Development and evaluation of a nanoliposomal hydrogel of Pelargonium graveolens essential oil as a repellent against Anopheles stephensi mosquitoes

Abstract The increasing concern over the dermatological and neurological side effects of synthetic repellents aimed us to develop a stable and efficacious nanoliposomal hydrogel formulation containing Pelargonium graveolens essential oil (EO) and to evaluate its repellent efficacy against the primary urban malaria vector, Anopheles stephensi . Geranium EO was first complexed with β-cyclodextrin (β-CD) to enhance its stability and reduce volatility. This inclusion complex was then encapsulated within nanoliposomes using a microfluidic hydrodynamic focusing (MHF) technique with an optimized aqueous-to-organic FRR, producing unilamellar vesicles with a mean hydrodynamic diameter of 115.4 ± 3.7 nm and a low Polydispersity Index (PDI) of 0.21 ± 0.02, indicating a highly homogeneous vesicle population. The nanoliposomal suspension was subsequently incorporated into a carboxymethyl cellulose (CMC) hydrogel matrix to form a topical formulation. The final nanoliposomal hydrogel demonstrated a high Encapsulation Efficiency (EE%) of 58.7 ± 2.4% for geranium EO and remained physically stable over 6 months under ICH Q1A(R2)-compliant conditions, with no signs of phase separation, syneresis, or pH drift. The repellent efficacy was evaluated against laboratory-reared, unfed female Anopheles stephensi mosquitoes using the World Health Organization (WHO) recommended arm-in-cage method. The optimized nanoliposomal hydrogel containing 2.5% geranium EO provided a complete protection time (CPT) of 285.5 ± 10.3 min against mosquito bites, which was significantly longer ( p < 0.01) than the CPT provided by an equivalent concentration of DEET under identical conditions. Both the placebo CMC hydrogel and blank nanoliposomal hydrogel showed negligible repellency (CPT < 5 min). These results demonstrate that the nanoliposome-hydrogel hybrid system effectively overcomes the inherent volatility and instability limitations of natural EOs, enabling a plant-based repellent to achieve superior and prolonged efficacy compared to the synthetic gold standard DEET. This formulation represents a highly promising for personal protection against malaria and other mosquito-borne diseases, with potential applications in integrated vector management programs, particularly in regions affected by insecticide-resistant Anopheles populations.