Opportunity
Current drug and vaccine delivery systems, particularly for nucleic acid-based therapies like DNA and RNA vaccines, face significant challenges. Conventional methods such as intramuscular (IM) injections often result in low transfection efficiency and require high doses to achieve effective immune responses. Additionally, traditional electroporation techniques, while effective, involve high voltages (>200 V) that cause cell death, pain, and require liquid formulations, which complicate storage and transportation (e.g., "cold chain" requirements for mRNA vaccines). Microneedle-based delivery systems have emerged as minimally invasive alternatives, but they struggle with rapid clearance of nucleic acids and low immunogenicity due to insufficient antigen delivery to antigen-presenting cells (APCs) like dendritic cells. There is a pressing need for a delivery system that combines the precision of microneedles with the efficiency of electroporation, while minimizing invasiveness, pain, and logistical hurdles like cold storage.
Technology
The patent introduces an innovative conductive hydrogel microelectrode (CHME) platform for transdermal drug and vaccine delivery. The system comprises an array of electrically conductive microneedles loaded with nucleic acid vaccines (e.g., DNA or RNA) or other biomacromolecules. These microneedles serve dual roles: (1) as electrodes for low-voltage electroporation (1–90 V) and (2) as carriers for controlled release of encapsulated substances via electro-osmosis. Upon application to the skin, the microneedles penetrate the epidermis, and an electric circuit activates the release of the payload while simultaneously inducing electroporation to enhance cellular uptake. Key innovations include:
- Single-step fabrication: The microneedles are cast from a blend of biocompatible polymers (e.g., polyvinyl alcohol, PVA) and conductive materials (e.g., PEDOT:PSS), enabling scalable production.
- Low-voltage operation: The system uses pulses as low as 1 V, reducing pain and cell damage compared to conventional electroporation.
- Dry-state storage: Vaccines encapsulated in the microneedles remain stable at room temperature, eliminating cold-chain requirements.
Preclinical studies demonstrated that the CHME platform delivers 10-fold higher transfection efficiency than passive diffusion and induces robust immune responses at lower doses (e.g., 10 µg of plasmid DNA vs. 100 µg for IM injection).
Advantages
- Minimally invasive: Eliminates needles and reduces pain.
- High efficiency: Combines electroporation and electro-osmosis for superior transfection and antigen presentation.
- Room-temperature stability: No need for refrigeration, simplifying logistics.
- Versatile: Compatible with DNA, RNA, proteins, and peptides.
- Self-administrable: Designed for ease of use with minimal training.
Applications
- Vaccination: For diseases like COVID-19, cancer (e.g., DNA vaccines), and infectious diseases (e.g., HIV, influenza).
- Cancer immunotherapy: Delivery of tumor-specific antigens to APCs.
- Gene therapy: Transdermal delivery of siRNA or plasmid DNA.
- Research tools: In vitro and in vivo studies requiring precise nucleic acid delivery.
