaneous drug administration.

Investigation of the relationship between the in vitro properties of different subcutaneously administered peptides and their bioavailability and absorption in vivo

David Juriga, ResearcherResearch scientist: Dávid Juriga, Researcher
Principal investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Subcutaneous injection of therapeutical peptides and proteins is one of the major administration routes and its relevance is rapidly increasing. However, the fraction reaching the circulation is quite low while the immunological response can be significant. Understanding the fate of the injected peptides is still a big challenge since the correlation between the animal experiments and the outcomes of preclinical studies is poor. Moreover, no appropriate in vitro methods have been developed for subcutaneous delivery comparable to the ones established for example for oral administration.

Aim. The aim of the project, is to establish the correlation between in vitro and in vivo experiments by using subcutaneously administered peptides that are promising in cancer therapy. By understanding the key parameters, the development of the in vitro model system to mimic the complexity of the adipose tissue is also in the focus of the project.

Outcome. Better understanding of the correlation between the physicochemical properties of the peptides and their behavior in subcutaneous tissue, as well as an in vitro model system to predict the fate of therapeutical peptides after injection.

Improving FRAP data analysis

Research scientist: Jonas Gernandt, PhDResearch scientist: Jonas Gernandt, PhD
Principal investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Fluorescence recovery after photobleaching (FRAP) is a well-established method for measuring self-diffusion in a complex environment. Despite the popularity of the technique, fast and user-friendly software employing the latest developments in FRAP data analysis methodology is not publicly available.

Aim. The project aims to make the latest and most powerful FRAP data analysis methods readily accessible to scientists at little or no cost in workload.

Outcome. Upon completion of the project, a free, open-source tool for high-throughput analysis of FRAP experiments by modern techniques will be made available to the public.

Completed projects

Amphiphilic Drugs in Microgels

Yassir Al-Tikriti portrait photoResearch scientist: Yassir Al-Tikriti, MSc
Principal Investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. Amphiphilic drug molecules is an important group of active substances which are commonly used in cancer therapy, as antidepressants and antihypertensive agents. These molecules have properties in common with regular micelle-forming surfactants but the relationships between their molecular structure and self-assembling properties are not well understood. Polyelectrolyte microgels are interesting as carriers of amphiphilic drugs. To realize their potential as drug delivery systems it is necessary to study the basic principles governing the drug loading and release properties.

Aim. To relate the microstructure and thermodynamic stability of drug self-assemblies in microgels to the molecular properties of drugs and microgel networks and to the mechanisms and kinetics of release under physiological conditions.

Outcome. Release models that contribute to the development of novel release systems for amphiphilic drugs.

Immunogenicity of synthetic long peptides and the role of formulation and structure for efficacy and toxicity

Martin LordResearch scientist: Martin Lord, PhD
Principal investigator: Assistant Professor Sara Mangsbo, Department of Pharmaceutical Biosciences

Scientific and industrial context. To combat bacterial and viral infections, and as of recent, certain forms of cancer, vaccination has become an instrumental tool for eliciting disease-specific adaptive immune responses. One approach is to implement synthetic long peptides (SLPs), which exclusively encompass the immunogenic epitopes derived from one of these proteins, but often also including T and B cell epitopes to evoke a stronger immune stimulation. Thus, making peptide vaccines both more selective and faster to produce than conventional vaccines for pharmaceutical companies and research institutes.

Aim. This project aims to characterize a set of SLPs derived from the SARS-CoV-2 virus, and other peptides by input from industry parties, with respect to to secondary structure, electrostatic charge, and hydrophobicity and how formulation impacts these parameters and their immunogenicity. Longer synthetic peptides can harbor multiple HLA-specific T cell epitopes and formulation and structure could impact efficacy and toxicity.

Outcome. This study will lead to an increased understanding of optimal vaccine formulations for SLPs that best preserve the functional properties but also enhances lymph node drainage by non-cellular transportation within the extracellular matrix. In addition to a potential vaccine, these peptides are also used in assays for predicting T cell responses to SARS-CoV-2 (outside SweDeliver) in a KAW/SciLifeLab funded project.

Novel in vitro methods to understand transport properties of biologics

Enamul Mojumdar, forskareResearch scientist: Enamul Mojumdar, Researcher
Principal investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Aim. To develop in vitro methods to understand transport properties of biologics, e.g., peptides, antibodies etc. on a synthetic hydrogel model of the extracellular matrix of subcutaneous tissue.

Novel In Vitro Models for Subcutaneous Administration of Drugs

Agnes RodlerResearch scientist: Agnes Rodler, PhD
Principal Investigator: Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University

Scientific and industrial context. In drug delivery, the subcutaneous route increasingly supersedes the oral and intravenous routes of drug administration. Contrary to the latter two ways of delivery, there is lack of standardised in vitro model for robust prediction of in vivo absorption and bioavailability of drugs administered subcutaneously.

Agnes research

Aim. By developing a physiologically relevant model of the extracellular matrix we have improved the mechanistic understanding of subcutaneous injection to facilitate the innovation and development of formulations with high bioavailability of the active pharmaceutical ingredient and small variability between patients.

This model targets to identify biophysical factors which affect molecular transport through the interstitial space and to elucidate to which extent drug-extracellular matrix interactions are size- or charge related.

Outcome. An in vitro model capable of predicting in vivo behaviour of subcutaneous injection.

Last modified: 2023-11-23