Multiple Functions of D-α-Tocopherol Polyethylene Glycol 1000 Succinate (TPGS) as Curcumin Nanoparticle Stabilizer: In Vivo Kinetic Profile and Anti-Ulcerative Colitis Analysis in Animal Model

Heni Rachmawati; Aditya Trias Pradana; Dewi Safitri; I Ketut Adnyana

doi:10.3390/pharmaceutics9030024

Multiple Functions of D-α-Tocopherol Polyethylene Glycol 1000 Succinate (TPGS) as Curcumin Nanoparticle Stabilizer: In Vivo Kinetic Profile and Anti-Ulcerative Colitis Analysis in Animal Model

Pharmaceutics. 2017 Jul 21;9(3):24. doi: 10.3390/pharmaceutics9030024.

Authors

Heni Rachmawati^{1

2}, Aditya Trias Pradana³, Dewi Safitri⁴, I Ketut Adnyana⁵

Affiliations

¹ School of Pharmacy, Bandung Institute of Technology, Ganesha 10, Bandung 40132, Indonesia. h_rachmawati@fa.itb.ac.id.
² Research Center for Nanosciences and Nanotechnology, Bandung Institute of Technology, Ganesha 10 Bandung 40132, Indonesia. h_rachmawati@fa.itb.ac.id.
³ Department of Pharmacy, University of Surabaya, Kalirungkut Raya, Surabaya 60293, Indonesia. Aditya_trias@staff.ubaya.ac.id.
⁴ School of Pharmacy, Bandung Institute of Technology, Ganesha 10, Bandung 40132, Indonesia. dewi.s@fa.itb.ac.id.
⁵ School of Pharmacy, Bandung Institute of Technology, Ganesha 10, Bandung 40132, Indonesia. ketut@fa.itb.ac.id.

Abstract

This study was conducted to evaluate the potential benefit of particle reduction down to nanoscale on curcumin, a unique natural active compound facing therapeutic problems due to low solubility and permeability. In addition, the presence of TPGS as a surfactant for multiple functions on curcumin nanoparticle was addressed. Observation was focused on bioavailability enhancement after oral administration and local anti-inflammatory improvement after rectal dosing. Nanonization of curcumin was performed using an up-scalable top down method. Specific animal models were used to study the in vivo kinetic profile and the biological activity of curcumin nanoparticle, compared with curcumin powder. d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticle was prepared through homogenization with high pressure of the 1500 bar. An in vivo study was performed after oral administration of the preparations to male healthy Wistar rats, to monitor the plasma kinetic profile of curcumin. The biological activity study was conducted after rectal administration of the preparations in Wistar rats induced by 2,4,6-trinitrobenzene sulfonic acid to develop ulcerative colitis. The curcumin nanoparticle with a size of approximately 200 nm was successfully produced and revealed a better in vivo kinetic profile over the larger size of curcumin mixed with TPGS, with bioavailability (AUC_0-∞) that was accounted for seven-fold. In addition, the TPGS-stabilized curcumin nanoparticle demonstrated a superior local anti-inflammatory effect in ulcerative colitis, indicated by the shifting of observed parameters close to the healthy status. The tremendously improved anti-inflammatory effect of the TPGS-stabilized curcumin nanoparticle was found with a very low dose. Reducing the particle size of curcumin down to ~200 nm with the presence of TPGS seems to be a promising approach to improving the therapeutic value of curcumin.

Keywords: Biopharmaceutical class system (BCS); curcumin; d-α-tocopherol polyethylene glycol 1000 succinate (TPGS); high pressure homogenization; in vivo kinetic; nanoparticle; ulcerative colitis.