The Development of a Novel Nanoherbal Passionfruit (Passiflora edulis) Leaves with Safety and Analgesic Effect
Authors: Fahleni Fahleni , Desmiaty Yesi , Dewi Rika Sari , Kholilah Anisah , Izzah Mona Sarvilia Nurul , Sandhiutami Ni Made Dwi 
Published: October 2024

Passionfruit (Passiflora edulis) leaves are proven to contain flavonoids especially quercetin and showed a significant antinociceptive effect at acetic acid-induced wriggling. Modification of passionfruit leaf extract into nanoparticles can provide therapeutic effects precisely, quickly, and optimally. This study aimed to provide the method of preparation, and characterization of nanoherbal passionfruit leaves (NPL) and evaluate its safety profiles and analgesic effect. NPL was synthesized using ionic gelation methods, with 3 formula variations. Passionfruit leaf extract was dissolved using mixed solvents. The passionfruit leaves extract solution was suspended in Chitosan and dripped with sodium tripolyphosphate solution until nanoparticle formation. The characterization of the NPL study was evaluated by measuring the particle size, polydispersity index (PI), zeta potential, entrapment efficiency (EE), drug release, and transmission electron microscope (TEM) images. The safety profiles of NPL were then assessed in mice by acute and subchronic toxicity using OECD methods. The effectiveness of NPL as an analgesic was tested using an acetic acid test (visceral pain) in mice. We found the particle size of the NPL’s best formula (F2-NPL) obtained was 187.6 nm with polydispersity index 0.626 and zeta potential +31.2 mV. The entrapment efficiency of flavonoid content in NPL was 50.9 % and the flavonoid release for 3 h with 3 replications were 22.91, 27.88 and 25.27 % respectively. The morphology of the particles by TEM showed that the nanoparticles were circular shape. Safety evaluation in mice resulted in the LD50 of NPL being greater than 5000 mg/kg in the acute toxicity study and had no adverse effects on blood, liver, and renal profiles in the subchronic toxicity study. The NPL-200 group had better effectiveness as an analgesic (84.87 %) compared to NPL-50 (37.80 %) and NPL-100 (69.15 %). This finding indicates that the NPL is a safe and effective formula for enhancing analgesic effects. Thus, enables its applications for the treatment of various diseases related to analgesics and inflammation such as osteoarthritis.
HIGHLIGHTS

The development of traditional medicine continues to be improved, to obtain the availability of safe, high quality, efficacious traditional medicines that are scientifically tested and can be widely utilized both for self-treatment by the community and in health services
It is known that the most widely reported flavonoid derivative contained in edulis leaves is quercetin. Quercetin has poor bioavailability, solubility, and stability, reducing its therapeutic effect.
By creating nanoparticles, adjustments can be made to natural products including quercetin in flavonoids in order to maximize their activity, boost their bioavailability, solubility, and capacity to be swiftly absorbed in the body to deliver the best possible therapeutic effects
In developing nanoherbal passionfruit leaves using the ionic galation method, several solvents were used. It is known that no chemical substance can be said to be completely safe. It is important to study the toxicity profile further to obtain safe traditional medicines.
Nanoparticle formulation of passion fruit leaf extract can provide better pain inhibition effectiveness in mice

GRAPHICAL ABSTRACT