Hakeem Memon A.Memon O.Rahman A.U.Khan M.Lashari H.M.Suheryani I.Esa M.Khalil A.A.K.Jahan S.Mahidol University2026-03-282026-03-282026-01-01Drug Development and Industrial Pharmacy (2026)03639045https://repository.li.mahidol.ac.th/handle/123456789/115858Objective: This study aimed to leverage nano-liposomes (NLs) for optimizing the solubility, bioavailability, and pharmacokinetic profiles of 7-hydroxy-5-methoxy-6,8-dimethyl flavanone (7-HMDF), 5,7-dihydroxy-6,8-dimethyl-flavanone (HMF), 2,4-dihydroxy-6-methoxy- 3,5-dimethylchalcone (DMC), betulinic acid (BA), and ursolic acid (UA) derived from the standardized ethanol extract (EE) and supercritical fluid extract (SFE) of Syzygium campanulatum Korth leaves. Significance: This study provides a comprehensive/validated approach for the nano-pharmaceutical development of poorly bioavailable phytomedicines. Methods: NLs encapsulating BA, DMC, EE, and SFE were prepared (thin-film hydration method), optimized, and subsequently characterized. Besides, 6-months stability test, NL-EE and NL-SFE also underwent oral pharmacokinetic evaluation using Sprague-Dawley (SD) rats. Results: HPLC analysis revealed higher concentration of marker compounds within SFE as compared to EE and in silico ADME-Tox profiling predicted safe and favourable pharmacokinetics of those marker compounds. Additionally, NLs demonstrated optimum size (70 238nm), polydispersity index (0.250.43), zeta potential (-28 to -49 mV), encapsulation efficiency (4065%), in vitro drug release, and six months stability. Shelf-life was temperature-dependent, with BA stable at 25°C and DMC moderately stable, but both declined sharply at 60 °C. NLs encapsulation noticeably increased the aqueous solubility of the marker compounds by 50%. Finally, in vivo pharmacokinetic evaluation confirmed the presence of 7-HMDF, HMF, and DMC in rats’ plasma, indicating improved absorption, prolonged circulation, enhanced bioavailability, and sustained release of NLs as compared to their non-liposomal counterparts (EE/SFE). Conclusions: NL encapsulation significantly enhanced the solubility, entrapment efficiency, oral bioavailability, and pharmacokinetic profiles of 7-HMDF, HMF, and DMC from S. campanulatum extracts, demonstrating NLs as promising drug delivery systems.Pharmacology, Toxicology and PharmaceuticsChemistryArticleSCOPUS10.1080/03639045.2026.26316662-s2.0-1050328169321520576241725405