Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

Abstract

Background: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection. Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli , but the extent of the permeation was not greater than that enabled by hypodermic injection. Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection.

A method to improve the efficacy of topical eflornithine hydrochloride cream

“…In vitro permeation assay using Franz diffusion cell apparatus (PermeGear, Inc., Hellertown, PA) was completed as previously described (Kumar et al 2012; Kumar et al 2011; Naguib, Kumar, & Cui 2014) using the lower dorsal skin of C57BL/6 mice. Hair was trimmed using an electric clipper 24 h before the collection of the skin.…”

“…The receiver compartment contained 5 ml of water and was maintained at 37°C with a Haake SC 100 Water Circulator (ThermoScientific, Wellington, NH). The hair-trimmed skin was treated with a Dermaroller ® microneedle roller as previously described before it was mounted onto the Franz diffusion cells (Kumar et al 2011; Naguib, Kumar, & Cui 2014). The skin sample was placed onto the flat surface of a balance, and the microneedle roller was rolled in four perpendicular directions over the skin surface, 5 times each for a total of 20 times, with an applying pressure of 350–400 g, which was constantly measured using the balance while the roller was rolled.…”

“…The method described herein relies on the pre-treatment of the skin with microneedles prior to the application of the cream. Microneedles have been successfully used previously to improve the transdermal permeation of small molecules, large molecules, and even nanoparticles (Kim, Park, & Prausnitz 2012; Kumar et al 2012; Kumar et al 2011; Naguib, Kumar, & Cui 2014; Park et al 2010; Prausnitz 2004). Microneedle-based transcutaneous drug delivery relies on creating micro-sized holes in the stratum corneum (Kumar et al 2011; Naguib, Kumar, & Cui 2014; Park et al 2010).…”

“…Microneedles have been successfully used previously to improve the transdermal permeation of small molecules, large molecules, and even nanoparticles (Kim, Park, & Prausnitz 2012; Kumar et al 2012; Kumar et al 2011; Naguib, Kumar, & Cui 2014; Park et al 2010; Prausnitz 2004). Microneedle-based transcutaneous drug delivery relies on creating micro-sized holes in the stratum corneum (Kumar et al 2011; Naguib, Kumar, & Cui 2014; Park et al 2010). We hypothesized that pre-treatment of the skin with microneedles before the topical application of the eflornithine cream will augment eflornithine’s ability to inhibit hair re-growth, because the microneedles can breach the stratum corneum barrier and increase the diffusion of eflornithine to the hair follicles in the viable dermis layer.…”

“…We hypothesized that pre-treatment of the skin with microneedles before the topical application of the eflornithine cream will augment eflornithine’s ability to inhibit hair re-growth, because the microneedles can breach the stratum corneum barrier and increase the diffusion of eflornithine to the hair follicles in the viable dermis layer. The microneedle roller used in this study is already available on the market for human use for cosmetic and other dermatological applications (Bariya et al 2012; Kumar et al 2012; Kumar et al 2011; Naguib, Kumar, & Cui 2014). …”