Synergistic Effects of Doxorubicin Plga Nanoparticles and Simvastatin Loaded in Silk Films for Local Treatment of Breast Cancer Publisher



Rakhshani A^{1, 2} ; Maghsoudian S^{1, 2} ; Motasadizadeh H³ ; Fatahi Y^{1, 2} ; Malekkhatabi A⁴ ; Ghahremani MH⁵ ; Atyabi F^{1, 2} ; Dinarvand R^{1, 2, 6} Show Affiliations
Source: Journal of Drug Delivery Science and Technology Published:2025

Abstract

An encouraging strategy to address challenges in breast cancer treatment is local drug delivery, targeting the primary tumor site to minimize side effects and drug resistance. Combination therapy, which uses multiple drugs, is effective in reducing drug doses and preventing cancer recurrence. In this study, a pH-responsive silk film containing doxorubicin loaded PLGA nanoparticles and simvastatin (SV/DOX PLGA/SF) to prevent local-regional recurrence, was developed. The DOX PLGA nanoparticles were synthesized in a microfluidic reactor by adjusting the flow rate and polymer concentrations. After optimization, these nanoparticles exhibited uniform size and spherical morphology (168 nm and PDI: 0.096) using concentrations of 0.5 % PLGA and 1 % PVA, and a flow rate of 1 mL/h. The degradation of SF by crosslinking for 7.5 min using methanol was found to occur over approximately 75 days. The release of DOX from DOX PLGA/SF was pH-dependent, with cumulative release on day 11 at pH 5.5 being 74.23 % and at pH 7.4 being 58.91 %. MTT results revealed a synergistic effect of SV and DOX, particularly notable at concentrations of 35 μM SV and 4 μM DOX after 24 h. SV/DOX PLGA/SF films demonstrated the highest tumor suppression effect and the lowest tumor recurrence in female Balb/c mice, with only around 52 ± 10.3 % of the initial tumor. Additionally, histopathological analysis using H&E staining indicated that SF-based localized treatments significantly reduced the mitotic index. © 2024 Elsevier B.V.