According to the literature, nanoparticle ��-potentials above 30 mV or below -30 mV are considered stable.20 As shown in Table 1, all nanoparticles, are near -30 mV indicating that they selleck chem are stable. Effects of lyophilization on core + shell nanoparticles Lyophilization is an effective way to prevent the release of therapeutics loaded into PLGA nanoparticles during long-term storage.10,11 However, if not performed correctly, lyophilization can result in aggregation of the PLGA nanoparticles that prevents resolubilization of the clumped nanoparticles (Fig. 2).10,11 We used TEM imaging to visually confirm that well-defined spherical PLGA and PLGA core + pNIPAM shell nanoparticles were successfully fabricated (Fig. 2). However, as also observed by others,10,11 TEM imaging showed that lyophilization caused the PLGA nanoparticles to form aggregates (Fig.
2). This aggregation resulted in an inability to measure diameter and ��-potential of post-lyophilized PLGA nanoparticles. In contrast, encapsulation of PLGA nanoparticles with pNIPAM shells prevented aggregation of the PLGA nanoparticles following lyophilization, further confirming that the pNIPAM shell fully encapsulated the PLGA core. Additionally, we found that lyophilization of the core + shell nanoparticles does not affect their size or ��-potential at 25��C or 37��C (Table 1). Figure 2. Transmission electron microscope images of the various nanoparticles both pre- and post-lyophilization. Scale bars = 250 nm.
Responses of core + shell nanoparticles to dynamic environmental stimuli To further assess the response of our core + shell nanoparticles to temperature-based environmental stimuli, we used dynamic light scattering to measure the diameter of our core + shell nanoparticles as they were exposed to a dynamic range of temperatures from 20��C to 50��C to 20��C. We found that the core + shell nanoparticles readily respond within this temperature range with all core + shell nanoparticle types decreasing in diameter as the temperature was raised above their LCST (Fig. 3). This response was reversible, as the nanoparticles returned to their original diameter when the temperature was lowered back below their LCST. Additionally, the LCST of the pNIPAM shell was tuned by modifying the amount of acrylic acid that was incorporated as a co-monomer. As more acrylic acid was incorporated, the LCST of pNIPAM increased (Fig.
3). The core + shell nanoparticles with 0 mol% acrylic acid exhibited an LCST at ~31�C32��C, while the 1 mol% acrylic acid had an LCST at ~33�C34��C, and the core + shell nanoparticles with 5 mol% acrylic acid had an LCST at ~35��C (Fig. 3). This trend has previously been established in the literature.19,21 In the future, these core + shell nanoparticles Carfilzomib could be engineered to respond to different environmentally based stimuli in addition to temperature by changing the co-monomer composition of the pNIPAM.14 Figure 3.