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

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Anjani, Qonita Kurnia ; Volpe-Zanuto, Fabiana ; Miatmoko, Andang ; Moreno-Castellanos, Natalia ; Novais, Janaina Tenorio ; Hariawan, Berlian Sarasitha ; Cahyani, Devy Maulidya ; Octavia, Rifda Tarimi ; Mubarok, Ahmad Shahrul ; Setyaningsih, Wiwit Ananda Wahyu ; Johnston, Callum ; Bargieri, Daniel Y. ; Donnelly, Ryan F.
Número total de Autores: 13
Tipo de documento: Artigo Científico
Fonte: MATERIALS TODAY BIO; v. 35, p. 17-pg., 2025-12-01.
Resumo

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 Plasmodium falciparum 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 (R) 80 was incorporated to enhance solubility and skin permeability. In vitro 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 vs. 6.37 h) and increased its C-max by 21 % (1796.02 +/- 154.50 vs. 1421.93 +/- 209.61 ng/mL), while amodiaquine's half-life was prolonged by similar to 1.4-fold (57.72 +/- 19.16 vs. 40.75 +/- 7.44 h). In a Plasmodium berghei-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. (AU)

Processo FAPESP: 21/06769-0 - Descoberta de alvos vacinais e compostos contra transmissão da Malária
Beneficiário:Daniel Youssef Bargieri
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
Processo FAPESP: 24/17121-0 - Caracterização da proteína CSS com alvo vacinal em esporozoítos de Plasmodium
Beneficiário:Xiomara Alexandra Gaitán
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 23/00431-3 - Caracterização da proteína codificada pelo gene PBANKA_1459100 como um receptor de ativação da gametogênese em Plasmodium
Beneficiário:Janaína Tenorio Novais
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto