Noteworthy, FITC fluorescence was confined to microchannels ( Fig. 9b), while diffuse Rh B fluorescence

was clearly observed around the pores and more extensively in Autophagy inhibitor cost deeper skin layers ( Fig. 9a). Depth penetration profiling demonstrated relatively deep Rh B permeation with detectable red fluorescence at 190 μm. On the other hand, the green FITC fluorescence was significantly reduced at a depth of 130 μm and almost disappeared at 150 μm ( Fig. 9c and d, respectively). Difference in permeation of Rh B and FITC was further substantiated by modulating the initial dye loading of NPs. While increasing Rh B loading (F6–F8, Table 1) generally resulted in a proportional significant increase in flux (Fig. 10), an increase in FITC loading (F9–F11) had an opposite effect (Fig. 10). Results verified the role of solubility as a primary determinant of the flux of small size permeants across hydrophilic deeper skin layers. Release of a larger amount of the water soluble Rh B dye around the NPs depot sites would build up a larger concentration gradient, the main driving force for transport of soluble permeants [20]. Increasing the concentration of hydrophilic permeants such as naltrexone salts resulted in increased MN-mediated transdermal flux [48]. Although

data for more drugs are needed, drug loading of nanocarriers is a formulation factor

that can be modulated to control permeation of nanoencapsulated drugs with different molecular characteristics BIBW2992 supplier through microporated skin for different skin delivery purposes. Skin permeation data (Table 2) and CLSM imaging (Fig. 9) combined with absence of NPs in the receiver compartment during the study as confirmed by TEM provided sufficient evidence to suggest that only the free dye released from NPs permeated skin layers to the receiver compartment of the diffusion cell. It is worth mentioning that porcine skin barrier function proved to be maintained for 48 h using TEWL measurements [31] which was verified in this study by the absence of NPs in the receiver compartment after 48 h. Further, data see more indicated that post-infiltration of NPs in MN-created microchannels, a process affected largely by NPs characteristics, skin permeation rates of the released dyes were determined primarily by their molecular characteristics. The more hydrophilic Rh B dye permeated MN-treated skin at a significantly greater rate compared to the hydrophobic FITC dye of smaller MW, though both were encapsulated in PLGA NPs with similar properties. Findings tend to indicate that the MN/nanoencapsulation combined approach could be of benefit in enhancing transdermal delivery of hydrophilic drugs and controlling dermal localization of hydrophobic drugs.