Nanoencapsulation of saffron crocin into chitosan/alginate interpolyelectrolyte complexes for oral delivery: A Taguchi approach to design optimization

Crocin, as a nutraceutical component of saffron (Crocus sativus L.), possesses numerous therapeutic effects. In the current study, a crocin-loaded chitosan/alginate (CS/ALG) nanocarrier was developed for oral delivery. The influence of preparation variables including pH and the concentrations of CS, ALG, and calcium chloride (CaCl2 ) on encapsulation efficiency (EE%) and loading efficiency (LE%) of CS/ALG nanoparticles (NPs) was evaluated by L9 Taguchi orthogonal array (OA). The results showed that at 0.25% w/v CS, 0.1% w/v ALG, pH 4.5, and absence of CaCl2 , crocin was loaded into CS/ALG NPs with EE% and LE% of 91.5% and 27.4%, respectively. Ultrasonication reduced the particle sizes (PSs) up to 100 nm, and freeze-dried NPs reproduced the particles with average size of 90 nm. Scanning electron microscopy (SEM) was successfully used to characterize the structure and morphology of freeze-dried NPs, confirming very fine NPs having sizes less than 100 nm. Crocin loaded into NPs showed higher stability in simulated gastric pH 2 compared to free crocin (2.1% and 7.5% degradation at 60 min, respectively). Furthermore, a pH-dependent sustained crocin release was observed with faster release at pH 2. Overall, the very small PS along with high encapsulation efficiency and stability can enhance crocin oral bioavailability making CS/ALG nanovehicles promising as an effective delivery system. PRACTICAL APPLICATION: Crocin as a functional component of Saffron is not sufficiently stable in gastrointestinal tract and its absorption is not complete. Chitosan/Alginate nanoparticles can encapsulate it efficiently, protect it and enhance its absorption orally. The availability and simplicity of the materials and equipments employed in current research provide the possibility to industrial scale up of the Crocin nanoparticles.