Construction and characterization of thiolated chitosan coated TPGSylated nanodiamonds for oral delivery of curcumin.

Abstract

Low water solubility and poor intestinal permeability hinder the oral absorption of curcumin (CUR). To address this, we designed a core-shell structured nanoparticle based on nanodiamonds (NDs) and thiolated chitosan (TCS). First, D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) covalently modified NDs were prepared and loaded with CUR (CUR@NDs-TPGS). N-acetylcysteine (NAC) was then coupled to chitosan (CS) to obtain positively charged CS-NAC, which electrostatically coated the negatively charged NDs-TPGS/CUR. Particle size (PS), zeta potential (ZP) and drug loading efficiency (DLE) were selected as screening indices to optimize the formulation and preparation process of CUR@NDs-TPGS/CS-NAC via single-factor experiments. The results showed that after coating with CS-NAC, the PS of optimized CUR@NDs-TPGS/CS-NAC increased from 183.63±5.24 nm to 245.24±3.95 nm, the ZP value flipped from -25.47±1.36 to +25.81±1.06 and the DLE value decreased slightly. Moreover, the nanoparticles adopted a spherical morphology and the cumulative release percentage of the nanocomplexes within 24 h decreased from 35.69% to 25.54% after coating. CUR@NDs-TPGS/CS-NAC remained stable within 48 h in simulated intestinal fluid. Mucin adsorption, GI retention and oral absorption of CUR@NDs-TPGS/CS-NAC were further enhanced compared to CUR@NDs-TPGS. These findings suggest that CUR@NDs-TPGS/CS-NAC is a promising carrier for oral delivery of CUR.