Related Experiment Video
Updated: Jun 10, 2025
18:57
Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
46.2K
Small scale model for predicting transportation-induced particle formation in biotherapeutics
Urška Pečarič Strnad1, Petra Zalokar1, Natan Osterman2
1Biologics Drug Product, Technical Research and Development, Global Drug Development, Novartis, Kolodvorska 27, Mengeš, Slovenia.
Colloids and Surfaces. B, Biointerfaces
|October 12, 2024
Summary
Protein aggregation at air-liquid interfaces is a challenge. This study shows that adsorption rate and surface film dynamics predict particle formation, aiding biopharmaceutical stability studies.
Area of Science:
- Biophysical Chemistry
- Colloid Science
- Biopharmaceutical Science
Background:
- Proteins adsorb and unfold at air-liquid interfaces, forming viscoelastic films.
- Surface agitation can disrupt these films, leading to undesirable protein aggregation.
- Protein aggregates pose risks, especially in biopharmaceutical applications.
Purpose of the Study:
- To predict surface-mediated protein aggregation in biopharmaceutical solutions.
- To understand the impact of adsorption dynamics on protein solution stability.
- To develop improved biopharmaceutical stability studies simulating transport conditions.
Main Methods:
- Brewster angle microscopy to study interfacial films.
- Micro-flow imaging, light scattering, and size exclusion chromatography for aggregation monitoring.
- Analysis of adsorption rate versus surface turnover rate.
Main Results:
- Protein particle formation is driven by the ratio of adsorption rate to surface turnover rate.
- Surface film dynamics during quiescent phases directly influence aggregation.
- Adsorption dynamics at the air-liquid interface significantly impact protein solution stability.
Conclusions:
- Predicting protein aggregation is crucial for biopharmaceutical handling and stability.
- Understanding interfacial dynamics provides insights into colloidal and biological systems.
- Learnings can inform the design of novel, small-scale biopharmaceutical stability studies.
More Related Videos
Related Concept Videos
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
33
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
33
01:26Pharmacokinetic Models: Comparison and Selection Criterion
47
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
47
01:20Pharmacokinetic Models: Overview
603
Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
603
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
35
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
35
01:06Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
62
Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
62
00:57Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models
69
Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...
69