QbD-employed formulation and characterization of sacubitril-loaded solid lipid nanoparticles: a step forward in nanotechnology-based delivery for hypertension.

OBJECTIVE

To develop and characterize sacubitril-loaded solid lipid nanoparticles (SLNs) using a QbD approach to enhance stability, bioavailability, and therapeutic efficacy for improved hypertension management.

METHODS

SAC-loaded SLNs were formulated using a central composite quadratic model within the QbD framework. Characterization techniques, including transmission electron microscopy, differential scanning calorimetry, and Fourier-transform infrared spectroscopy, confirmed particle morphology, crystallinity, and structural integrity. The in vitro antihypertensive activity was evaluated using human aortic smooth muscle cells (HASMCs) via MTT assay, assessing cell viability and inhibition rates. A novel reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed for quality control, utilizing a C18 column with a methanol (80:20 v/v) mobile phase.

RESULTS

The optimized formulation exhibited particle size of 184 nm, zeta potential of -28 mV, high entrapment efficiency (93.83%), and sustained drug release (86.23% over 24 h). In vitro studies demonstrated the significant efficacy of SAC-loaded SLNs in inhibiting hypertension-induced HASMCs, achieving a 61.97% inhibition rate. Comparative analysis showed the superior performance of SAC-SLNs over standard SAC, highlighting their potential as an advanced treatment option in cardiovascular care The RP-HPLC method showed excellent sensitivity (LOD of 0.96 µg/mL; LOQ of 2.93 µg/mL), linearity (R2 = 0.998), ensuring robust quality control.

CONCLUSION

SLNs are a promising platform for enhancing SAC delivery and improving cardiovascular outcomes, addressing the limitations of traditional formulations to advance drug therapy in critical healthcare.