Polymeric microarray patches for transdermal delivery of amodiaquine and artesunate: A novel strategy against Plasmodium falciparum

Malaria remains a significant global health burden, particularly in low- and middle-income countries. Artemisinin-based combination therapies (ACTs) are the current gold standard for treating <i>Plasmodium falciparum</i> infections, combining a fast-acting artemisinin derivative with a longer-acting partner drug. However, these oral regimens require multiple doses over several days, which can reduce adherence, compromise parasite clearance, and contribute to the emergence of drug resistance. To overcome these limitations, we developed, for the first time, dissolving microarray patches (MAPs) for the transdermal delivery of amodiaquine and artesunate. Given the different Biopharmaceutics Classification System (BCS) properties of these drugs, amodiaquine (BCS Class III) and artesunate (BCS Class II), Tween® 80 was incorporated to enhance solubility and skin permeability. <i>In vitro</i> release studies demonstrated efficient delivery, with up to 40 % amodiaquine and 90 % artesunate deposited and permeated into the skin. Pharmacokinetic analysis revealed that MAP delivery extended the half-life of artesunate by 8.5-fold (54.05 <i>vs.</i> 6.37 h) and increased its C_max by 21 % (1796.02 ± 154.50 <i>vs.</i> 1421.93 ± 209.61 ng/mL), while amodiaquine's half-life was prolonged by ∼1.4-fold (57.72 ± 19.16 <i>vs.</i> 40.75 ± 7.44 h). In a <i>Plasmodium berghei</i>-infected murine model, the combined MAP treatment reduced parasitaemia by 99.5 % within seven days, showing comparable efficacy to oral administration. These findings demonstrate that dissolving MAPs offer a minimally invasive, needle-free strategy for ACT delivery, with potential to enhance treatment adherence, reduce gastrointestinal side effects, and combat drug resistance, particularly in resource-limited malaria-endemic settings.