TY - JOUR
T1 - Design of triphasic poly(lactic-co-glycolic acid) nanoparticles containing a perfluorocarbon phase for biomedical applications
AU - Swider, Edyta
AU - Staal, Alexander H.J.
AU - van Riessen, N. Koen
AU - Jacobs, Linsey
AU - White, Paul B.
AU - Fokkink, Remco
AU - Janssen, Geert Jan
AU - Van Dinther, Eric
AU - Figdor, Carl G.
AU - De Vries, I. Jolanda M.
AU - Koshkina, Olga
AU - Srinivas, Mangala
N1 - Funding Information:
Authors would like to acknowledge Ad Swolfs for his support during NMR measurements. Prof. Manfred Schmidt and Georg Conrad for providing a HDRC soware for multi-angle light scattering. Jorieke Weiden for the help with cell migration assay. Andor Veltien for the help with 19F MRI imaging. Dr Oya Tagit for the consult and writing support. The MR measurements were supported by NWO Investment Grants 91106021 and BIG (VISTA). This work was supported by the European Research Council (ERC) Starting Grant (CoNQUeST grant no. 336454) and grant 14716 from the Netherlands organization for scientic research NWO-TTW grant. to MS. IJMdV received NWO-Vici 918.14.655. CGF received the NWO Spinoza Grant, ERC Adv Grant PATHFINDER (269019) and Dutch Cancer Society Grant KUN2009-4402.
Publisher Copyright:
© 2018 The Royal Society of Chemistry.
PY - 2018
Y1 - 2018
N2 - Poly(lactic-co-glycolic acid) (PLGA) particles are very widely used, particularly for drug delivery, including commercial clinical formulations. Adding perfluorocarbon (PFC) enables in vivo imaging and quantification of the PLGA particles through 19F NMR, MRS or MRI. PFCs are both hydrophobic and lipophobic at the same time. This property makes their encapsulation in particles challenging, as it requires the addition of a third immiscible phase during the emulsification process. Here we explore how different parameters affect the miniemulsion formation of particles loaded with perfluoro-15-crown-5-ether (PFCE). By changing the concentration of surfactant and type of solvent, we were able to control the radius of synthesized particles, between 85-200 nm. We assessed stability and release from the particles at different pH values, showing that hydrophobic agents are released from the particles by diffusion rather than degradation. With cell experiments, we show that primary human dendritic cells take up the particles without any apparent effect, including on cell migration. In summary, the control of synthesis conditions leads to particles with sufficient PFCE encapsulation, which are suitable for drug loading and cell labeling, and do not affect cell viability or functionality. Finally, these nanoparticles can be produced at GMP-grade for clinical use.
AB - Poly(lactic-co-glycolic acid) (PLGA) particles are very widely used, particularly for drug delivery, including commercial clinical formulations. Adding perfluorocarbon (PFC) enables in vivo imaging and quantification of the PLGA particles through 19F NMR, MRS or MRI. PFCs are both hydrophobic and lipophobic at the same time. This property makes their encapsulation in particles challenging, as it requires the addition of a third immiscible phase during the emulsification process. Here we explore how different parameters affect the miniemulsion formation of particles loaded with perfluoro-15-crown-5-ether (PFCE). By changing the concentration of surfactant and type of solvent, we were able to control the radius of synthesized particles, between 85-200 nm. We assessed stability and release from the particles at different pH values, showing that hydrophobic agents are released from the particles by diffusion rather than degradation. With cell experiments, we show that primary human dendritic cells take up the particles without any apparent effect, including on cell migration. In summary, the control of synthesis conditions leads to particles with sufficient PFCE encapsulation, which are suitable for drug loading and cell labeling, and do not affect cell viability or functionality. Finally, these nanoparticles can be produced at GMP-grade for clinical use.
UR - http://www.scopus.com/inward/record.url?scp=85042046028&partnerID=8YFLogxK
U2 - 10.1039/c7ra13062g
DO - 10.1039/c7ra13062g
M3 - Article
VL - 8
SP - 6460
EP - 6470
JO - RSC advances
JF - RSC advances
SN - 2046-2069
IS - 12
ER -