Polymeric nanospheres have the ability to encapsulate drugs, but their clinical success as drug delivery vehicles has been limited. To understand this failure, we are focusing on the interactions of nanospheres with proteins and tissue surfaces. Here we investigated the adsorption behavior of nanospheres along with plasma proteins onto model surfaces using quartz crystal microbalance with dissipation (QCM-D). Nanospheres were prepared from Pluronic F-127, PEG-poly(caprolactone) (PCL) and an A-B-A triblock copolymer with mPEG(5k) as the A blocks and an alternating copolymer of desaminotyrosyl-tyrosine octyl ester and suberic acid oligomers, oligo(DTO-SA), as the B block. Substrates were prepared from polymers with different degree of PEGylation (0, 1 and 15%). DTO-SA nanospheres assembled into a close-packed structure on non-PEGylated substrates, and formed a continuous film, thinner than the size of the nanospheres on PEGylated substrates suggesting unraveling of the PEG corona and disassembly of the nanospheres. Also, the adsorption was concentration-dependent, the final thickness being attained at exponentially longer times at lower concentrations. Such substrate- and concentration-dependent behavior was not observed with Pluronic F-127 and PEG-PCL nanospheres, but the adsorbed thicknesses were much smaller than the hydrodynamic diameter (~ 15 vs. 50 nm). These results are indicative of significant deformation of the nanospheres upon adsorption. The nature of the protein corona was examined from sequential and simultaneous adsorption of nanospheres and key plasma proteins, albumin and fibrinogen. The interactions of the proteins with nanospheres with similar PEG shell show that the composition of the protein corona is determined by the nature of the core as well. Thus, the instability of the nanospheres upon adsorption that affects drug release and the nature of the protein corona that affects transport across cell walls are just two of the factors that can be measured and taken into account in designing nanospheres for drug delivery applications.

Role of the interactions of nanospheres with proteins and substrates on drug delivery investigated using quartz crystal microbalance

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.