Immobilization of Telodendrimer

Micelles into SAMs for AFM Imaging For structural characterization via AFM, micelles must be immobilized on surface supports. Immobilized drug delivery vehicles are the key component in therapies using patches [38]. A potential application of immobilized PTX-loaded micelles on Integrase inhibitor surfaces is the development of a new type of PTX eluting stent [39]. The procedure Inhibitors,research,lifescience,medical of immobilization of micelles onto gold surfaces is shown in Scheme 1. HS-PEG5k-CA8 telodendrimer is soluble in water and self-assembles into micelles. PTX is loaded into the micelle via a procedure of solvent evaporation followed by the aqueous dispersion of micelles [40]. Scheme 1 Schematic of surface immobilization of unloaded and paclitaxel loaded HS-PEG5k-CA8 micelles

on Au surfaces. In order to maintain the integrity of micelles on solid surface, gold surfaces were covered by SAMs of AD. The use of AD is based mainly on two considerations: (a) SAMs provide a buffer to dampen collisions and allow full contact between micelles and gold Inhibitors,research,lifescience,medical surfaces and (b) AD can be exchanged by alkane thiol functionalities to enable micelles to anchor onto gold surfaces. As illustrated in Scheme 1, micelles are formed instantly via the self-assembly of telodendrimers dissolved in aqueous solution. The critical micelle concentration of micelles was 5.3μM. The micelles have noncharged surfaces, the Zeta-potential was measured close to zero [21]. Inhibitors,research,lifescience,medical AD SAMs on gold were soaked in micelle solutions, 0.5mg/mL, for 20min. This short exposure resulted in 15.3% surface coverage of micelles Inhibitors,research,lifescience,medical on the gold surface. In the case of PTX-loaded micelles, a concentration of 26.4 mg/mL (weight ratio as 6.4mg PTX: 20mg HS-PEG5k-CA8) was used and the exposure time was typically 1 hour. This led to 29.0% surface coverage of PTX loaded micelle on the gold surface. After deposition, the samples were rinsed with Milli Q water and kept in the water solution before AFM measurement. 3.2. AFM Enables Visualization Telodendrimer Micelles in their Native Media and Detection of Changes upon Uptake of PTX Upon immobilization, AFM imaging is carried out in water media. To attain accurate

Inhibitors,research,lifescience,medical measurements in 3D without significant deformation, tapping mode is utilized, from which height is extracted from topographic images, and lateral boundaries are well defined from phase images. The AFM images in Figure 1 indicate that all micelles, PTX-loaded or unloaded, maintain the geometry of elliptical cap out geometry. Figure1(a) is a 300 × 300nm2 AFM topography image of PTX-loaded micelles on ultraflat Au. Each bright protrusion is a single PTX-loaded micelle. The height of a typical PTX-loaded micelle, as shown in cursor 1, is 4.0nm, measured from the lowest point in the local surroundings to the apex of the micelle. Its lateral boundaries are clearly visible from the AFM phase image shown in Figure1(c). The lateral dimensions are 28.1nm and 33.0nm for short axis and long axis, respectively, as shown in cursors 2 and 3.