Design of experiments-based optimization of rutin-loaded nanostructured lipid carriers: characterization, pharmacokinetics, and stability evaluation

Due to their minimal toxicity, herbal agents have recently gained preference as therapeutic options for various diseases. However, their clinical efficacy is often restricted due to their physicochemical limitations such as poor aqueous solubility, low bioavailability, and short half-life. This study aimed to develop rutin-loaded nanostructured lipid carriers (Rt-NLCs) to enhance solubility and therapeutic potential. Rt-NLCs were formulated using a high-speed homogenization-ultrasonication technique and optimized through a 3-factorial (3(3)) Box-Behnken design (BBD). The optimized Rt-NLCs exhibited a particle size (PS) of 172.8 +/- 3.10 nm, a polydispersity index (PDI) of 0.32 +/- 0.20, a zeta potential (ZP) of -27.2 +/- 2.10 mV, and a % entrapment efficiency (EE) of 79 +/- 4.31%. The formulation demonstrated sustained drug release (82.12% +/- 6.2%) over 30 h compared to a rutin suspension. Transmission electron microscopy (TEM) analysis confirmed that the particles were spherical, smooth-surfaced, and nanosized. Additionally, Rt-NLCs exhibited excellent stability, ensuring an optimal shelf-life. Pharmacokinetic studies revealed a significant increase in bioavailability following intraperitoneal administration of Rt-NLCs compared to the rutin suspension. The findings support the potential of NLC-based encapsulation as a viable method to improve rutin's therapeutic properties.