Mannose-anchored solid lipid nanoparticles loaded with atorvastatin calcium and vinpocetine as targeted therapy for breast cancer

Abstract

Abstract Background This study was aimed to design mannose-conjugated solid lipid nanoparticles (MSLNs) for the targeted delivery of Atorvastatin Calcium (ATS) and Vinpocetine (VIN) to augment its therapeutic efficacy against breast cancer. SLNs were prepared by hot emulsification ultra-probe sonication method and conjugated with mannose. In vitro cell line, in vivo pharmacokinetic and in vivo tumor regression studies were performed for MSLNs. Results MSLNs had an average particle size of 435.4 ± 3 nm with polydispersity index 0.298 ± 0.03 and a zeta potential of − 28.2 ± 1 emv. Entrapment efficiency was found to be 69.17 ± 0.92%, 71.18 ± 0.68% for ATS and VIN, respectively. The IC50 value of MSLNs was 1.46 µg/ml, which is efficient to control the growth of MDA MB231 cells as compared to the individual drugs and combinatorial SLNs. The combination index was found to be 0.7. MSLNs inhibited cell growth via necrosis by promoting to apoptosis through arresting SubG1 phase. The relative bioavailability of ATS and VIN loaded in MSLNs was 1.47 and 5.70, respectively, as compared to the marketed formulation. Maximal tumor volume reduction and higher survival rate was found for the MSLNs group (76.03%, P = 0.0001) as compared to the control group (P = 0.0364), individual drugs SLNs group. Conclusion The results revealed that the MSLNs formulation augmented activity against breast cancer by inhibiting the cell growth. This promising drug delivery reduces the doses for both the drugs and attains minimal dose-associated side effects with synergism by reaching the specific target site, furthermore improving the therapeutic efficacy.

Keywords

• MSLNs
• Conjugated
• Cell line
• Cell cycle analysis
• In vivo tumor regression