AAPS PharmSciTech

, Volume 19, Issue 4, pp 1672–1680 | Cite as

Nanoparticles for Protein Sensing in Primary Containers: Interaction Analysis and Application

  • Víctor Pérez Medina Martínez
  • Carlos E. Espinosa-de la Garza
  • Diego A. Méndez-Silva
  • Mariana Bolívar-Vichido
  • Luis F. Flores-Ortiz
  • Néstor O. PérezEmail author
Research Article


Silver nanoparticles (AgNPs) are known to interact with proteins, leading to modifications of the plasmonic absorption that can be used to monitor this interaction, entailing a promising application for sensing adsorption of therapeutic proteins in primary containers. First, transmission electron microscopy in combination with plasmonic absorption and light scattering responses were used to characterize AgNPs and protein-AgNP complexes, including its concentration dependence, using two therapeutic molecules as models: a monoclonal antibody (mAb) and a synthetic copolymer (SC). Upon interaction, a protein corona was formed around AgNPs with the consequent shifting and broadening of their characteristic surface plasmon resonance (SPR) band (400 nm) to 410 nm and longer wavelenghts. Additional studies revealed secondary and three-dimensional structure modifications of model proteins upon interaction with AgNPs by circular dichroism and fluorescence techniques, respectively. Based on the modification of the SPR condition of AgNPs upon interaction with proteins, we developed a novel protein-sensing application of AgNPs in primary containers. This strategy was used to conduct a compatibility assessment of model proteins towards five commercially available prefillable glass syringe (PFS) models. mAb- and SC-exposed PFSs showed that 74 and 94% of cases were positive for protein adsorption, respectively. Interestingly, protein adsorption on 15% of total tested PFSs was negligible (below the nanogram level). Our results highlight the need of a case-by-case compatibility assessment of therapeutic proteins and their primary containers. This strategy has the potential to be easily applied on other containers and implemented during early-stage product development by pharmaceutical companies and for routine use during batch release by packaging manufacturers.


Monoclonal antibody Prefilled syringes Primary container Silver nanoparticles Synthetic copolymer 


Funding Information

This work was supported by CONACYT, Mexico (grant PEI CONACYT 2015 220333). CONACYT did not participate in the design of the study or in the collection, analysis, and interpretation of data.


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Víctor Pérez Medina Martínez
    • 1
  • Carlos E. Espinosa-de la Garza
    • 1
  • Diego A. Méndez-Silva
    • 1
    • 2
  • Mariana Bolívar-Vichido
    • 1
  • Luis F. Flores-Ortiz
    • 1
  • Néstor O. Pérez
    • 1
    Email author
  1. 1.Unidad de Investigación y DesarrolloProbiomed, S.A. de C.VTenancingoMéxico
  2. 2.Departamento de Ingeniería en NanotecnologíaUniversidad de La Ciénega del Estado de Michoacán de OcampoSahuayoMéxico

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