Formulation and evaluation of hydrogel-forming microarray patches for transdermal primaquine and chloroquine delivery in malaria therapy

Malaria is still major concern in global health. The standard treatment for malaria involves a combination of chloroquine (CQ), which targets blood-stage parasites, and primaquine (PQ), which eliminates hepatic hypnozoites to prevent relapses. However, these drugs present limitations, including poor adherence due to frequent oral dosing and gastrointestinal side effects. To address these challenges, this study successfully developed, optimised, and characterised lyophilised reservoirs loaded with PQ and CQ, which were incorporated into hydrogel-forming microarray patches (MAPs) for improved malaria treatment. Using a Design of Experiments (DoE) approach, the optimised lyophilised reservoirs dissolved rapidly, within 7 s for CQ and 16 s for PQ. In vitro permeation studies using dermatomed neonatal porcine skin demonstrated efficient drug delivery of approximately 40 mg (70 % delivery efficiency) of each drug over 24 h. Pharmacokinetic analysis in rats showed that MAP administration significantly increased Cmax values from 0.68 ng/mL to 1.68 ng/mL for CQ, and from 14.32 ng/mL to 47.20 ng/mL for PQ compared to oral delivery. Moreover, the area under the curve (AUC0-72h) for the MAP group was 4.4-fold higher for CQ and 1.3-fold higher for PQ compared to oral administration. Efficacy studies in a murine malaria model demonstrated that MAP-delivered PQ and CQ reduced parasitaemia by 99.8 % in treated animals. These findings highlight the potential of MAP technology as a minimally-invasive, sustained drug delivery platform for malaria treatment, potentially offering improved patient adherence, reduced hepatoxicity, and enhanced therapeutic outcomes.