Enhanced delivery of podophyllotoxin for hepatocellular carcinoma therapy using polymersome as an anticancer delivery platform

Podophyllotoxin (PPT), a bioactive compound, shows promise as a potential cancer treatment drug. Nevertheless, low solubility and bioavailability of PPT necessitate a drug delivery system to improve its effectiveness. PPT was extracted from Linum album and delivered into HepG2 cancer cells using mPEG-PCL nanoparticles. Copolymers were synthesized and confirmed by UV–Vis, FTIR, ¹HNMR, XRD, FESEM analyses, and the other physicochemical properties were also characterized. The critical micelle concentration of the copolymers was calculated, and the ratio of 1:10 with a CMC of 0.055 µg. mL⁻¹ was selected as the optimal ratio. The average size and surface charge of micelles were 186 ± 12 nm and −5.13 ± 0.61 mV, respectively. FESEM analysis showed a uniform and spherical structure of nanoparticles. PPT was loaded into mPEG-PCL micelles in various ratios (w/w) of drug: copolymer using the nanoprecipitation method, and the ratio of 1:1 was selected as the optimal ratio with encapsulation and loading efficiency of 79.89 ± 1.28% and 10.15 ± 2.16%, respectively. The PPT release profile demonstrated a significant difference between the sustained release of PPT from the nanoparticles and the rapid release of free PPT. Cellular uptake studies revealed that the polymersomes effectively deliver the PPT to the HepG2 cells. The <i>in vitro</i> cytotoxicity assay showed increased cytotoxicity of PPT/mPEG-PCL NPs compared to the free drug. Based on the overall results, these nanoparticles show promise as a delivery system for controlled release of PPT in cancer therapy. A pH-sensitive mPEG-PCL nanoparticles for delivery of podophyllotoxin was prepared.mPEG-PCL nanoparticles enhance PPT bioavailability and efficacy for liver cancer treatment.Controlled release of PPT from nanoparticles improves therapeutic efficacy compared to free drug.mPEG-PCL micelles can effectively deliver PPT into HepG2 cancer cells.PPT-loaded mPEG-PCL nanoparticles enhance drug delivery and cytotoxicity against HepG2 cancer cells. A pH-sensitive mPEG-PCL nanoparticles for delivery of podophyllotoxin was prepared. mPEG-PCL nanoparticles enhance PPT bioavailability and efficacy for liver cancer treatment. Controlled release of PPT from nanoparticles improves therapeutic efficacy compared to free drug. mPEG-PCL micelles can effectively deliver PPT into HepG2 cancer cells. PPT-loaded mPEG-PCL nanoparticles enhance drug delivery and cytotoxicity against HepG2 cancer cells.