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A Rapid and Quantitative Fluorimetric Method for Protein-Targeting Small Molecule Drug Screening
Published on: October 16, 2015
Algorithm-driven high-throughput screening of colloidal nanoparticles under simulated physiological and therapeutic
Ashwinkumar A Bhirde1, Sivasish Sindiri2, Gina N Calco3
1Laboratory of Biological Chemistry, Division of Biotechnology Review and Research IV, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Serge.Beaucage@fda.hhs.gov Ashwinkumar.Bhirde@fda.hhs.gov.
Developing new algorithms for nanoparticle size measurement accelerates stability assessments for cancer drug delivery. This high-throughput method rapidly evaluates nanoparticle behavior under physiological conditions, crucial for clinical translation.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- Colloidal nanoparticles show promise as cancer drug carriers and phototherapeutics.
- Nanoparticle stability under physiological and phototherapeutic conditions is critical for clinical translation.
- Current methods for assessing nanoparticle stability are time-consuming.
Purpose of the Study:
- To design and implement novel algorithms for high-throughput hydrodynamic size measurements of colloidal nanoparticles.
- To assess nanoparticle stability and aggregation profiles under physiological and phototherapeutic conditions.
- To evaluate the impact of surface coatings on nanoparticle-protein interactions.
Main Methods:
- Development of unique algorithms for high-throughput hydrodynamic size measurements.
- Utilizing bovine serum albumin as a protein model to assess nanoparticle-protein interactions.
- Comparing the behavior of uncoated and PEGylated nanoparticles.
Main Results:
- The developed algorithms provide clinically-relevant particle size distribution assessments.
- Uncoated nanoparticles showed significant association with bovine serum albumin, indicating potential instability.
- PEGylated nanoparticles exhibited minimal association with bovine serum albumin, suggesting improved stability.
- The algorithm-based method significantly reduces the time required for size measurement protocols from years to days.
Conclusions:
- Algorithm-driven high-throughput size screening offers a rapid and meaningful method for assessing nanoparticle stability.
- This approach facilitates the evaluation of nanoparticle behavior under conditions relevant to drug delivery and phototherapeutics.
- The method accelerates the development and clinical translation of nanoparticle-based therapies.

