Preparation and in vivo pharmacokinetics of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles

Runliang Feng,^1,* Zhimei Song,^1,* Guangxi Zhai<sup>2

1</sup>Department of Pharmaceutical Engineering, College of Medicine and Life Science, University of Jinan, Jinan, Shandong Province, ²Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong Province, People's Republic of China

^*These authors contributed equally to this work

Background: Curcumin (CUR) has been linked with antioxidant, anti-inflammatory, antimicrobial, anti amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability.
Methods: To improve its bioavailability and water solubility, we synthesized two series of poly (ε-Caprolactone)-poly (ethylene glycol)-poly (ε-Caprolactone) triblock copolymers by ring-opening polymerization of poly (ethylene glycol) and ε-Caprolactone, with stannous 2-ethylhexanoate as the catalyst. Structure of the copolymers was characterized by proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography. The nanoparticles (NPs) were prepared using a probe-type ultrasonic emulsion and solvent evaporation method. To obtain an optimal delivery system, we explored the effect of the length of the copolymers' hydrophilic and hydrophobic chains on the encapsulation of hydrophobic CUR, performing entrapment efficiency and drug loading evaluations, as well as studying the particle distribution and in vitro release using the direct dispersion method. Finally, study of the in vivo pharmacokinetics of the CUR-loaded NPs was also carried out on selected copolymers in comparison with CUR solution formulations.
Results: CUR was encapsulated with 94.3% and 95.5% efficiency in biodegradable nanoparticulate formulations based on NP43 and NP63, respectively. Dynamic laser light scattering and transmission electron microscopy indicated a particle diameter of 55.6 nm and 62.4 nm for NP43 and NP63, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry analysis of the NPs showed that CUR was encapsulated into the NPs. The in vitro release experiments showed that NP63 controlled the release of CUR more effectively, with only 55% of CUR released after 96 hours. In comparison with the free-drug solution in vivo, encapsulation of the CUR in NP63 increased mean residence time from 0.169 to 40.148 hours and the area under the concentration–time curve 4.178-fold.
Conclusion: CUR was effectively entrapped by the prepared NPs, which could improve the solubility of CUR and prolong its retention in the systemic circulation.

Keywords: nanoparticle, copolymer, solubility, hydrophilic chain, hydrophobic chain