The latter step is a concentration gradient-driven process, SP600125 influenced by the drug molecular characteristics and impeded by diffusional resistances of the microchannels and the tissues beneath [20] and [25]. In a recent study, we reported on the effect of MN array characteristics and application variables on the

in vitro transdermal delivery of Rh B encapsulated in PLGA NPs across full thickness MN-treated porcine skin [10]. In the present work, we aimed at providing more knowledge on the contribution of characteristics of nanocarrier and encapsulated dye to MN-mediated transdermal delivery of nanoencapsulated LY2835219 chemical structure dyes. The skin model used was full thickness porcine ear skin (approximately 1164 μm-thick), a well-established model representing full skin resistance and possessing characteristics similar to those of human skin [35]. Rh B or FITC-loaded NPs prepared at a relatively high emulsion homogenization speed (15,000 rpm)

with 1% w/v DMAB were generally monodisperse with PDI < 0.2 and positively charged due to adsorption of the cationic surfactant. Zeta potential values exceeded 30 mV (36.1–67.6, Table 1), indicating physical stability [36]. This was obvious in TEM images of sample NPs (Fig. 3). FITC NPs prepared with PVA as emulsion stabilizer were negatively charged (−4.5 mV, Table 1). Reduction in the particle size of 20% w/w Rh B-loaded PLGA 50:50 NPs (F1–F3) in the range 422.3–155.2 nm (Table 1) resulted in a significant increase in permeation of Rh B across MN-treated skin (Fig. 4). For instance, a 2.7-fold reduction in the mean diameter of F3 compared to F1 NPs led to a fivefold increase in Q48. It has been demonstrated that permeation characteristics of a NP through microchannels were significantly affected by NPs size relative to the pore size [37]. As the width

of MN-created microchannels is usually in the micron range [23], that is, significantly larger than the size range of test NPs in the present study, and NPs size dependence of Rh B skin permeation can be explained by faster release of the encapsulated second water soluble Rh B from smaller size NPs with larger surface to volume ratio. Particle size is a factor known to affect drug release from polymeric NPs [38]. Further, translocation of PLGA NPs across full thickness human abdominal skin was shown to be NPs size dependent, despite the larger microchannel size [22] and [23]. Combined findings suggest deeper and more extensive influx of smaller NPs through MN-created channels leading to enhanced transdermal delivery of the water soluble dye released at the deeper NPs deposition sites.