Disassembly of Nanospheres with a PEG Shell upon Adsorption onto PEGylated Substrates

Abstract

Polymeric nanospheres have the ability to encapsulate drugs and are therefore widely used in drug delivery applications. Structural transformations that affect drug release from nanospheres are governed by the surrounding environment. To understand these effects, we investigated the adsorption behavior of three types of nanospheres onto model surfaces using quartz crystal microbalance with dissipation (QCM-D) and by atomic force microscopy (AFM). Substrates were prepared from polymers with different degrees of PEGylation (0, 1, and 15%). Nanospheres were prepared via self-assembly of block copolymers. Tyrosine-derived nanospheres are A–B–A triblock copolymers with methoxy poly­(ethylene glycol) (PEG) as the A-blocks and an alternating copolymer of desaminotyrosyl-tyrosine octyl ester and suberic acid oligo­(DTO-SA) as the B-block. On non-PEGylated substrates, these nanospheres assembled into a close-packed structure; on PEGylated substrates, the adsorbed nanospheres formed a continuous film, thinner than the size of the nanospheres 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-poly­(caprolactone) (PCL) nanospheres. Since the essential difference among the three nanospheres is the composition of the core, we conclude that the core influences the adsorption characteristics of the nanospheres as a consequence of their disassembly upon adsorption. These results are expected to be useful in designing nanospheres for their efficient transport across vascular barriers and for delivering drugs to their targets.

Recent applications of QCM-D for the design, synthesis, and characterization of bioactive materials

“…Patel et al used polymeric nanospheres and surfaces of varying amounts of PEGylation. 19 They found that nanospheres can bind as whole particles, partially deform on the substrate surface, or completely disassemble Table 1. Characterizable properties of bioactive materials using QCM-D.…”

“…Swelling/degradation 16,22,23 Mechanical/rheological properties 16,22 Nanoparticles Deposition kinetics 19,20,23 Mechanical properties 19,20 Swelling/degradation 23 Biomolecular adhesion 23 Therapeutic delivery 20…”

“…By introducing polymeric nanospheres to layers varying in their PEG percentage, the authors detected (a) the deposition of whole nanoparticles at 0% PEG, (b) deposition and deformation of nanoparticles at 1% PEG, and (c) complete disassembly of particles at 15% PEG. Reprinted with permission from Patel et al 19 Copyright 2020 American Chemical Society. Distinct binding behavior was also observed with lipid nanoparticles at different concentrations.…”

Understanding the Adsorption and Desorption of Sitagliptin Phosphate Monohydrate on SS2343, Glass, and PTFE Using QCM-D and Raman Spectroscopy

“…In recent years, the quartz crystal microbalance with dissipation (QCM-D) has been extensively used in many studies for the evaluation of the interactions of molecules on various surfaces, 15,16 including cleaning of surfaces. 17,18 QCM-D works by mechanical deformation in response to the electric field applied.…”

“…In recent years, the quartz crystal microbalance with dissipation (QCM-D) has been extensively used in many studies for the evaluation of the interactions of molecules on various surfaces, , including cleaning of surfaces. , QCM-D works by mechanical deformation in response to the electric field applied . Therefore, masses as small as in the nanogram range when added or removed from the QCM-D sensor will produce different signals, i.e., in the form of frequency change (Δ f ) and dissipation change (Δ D ) at different resonances .…”