Calycosin-loaded mucoadhesive smart lipids: Next-Generation lipid nanocarriers for enhancing oral drug bioavailability

Calycosin (CYS), a BCS class IV drug, exhibits poor solubility and permeability, leading to poor oral bioavailability. To address this issue, CYS-loaded mucoadhesive smart lipids (MSLs) were developed in this study. Chitosan was grafted with sulfhydryl groups to enhance mucoadhesion and then inserted in smart lipids via hot high-pressure homogenization using stearic acid, myristic acid, palmitic acid, Softisan 142, Dynasan P 116 (solid lipids), Miglyol® 812 (liquid lipid), stearyl alcohol (fatty alcohol), and Tween 80 (surfactant). MSLs were characterized by FTIR and SEM (scanning electron microscopy). Moreover, PDI (polydispersity index), particle size, and zeta potential (ζ) were evaluated via dynamic light scattering (DLS). Furthermore, entrapment efficiency (EE), loading capacity (LC), in vitro drug release, stability testing, safety studies, mucoadhesion, and mucus diffusion studies were performed. Furthermore, a proof-of-concept in vivo study was conducted on Sprague-Dawley rats. The results indicated spherical-shaped nanocarriers with sizes of 149 ± 18 nm, ζ of -35.0 ± 3 mV, and PDI of 0.194 ± 0.01, having EE of 85 ± 3% and LC of 7.8%. The MSLs were found stable at elevated temperatures and showed a sustained drug release pattern. Safety studies reveal that almost 90% of cells remain viable after 24 h. Mucoadhesion studies confirmed 15.6-fold enhanced mucoadhesion for MSLs after 2.5 h that led to less mucus permeation. In vivo analysis demonstrated a 3.89-fold enhanced C_max for drug-loaded MSLs, and 33% relative bioavailability (F_r) was calculated in comparison to 5.8% oral bioavailability of the free drug. Based on all these facts, it is recommended that mucoadhesive smart lipids are ideal lipid-based nanocarriers for the enhancement of oral bioavailability of CYS.