A Bilayer Microarray Patch (MAP) for HIV Pre-Exposure Prophylaxis: The Role of MAP Designs and Formulation Composition in Enhancing Long-Acting Drug Delivery

Abstract

Microarray patches (MAPs) have shown great potential for efficient and patient-friendly drug delivery through the skin; however, improving their delivery efficiency for long-acting drug release remains a significant challenge. This research provides an overview of novel strategies aimed at enhancing the efficiency of MAP delivery of micronized cabotegravir sodium (CAB Na) for HIV pre-exposure prophylaxis (PrEP). The refinement of microneedle design parameters, including needle length, shape, density, and arrangement, and the formulation properties, such as solubility, viscosity, polymer molecular weight, and stability, are crucial for improving penetration and release profiles. Additionally, a bilayer MAP optimization step was conducted by diluting the CAB Na polymeric mixture to localize the drug into the tips of the needles to enable rapid drug deposition into the skin following MAP application. Six MAP designs were analyzed and investigated with regard to delivery efficiency into the skin in ex vivo and in vivo studies. The improved MAP design and formulations were found to be robust and had more than 30% in vivo delivery efficiency, with plasma levels several-fold above the therapeutic concentration over a month. Repeated weekly dosing demonstrated the robustness of MAPs in delivering a consistent and sustained dose of CAB. In summary, CAB Na MAPs were able to deliver therapeutically relevant levels of drug.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies

“…The bottom of the MAP tips cannot be fully inserted into the skin. To efficiently deliver drugs and potentially reduce drug waste in MAPs, the drug was designed to be loaded only into the tip layer. , To avoid drug diffusion to the baseplate and reduce wearing time, only a small amount of drug-free polymer was used for the second layer to connect with the MAP tips and 3D-printed supported third layer. This trilayer design could allow short wearing times to completely detach the dissolving tips from the baseplate. , Facilitated tip detachment can potentially reduce wearing time and allow the delivery of the drug intradermally in a short duration of MAP application to the patient, consequently improving patient compliance.…”

“…To efficiently deliver drugs and potentially reduce drug waste in MAPs, the drug was designed to be loaded only into the tip layer. 63 , 64 To avoid drug diffusion to the baseplate and reduce wearing time, only a small amount of drug-free polymer was used for the second layer to connect with the MAP tips and 3D-printed supported third layer. This trilayer design could allow short wearing times to completely detach the dissolving tips from the baseplate.…”

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

“…The reduced C max minimizes the risk of peak-related toxicities, especially important for drugs with a narrow therapeutic window. Meanwhile, the extended MRT indicates a sustained drug release profile, which is crucial for chronic conditions like HIV/AIDS to maintain consistent drug levels, thereby improving treatment efficacy and patient compliance . This could lead to reduced dosing frequency, enhancing patient adherence–a significant benefit in lifelong prevention/treatment for diseases such as HIV/AIDS .…”

“…Meanwhile, the extended MRT indicates a sustained drug release profile, which is crucial for chronic conditions like HIV/AIDS to maintain consistent drug levels, thereby improving treatment efficacy and patient compliance. 111 This could lead to reduced dosing frequency, enhancing patient adherence−a significant benefit in lifelong prevention/treatment for diseases such as HIV/AIDS. 112 These findings are particularly relevant for the development of new drug formulations, where maintaining therapeutic drug concentrations for extended periods is key to therapeutic efficacy.…”