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    Drug Delivery

    Polymeric microneedle patches for controlled and systemic delivery of therapeutic nanoparticles

    (L-460) Polymeric microneedle patches for controlled and systemic delivery of therapeutic nanoparticles

    Saturday, October 14, 2023
    9:30 AM – 10:30 AM PDT
    Location: Exhibit Hall - Row L - Poster # 460
    Introduction: Breast cancer is the most commonly diagnosed cancer type, with about 2.3 million new diagnoses per year worldwide. Over 75% of those diagnosed with breast cancer have tumors expressing estrogen receptor alpha (ERα), a protein that is strongly associated with the development and progression of these tumors. While current treatments have been successful in blocking the action of ERα, many tumors have developed a resistance to these treatments, resulting in the recurrence of breast cancers. Selective estrogen receptor degraders such as proteolysis targeting chimeric (PROTAC) drugs take an alternative approach to treating these tumors by degrading ERα and have been shown to be 90% effective in reducing ERα. Unfortunately, however, PROTACs offer very limited oral bioavailability. While intramuscular and intravenous delivery methods used for PROTACs are successful in increasing bioavailability, these methods result in pain at the administration site, lower patient compliance, and frequent dosing that must be administered by a healthcare professional. To overcome these limitations, we propose the use of microneedle patches as a minimally invasive way to achieve systemic circulation of therapeutic nanoparticles. By encapsulating the PROTACs in alginate, a biocompatible and biodegradable polymer, we can modulate release that allows for consistent and pain-free dosing over our desired delivery period.

    Materials and Methods: A 2% solution of alginate loaded with DiI-labeled nanogels was fabricated and used to model PROTAC release. To produce the microneedle patches, this fluorescently labeled alginate was placed in silicone molds and centrifuged in flat bottom tubes. Once the patches were dry, blank alginate was added to create the backing, and the centrifugation and drying processes were repeated. To investigate release, each patch was placed in PBS where samples were taken at 1, 5, 10, 15, 30, 45, and 60 minutes. Nanogel release at each time interval was quantified by comparing fluorescence to a standard curve. After optimization, the DiI label will be replaced with functional ERα targeting PROTACs. To perform an ex vivo release, rat skin was harvested and shaved, and DiI-labeled patches were administered using an applicator. After 60 minutes, the patch was removed, and the skin was imaged.

    Results, Conclusions, and Discussions: Our data shows that the DiI-labeled nanogel microneedle patches are able to achieve an average of 78% release over 60 minutes, demonstrating the potential of this transdermal delivery system to release PROTACs. Ex vivo release on rat skin showed effective permeation of the DiI-labeled nanogels across the outermost layer of skin. Ongoing studies are now exploring the bioactivity of released PROTACs by measuring the depletion of the ERα protein in breast cancer cells using western blotting. Future work will confirm that the biodistribution of PROTACs delivered by microneedle patches is comparable with IV delivery by measuring their efficacy in vivo. Our ultimate goal is to develop a rapid, pain-free method to self-administer PROTAC drugs for the treatment of breast cancer.

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