Complexes of Pentagamavunon-1 and Lactosylated Albumin for Enhancing the Cytotoxic Effect on Hepatocellular Carcinoma

PGV-1 exhibits potential as an anticancer drug for hepatocellular carcinoma (HCC), and this study focuses on enhancing its solubility and cytotoxicity against liver cancer cells. To achieve this, complexes were developed by combining Bovine Serum Albumin (BSA) with lactose, aiming to improve the bioavailability of PGV-1 as an anticancer agent. Subsequently, these complexes were further modified through lactosylation, resulting in PGV-1-loaded lactosylated BSA (PGV-1+BSA+Lac), with the purpose of increasing their cytotoxic effects on HCC cells. The glycation of BSA with d-lactose was conducted under dry-heat conditions at 60°C for various durations (0, 30, 60, 120, or 240 minutes). Monitoring the extent of BSA glycation involved assessing the availability of free peptide and examining the molecular weight profile. A straightforward formulation was proposed, involving the complexation of BSA lactosylated with PGV-1. The solubility of PGV-1 in aqueous solutions was assessed with varying amounts of BSA. Cytotoxicity was evaluated through an MTT assay using the HLF liver cancer cell line. The results revealed distinct variations in BSA conjugation depending on the duration of heating. Modified BSA exhibited reduced peptide availability and slower migration in SDS/PAGE. Notably, PGV-1 demonstrated significantly higher solubility when combined with BSA+Lac, as compared to PGV-1+BSA. The IC50 values for PGV-1+BSA+Lac in HLF cells (0.008±0.002 µM) were markedly lower than those for PGV-1 (0.437±0.002 µM) and PGV-1+BSA (0.631±0.002 µM), highlighting the potent inhibitory effect of PGV-1+BSA+Lac on HLF cell proliferation. These findings suggest that PGV-1+BSA+Lac complexes hold promise as potential candidates for targeted PGV-1 delivery in HCC therapy