Intradermal delivery of imiquimod using polymeric microneedles for basal cell carcinoma.

Despite being one of the most efficacious drugs used in the treatment of basal cell carcinoma (BCC), imiquimod has limited cutaneous permeation. The current work presents the development of polyvinylpyrrolidone-co-vinyl acetate (PVPVA) microneedles loaded with imiquimod for improving intradermal delivery of imiquimod for the treatment of nodular BCC. In vitro permeation studies, using full thickness ex vivo porcine skin were used to evaluate the effectiveness of these imiquimod loaded polymeric microneedles in comparison to the topical application of commercial Aldara™ cream. HPLC analysis demonstrated similar intradermal permeation of imiquimod from Aldara™ cream and imiquimod-loaded microneedles despite the microneedle having a six-fold lower drug loading than the clinical dose of Aldara™ used for BCC management. In addition, ToF-SIMS analysis of skin cross sections demonstrated intradermal localisation of imiquimod following microneedle-based delivery while the Aldara™ treated skin showed the drug localised predominantly within the stratum corneum. ToF-SIMS analysis also demonstrated intradermal co-localisation of the PVPVA polymer, used in fabricating the microneedle, with imiquimod within the microneedle channels in a label-free manner. This study demonstrates that a polymeric microneedle system may be a viable approach to improving the intradermal delivery of imiquimod for the treatment of nodular BCC with lower drug loading.

Intradermal and transdermal drug delivery using microneedles - Fabrication, performance evaluation and application to lymphatic delivery.

The progress in microneedle research is evidenced by the transition from simple 'poke and patch' solid microneedles fabricated from silicon and stainless steel to the development of bioresponsive systems such as hydrogel-forming and dissolving microneedles. In this review, we provide an outline on various microneedle fabrication techniques which are currently employed. As a range of factors, including materials, geometry and design of the microneedles, affect the performance, it is important to understand the relationships between them and the resulting delivery of therapeutics. Accordingly, there is a need for appropriate methodologies and techniques for characterization and evaluation of microneedle performance, which will also be discussed. As the research expands, it has been observed that therapeutics delivered via microneedles has gained expedited access to the lymphatics, which makes them a favorable delivery method for targeting the lymphatic system. Such opportunity is valuable in the area of vaccination and treatment of lymphatic disorders, which is the final focus of the review.

Expanding the applications of microneedles in dermatology.

Since the first patent for microneedles was filed in the 1970s, research on utilising microneedles as a drug delivery system has progressed significantly. In addition to the extensive research on microneedles for improving transdermal drug delivery, there is a growing interest in using these devices to manage dermatological conditions. This review aims to provide the background on microneedles, the clinical benefits, and challenges of the device along with the potential dermatological conditions that may benefit from the application of such a drug delivery system. The first part of the review provides an outline on benefits and challenges of translating microneedle-based drug delivery systems into clinical practice. The second part of the review covers the application of microneedles in treating dermatological conditions. The efficacy of microneedles along with the limitations of such a strategy to treat diseased skin shall be addressed.

Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment.

Basal cell carcinoma (BCC) is the most common skin cancer in humans. Topical treatment with imiquimod provides a non-invasive, self-administered treatment with relatively low treatment cost. Despite displaying excellent efficacy, imiquimod is only licensed by the FDA for superficial BCC. The current work employed HPLC and ToF-SIMS analysis to provide a novel assessment of imiquimod permeation from Aldara™ cream in skin depth and lateral distribution. Using Aldara™ cream and in vitro Franz cell studies with subsequent HPLC analysis, it is apparent that most of the topically applied imiquimod cream is left on the skin surface with more than 80% of the drug being recovered from skin wash. In addition, ToF-SIMS chemical imaging of recovered tape stripped skin samples illustrated significant detection of imiquimod signal over the entire skin area for the upper tape strips, whereas the deeper strips show large portions of the skin area without detected imiquimod. Given the limited permeation depth and non-uniform permeation observed at tape strips 6-18 when applied as a topical imiquimod cream, a permeation enhancement strategy utilising a skin pre-treatment with a microneedle device was investigated as a method to improve intradermal delivery. The recovered amount of imiquimod in tape strips and remaining skin determined by HPLC was approximately three times higher when Aldara™ was applied on microneedle pre-treated skin relative to intact skin. The ToF-SIMS ion images of the tape strips and cross-sections illustrated the existence of imiquimod in the microchannels which then laterally diffuses to peripheral epidermal strata. The current work demonstrates the first known attempt to enhance intradermal delivery of imiquimod using a microneedle device as well as underscoring the complementary role of ToF-SIMS analysis in chemically mapping imiquimod permeation into the skin with high sensitivity.