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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
New Cellular Models to Support Preclinical Studies on ICAM-1-Targeted Drug Delivery
Marco Vigo1,2, Elena Haro-Martínez1, Eloy Ruiz1
1Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain.
Abstract:
Intercellular adhesion molecule 1 (ICAM-1) is a cell-surface protein actively explored for targeted drug delivery. Anti-ICAM-1 nanocarriers (NCs) target ICAM-1-positive sites after intravenous injection in animal models, but quantitative mechanistic examination of cellular-level transport in vivo is not possible. Prior studies in human cell cultures indicated efficient uptake of these formulations via cell adhesion molecule-(CAM)-mediated endocytosis. However, ICAM-1 sequence differs among species; thus, whether anti-ICAM-1 NCs induce similar behavior in animal cells, key for intracellular drug delivery, is unknown. To begin bridging this gap, we first qualitatively verified intracellular transport of anti-ICAM-1 NCs in vivo and then developed new cellular models expressing ICAM-1 from mouse, dog, pig, and monkey, species relevant to pharmaceutical translation and veterinary medicine. ICAM-1 expression was verified by flow cytometry and confocal microscopy. These cells showed specific targeting compared to IgG NCs or cells treated with anti-ICAM-1 blocker. Anti-ICAM-1 NCs entered cells in a time- and temperature-dependent manner, with kinetics and pathway compatible with CAM-mediated endocytosis. All parameters tested were strikingly similar to those from human cells expressing ICAM-1 endogenously. Therefore, this new cellular platform represents a valuable tool that can be used in parallel to support in vivo studies on ICAM-1-targeted NCs during pharmaceutical translation.
Insights
New cell models show anti-ICAM-1 nanocarriers behave similarly across species, aiding drug delivery research. This validates their use in preclinical studies for targeted therapies.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Drug Delivery
Background:
- Intercellular adhesion molecule 1 (ICAM-1) is a cell-surface protein targeted for drug delivery.
- Anti-ICAM-1 nanocarriers (NCs) show promise but their behavior in animal cells is not well understood due to species-specific ICAM-1 differences.
Purpose of the Study:
- To investigate the cellular uptake and transport mechanisms of anti-ICAM-1 nanocarriers in animal cells.
- To develop and validate novel cellular models expressing ICAM-1 from relevant animal species for pharmaceutical translation.
Main Methods:
- Qualitative in vivo assessment of anti-ICAM-1 NC transport.
- Development of cell lines expressing ICAM-1 from mouse, dog, pig, and monkey.
- Verification of ICAM-1 expression using flow cytometry and confocal microscopy.
- Assessment of NC uptake kinetics and temperature dependence.
Main Results:
- Targeted uptake of anti-ICAM-1 NCs was observed in engineered animal cell lines, distinct from control IgG NCs.
- NC internalization exhibited time- and temperature-dependent kinetics consistent with CAM-mediated endocytosis.
- Cellular transport parameters in animal cells closely mirrored those in human cells expressing ICAM-1.
Conclusions:
- The developed cellular models accurately mimic ICAM-1-mediated nanocarrier uptake in various species.
- This platform is a valuable tool for parallel in vivo and in vitro studies of ICAM-1-targeted nanocarriers.
- Findings support the use of anti-ICAM-1 nanocarriers in pharmaceutical translation and veterinary medicine.
