Enhanced stability and binding efficiency of liposomal andrographolide complexes targeting human papillomavirus for cervical cancer therapy: Molecular docking and molecular dynamics simulations

Cervical cancer is among the most common causes of cancer-related deaths in women globally, with human papillomavirus (HPV) being the primary factor behind its development. The virus produces two key oncoproteins, E6 and E7, critical in triggering carcinogenesis. Andrographis paniculata (Burm.f.) Nees, a well-known medicinal plant, contains andrographolide, which has shown considerable promise as an anticancer agent. However, its low solubility in water limits its therapeutic application, making it essential to use an effective drug delivery system, such as liposomes. This study investigated the interaction and stability of liposome-encapsulated andrographolide using different coconut-derived phospholipids. Molecular docking and molecular dynamics simulations were performed to assess its binding to the E6 protein of HPV 18B. Docking analysis showed that the PC 10:0_14:0-cholesterol-andrographolide complex had the most favorable binding score of −4.50 kcal/mol, suggesting that liposomal encapsulation is achievable and stable. Among the complexes, E6-LPC 18:1-cholesterol-andrographolide demonstrated the strongest binding affinity, with a score of −6.73 kcal/mol. A 50-ns molecular dynamics simulation further confirmed that this complex had the highest binding energy, while E6-PE 18:1_18:2-cholesterol-andrographolide was the most stable, with an RMSD value of 4.38 Å. Overall, the findings indicate that incorporating andrographolide into a liposomal system greatly improves its stability, binding capability, and interaction with the target protein, highlighting its potential as a promising therapeutic approach for HPV 18B-associated cervical cancer. The andrographolide-liposome complex demonstrated strong binding to E6 HPV 18B, with enhanced stability and interaction strength, highlighting its potential as an effective inhibitory agent. • Encapsulating andrographolide enhanced stability and binding efficiency. • Encapsulating andrographolides in a liposome were feasible and more stable. • Liposome complex PC 10:0_14:0-cholesterol-andrographolide had the best docking value at −4.50 kcal/mol. • Andrographolide exhibited strong binding to E6 HPV 18B (E6-LPC 18:1-cholesterol-andrographolide) with a docking score of −6.73 kcal/mol. • MD simulations confirmed high binding energy, supporting its potential as an effective HPV inhibitor.