Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles

Wenrui Wang,^1,* Rongrong Zhu,^1,* Qian Xie,¹ Ang Li,¹ Yu Xiao,¹ Kun Li,¹ Hui Liu,² Daxiang Cui,³ Yihan Chen,¹ Shilong Wang<sup>1

1</sup>East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China; ²Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China; ³National Key Laboratory of Nano/Micro Fabrication Technology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

^*These authors contributed equally to this study

Abstract: Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of -20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy.

Keywords: airway hyperresponsiveness, pharmacokinetics, curcumin, solid lipid nanoparticles