Characterization of behavior of the inclusion complex between Sulfobutylether-β-cyclodextrin loaded alginate/chitosan nanoparticles and indomethacin as a potential approach for drug delivery

Abstract

Indomethacin (IND) is a nonsteroidal anti-inflammatory drug with low aqueous solubility and irritating gastrointestinal side effects. By complexing this drug inside the cavity of cyclodextrin (CD) and loading it into polymer nanoparticles such as Chitosan (CS) and Alginate (Alg), in addition to increasing its solubility, a targeted drug delivery platform can be created to release this drug. In this study, initially, the complex of IND with Sulfobutylether-β-cyclodextrin (SBE-β-CD) was created using the freeze-drying method. Then, by ionic gelation method, the complex was loaded into CS nanoparticles, and finally, these nanoparticles were coated with Alg to enable drug release in the intestinal environment. Complexes and nanoparticles formation were investigated by phase solubility, FTIR, HNMR, XRD, and SEM methods. Moreover, the Zeta potential method was used to measure the stability of nanoparticles coated with Alg. According to phase solubility studies, drug solubility increased linearly with increasing CD concentration, indicating an AL-type system. In addition, according to the phase solubility diagram, the stability constant and complexation efficiency were obtained 177 M−1 and 0.388, respectively. In the following, the formation of chitosan nanoparticles was confirmed through spectral shifts observed in FTIR analysis as well as morphological changes revealed in SEM analysis. Also, the zeta potential of Alg coated nanoparticles was 110.067 mV, which indicates the good stability of these nanoparticles. At the end, in vitro release studies were conducted to investigate the pH-sensitive capability of these nanoparticles at pH = 1.5 and pH = 7. The formed nanosystem successfully released 78.51 % of the drug at pH = 7 and prevented its release in acidic pH.