Characterizing Pharmaceutical Interactions with QCM-D
Quartz Crystal Microbalance with Dissipation (QCM-D) is a sensitive and versatile analytical technique used to study thin films, biomolecular interactions, and other surface-related processes. QCM-D can provide valuable insights into the adsorption, interaction, and stability of molecules on a solid surface.
QCM-D monitors the resonance frequency of a quartz sensor as a function of time. The resonance frequency of the sensor depends on its mass, so changes in frequency will reveal changes in the mass coupled to the sensor surface. Energy loss of the system, or dissipation, is also monitored by QCM-D. Changes in dissipation can be used to quantify the viscoelastic properties of soft layers attached to the sensor. Frequency and dissipation changes can be used to analyze molecular interactions with the sensor surface.
Biolin Scientific, a pioneer in QCM-D technology, has commercialized the QSense system and it is the leading QCM-D instrument in the market.
Drug Development
The mass sensitivity at the sub-nanogram level offers a promising potential of this tool in drug discovery or drug development. Some of the research activities that have used Qsense for drug development include:
Drug Delivery
QSense has also been proven to be a cost and time-effective technique for the characterization of Lipid Nanoparticles (LNP) and their drug delivery properties. Several research articles have reported the use of QSense in:
- Analyzing the binding affinities of serum proteins to lipid nanoparticles (LNP) [4]
- Binding and release of biomolecules such as siRNA and mRNA from LNP [5]
- Delivery of LNP to the desired organs. [6]
- Screening of the binding affinity of serum proteins to LNPs in a cell-free environment [7]
- Analyzing surface modification of LNPs [8]
- Interaction of lipids with biologically active molecules including drugs, DNA, and siRNA [9]
- Effect of ApoE binding on the lipid component distribution and the overall LNP structure [24]
- Nanohole arrays for storage of functionalized LNP [25]
- LNP formulation to improve the efficiency of delivery of their nucleic acid payload [26]
- Tethering of microbubbles to supported lipid bilayers using cDNA [27]
- The ability of block copolymer stabilized cubosomes to interact with a biomimetic lipid membrane [28]
Drug–surface interactions:
QSense is invaluable in the characterization of drug formulations – surface interactions during production,
purification, storage, and delivery. Selected examples include,
- Drug interactions with surfaces such as polymers, glass, metals and metal oxides, silicone oil, etc. [10], [11], [12], [13], [14], [15], [16]
- Effect of excipients in mitigating drug-protein adsorption onto surfaces [17]
- Effect of other formulation conditions; concentration, pH, temp, etc. [18]
- Effect of interfaces and interfacial stresses in the development of biologics [19]
List of QCM-D sensors for Drug-surface interaction studies |
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| Plastic Packaging | Polypropylene (PP) Polyvinyl chloride (PVC) Polyethylene terephthalate (PET) Polymethylmethacrylate (PMMA) |
Polyethylene (PE) Low density PE (LDPE) High density PE (HDPE) Linear low density PE (LLDPE) |
| Glass Containers | Borosilicate glass |
Soda-lime glass |
| Bags | Cyclo olefin polymer (COP) |
Cyclo olefin co-polymer (COC) |
| Filter Materials | Polyvinylidene fluoride (PVDF) Polytetrafluoroethylene (PTFE) Polycarbonate (PC) |
Polyethersulfone (PES) Polyethylene terephthalate glycol-modified (PET-G) |
| Pre-Filled Syringes | PDMS (Silicone oil) | |
| Other Relevant Materials | Polystyrene Cellulose Stainless steel L605 SS2343 (Similar to US Standard 316) Ethylene-vinyl Acetate (EVA) |
Nylon Polyurethane Cellulose Acetate Polyacrylonitrile (PAN) |
*Note: Custom sensor surfaces can be made upon request
Biomaterial interaction with human tissue:
Biocompatibility of implants and biomaterials in the human body is key to their successful performance. QSense provides in vitro analysis of implant surface or biomaterial interaction with human blood and tissues at the molecular level.
- Interaction of various eye care formulations on mucin/cell membrane surface [20]
Biosensor Development
The QSense Omni is the latest advancement in QCM technology from the pioneers of the QCM-D technique. With the highest sensitivity of any QCM available on the market, the Omni enables the quantification and monitoring of faster processes involving smaller molecules, which is ideal for investigating biological processes. Over 100 sensor surface materials and coatings are available, supporting the simulation of real biological environments and processes to characterize protein adsorption rates, thin film formation, layer rigidity, calcification, cell attachment, and much more.
- Resolve smaller changes at the sensor surface down to 0.24 ng/cm2
- 5x faster fluid exchange providing faster and sharper sample delivery
- A host of automated features to minimize user-dependent data variation
- Easier workflows and an intuitive new software make QCM-D more accessible to a wider range of users
References
[2] Genentech – Viscoelastic characterization of high concentration antibody formulations using quartz crystal microbalance with dissipation monitoring
[7] AstraZeneca – Screening of the binding affinity of serum proteins to lipid nanoparticles in a cell free environment
[10] Genentech – Adsorption and Aggregation of Monoclonal Antibodies at Silicone Oil–Water Interfaces
[11] Bristol-Myers Squibb – Mechanistic Understanding of Protein-Silicone Oil Interactions
[12] Bristol-Myers Squibb – Adsorption of polypropylene oxide-polyethylene oxide type surfactants at surfaces of pharmaceutical relevant materials: effect of surface energetics and surfactant structures
[13] Bristol-Myers Squibb – Particle Characterization for a Protein Drug Product Stored in Pre-Filled Syringes Using Micro-Flow Imaging, Archimedes, and Quartz Crystal Microbalance with Dissipation
[15] Antibody adsorption and orientation on hydrophobic surfaces
[16] AstraZeneca – The Impact of the Metal Interface on the Stability and Quality of a Therapeutic Fusion Protein
[17] Janssen Pharmaceuticals (Johnson and Johnson) – Quartz Crystal Microbalance as a Predictive Tool for Drug-Material of Construction Interactions in Intravenous Protein Drug Administration
[19] Bristol-Myers Squibb – Overview of the Impact of Protein Interfacial Instability on the Development of Biologic Products
[20] Novartis Pharma – Understanding the adsorption and potential tear film stability properties of recombinant human lubricin and bovine submaxillary mucins in an in vitro tear film model
[22] Amplified QCM-D biosensor for protein based on aptamer-functionalized gold nanoparticles
[25] Development of Nanopackaging for Storage and Transport of Loaded Lipid Nanoparticles.
[27] QCM-D Investigations on Cholesterol–DNA Tethering of Liposomes to Microbubbles for Therapy.