Telmisartan loaded lipid nanocarrier as a potential repurposing approach to treat glioma: characterization, apoptosis evaluation in U87MG cells, pharmacokinetic and molecular simulation study

• Published in: Nanotechnology 2024-10, Vol.35 (42), p.425101
• Main Authors: Rout, Sagar, Satapathy, Bhabani Sankar, Sahoo, Rudra Narayan, Pattnaik, Snigdha
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Liberation; Drug Repositioning; Glioma - drug therapy; Glioma - metabolism; Glioma - pathology; Humans; lipid nanocarriers; Lipids - chemistry; Male; Molecular Docking Simulation; Nanoparticles - chemistry; pharmacokinetics; Rats; telmisartan; Telmisartan - administration & dosage; Telmisartan - chemistry; Telmisartan - pharmacokinetics; Telmisartan - pharmacology; U87MG cells
• ISSN: 0957-4484; 1361-6528; 1361-6528
• DOI: 10.1088/1361-6528/ad64e0

The study explores anticancer potential of telmisartan (TS) loaded lipid nanocarriers (TLNs) in glioma cells as a potential repurposing nanomodality along with estimation of drug availability at rat brain. Experimental TLNs were produced by previously reported method and characterized. anticancer efficacy of experimental TLNs was estimated by MTT, confocal microscopy, and FACs analysis in glioma cells. Plasma and brain pharmacokinetic (PK) parameters were also analysed by LCMS/MS. Spherical, nanosized, homogenous, unilamellar, TLNs were reported having desirable drug loading (9.5% ± 0.6%), negative zeta potential and sustained TS release tendency. FITC-TLNs were sufficiently internalized into U87MG cells line within 0.5 h incubation period. IC for TLNs was considerably higher than free TS in the tested glioma cell lines. Further, TLNs induced superior apoptotic effect in U87MG cells than TS. PK (plasma/brain) data depicted higher AUC, , MRT with lower Cl for TLNs suggesting improved bioavailability, residence and sustained drug availability than free TS administration. Docking studies rationalized results as preferably higher binding affinity (docking score:12.4) was detected for TS with glioma proteins. Further, studies in glioma bearing xenograft model is underway for futuristic clinical validation of TLNs.