ABSTRACT The study aimed to develop an Aprepitant (APT)‐loaded controlled‐release solid‐lipid nanoparticles (SLN) using a precipitation method with chitosan and thiolated chitosan (TC) to enhance drug solubility and mucoadhesion. The optimized SLN formulation (APT‐TCF4) showed a particle size of 87.28 ± 0.43 nm, a zeta potential of +13.8 ± 0.54, encapsulation efficiency of 93.92 ± 0.87%, and 71.25 ± 0.64% solubility of APT in phosphate buffer (pH 6.8). Scanning electron microscopy (SEM) revealed nanosized, amorphous spherical particles and FTIR analysis confirmed good compatibility between APT and the polymers (chitosan and TC) while, physicochemical evaluation indicated no drug‐polymer interactions. In vitro drug release study demonstrated that APT‐TCF4 exhibited controlled drug release (84.56 ± 0.46%) over 12 h in phosphate buffer (pH 6.8), following the Higuchi release model. Additionally, APT‐TCF4 showed a 26‐fold increase in mucoadhesion compared to APT alone and an 11‐fold increase compared to APT‐CF4. SLN containing TC demonstrated prolonged residence time at intestinal mucosa and reduced toxicity to Caco‐2 cells. In vivo studies demonstrated a significant enhancement in APT bioavailability due to controlled swelling, increased residence time, sustained release and paracellular transportation across the intestine. Conclusively, APT‐TCF4 represents an oral drug delivery system utilizing TC to improve bioavailability and enhance mucoadhesion making it promising approach for the treatment of chemotherapy‐induced nausea and vomiting.
Hussain et al. (Sun,) studied this question.