Oleogel-mediated transdermal delivery of white emitting NaYF4 conjugated with Rose Bengal for the generation of reactive oxygen species through NIR-upconversion.

The transdermal route for the delivery of therapeutic agents to the inner skin tissues for non-invasive photodynamic therapy; though constitutes a desired modality for treating skin cancer, the success has been limited due to the insurmountable nature of the stratum corneum (SC). In this context, for the first time we report the localization of photosensitizer-conjugated upconversion (UC) particles to the deeper dermal region by overcoming SC through an oleogel-mediated transport mechanism for NIR-induced photodynamic production of reactive oxygen species (ROS). We developed soybean oil and stearic acid based oleogels by incorporating photoluminescent white light emitting NaYF4 (WEN) upconversion (UC) particles conjugated with Rose Bengal (RB), termed as WEN-RB-G. Similarly, we fabricated another type of oleogel by incorporating Li+ doped WEN based UC particles (RB conjugated), with 10 times more photoluminescence intensity, termed as LiWEN-RB-G. Based on the skin permeation enhancing effect of the constituents of the oleogels, we demonstrated the permeation of these two types of conjugated particles in microgram scale through the full thickness of the pig ear skin model within 48 h. The localization of the conjugated particles throughout the skin tissue including dermal and epidermal region was confirmed by confocal microscopy. We also conducted a comparative assessment on WEN-RB-G and LiWEN-RB-G for the suitability of ROS generation and bioimaging under NIR activation. The 'proof of principle' concept reported here is expected to frame a gateway in future for NIR-induced photo-theranostics targeting skin cancer.

Transdermal Delivery of Gold Nanoparticles by a Soybean Oil-Based Oleogel under Iontophoresis.

Developing a facile mechanism for transporting nanoparticles across the whole skin by overcoming the stratum corneum is a challenging task. Herein, a stimuli-responsive and noninvasive transport of gold nanoparticles (AuNPs) has been reported through the fabrication of AuNP-incorporated soybean oil-based oleogels (AuG) using stearic acid as a gelator. A series of AuG was formulated by incorporating different proportions of AuNPs and a fixed amount of ciprofloxacin hydrochloride (drug) to establish that the composition with the highest concentration of AuNP (d-AuG4) was associated with the best iontophoretic response, validated via the corresponding in vitro drug release under AC field-induced iontophoresis. The sample d-AuG4 exhibited both drug and AuNP permeation across the whole pig ear skin thickness within as early as 1 h under the iontophoresis condition. With relevant control experiments, it was shown that the transport of AuNPs through the stratum corneum tissue and across the whole skin was possible upon the simultaneous fulfillment of two conditions: the presence of a skin permeation enhancer (stearic acid) within the oleogel and iontophoresis. While the literature reported that the permeation time for any free inorganic nanoparticle through the full-skin thickness varied within a few days, the permeation enhancement technique developed here reduced the corresponding delivery time for the AuNPs to a few hours. The extent of AuNP permeation that occurred in the microgram (per cm-2) scale was found to be affected by the duration of iontophoresis, suggesting that AuNPs' rapid transdermal entry can be simultaneously triggered and modulated by iontophoretic conditions.

Magnetic nanoparticle incorporated oleogel as iontophoretic drug delivery system.

In this article, we validated the use of electric current as an external stimulus to induce an enhancement of drug release from magnetic nanoparticle (MNP) incorporated organogels (magnetogel) under iontophoretic conditions. For this purpose, we adopted a simple, two-step synthesis route to incorporate magnetic (Fe3O4) nanoparticles (MNP) and ciprofloxacin hydrochloride within the network of a soybean oil-based oleogel using stearic acid as gelator. We fabricated a series of MNP incorporated oleogels by varying the wt% of MNPs while keeping a constant weight ratio of soybean oil:stearic acid. The microstructures of the magnetogels were analyzed in MNP concentration-dependent manner by optical microscopy, powder X-ray diffraction, FTIR, mechanical, and electrical studies. Detailed analysis of the electrical properties revealed that the gel sample with a maximum proportion of MNP (S4) allowed the maximum passage of current through it among all the compositions. Under the iontophoretic environment of the active condition, we observed nearly 2.5 fold increase in cumulative drug release in case of sample S4 compared to the corresponding passive condition. These observations suggested that in future, our magnetogel formulation can be further developed as AC field induced 'remote controlled' agent for therapeutic application.