Development and characterization of lecithin-based self-assembly mixed micellar drug delivery systems for curcumin

Abstract

Event Abstract Back to Event Development and characterization of lecithin-based self-assembly mixed micellar drug delivery systems for curcumin Ling-Chun Chen1*, Yin-Chen Chen1, Chia-Yu Su1, Wan-Ping Wong1, Ming-Thau Sheu1* and Hsiu-O Ho1 1 Taipei Medical University, College of Pharmacy, Taiwan Curcumin is the active ingredient extracted from the root of Curcuma longa. However, the great therapeutic applications of curcumin are restricted because of its low aqueous solubility, rapid hydrolysis in alkaline media, light instability and hydrophobic character, resulting in poor bioavailability (BA) (only 1% in rats). Mixed polymeric micelle (MPM), which is able to increase the volume of the hydrophobic core by incorporating extra hydrophobic materials providing larger space for hydrophobic drugs to be solubilized, was developed to overcome major obstacles associated with curcumin delivery. Lecithin is a biocompatible surfactant which is an important component of cell membrane and makes drug easily absorbed, and an additional amphiphilic polymer (sodium dedoxycholate (NaDOC), d-alpha tocopheryl polyethylene glycol succinate (TPGS), Cremophor® and Pluronic® series) were added to form MPM. Curcumin-MPM was prepared by thin film method. Briefly, a predetermined ratio of curcumin, lecithin and another polymer (NaDOC, Pluronic® series of F87, F127, F68, L121, F108, and P123, TPGS, and Cremophor® RH40 and ELP) were added into 1 mL of mixed solvent (Methanol/dichloromethane=3/7, v/v) in the round bottom flask. The mixture was shaken and subsequently evaporated by rotary evaporation under reduced pressure to remove solvent and obtain a thin film. Self-assembly of the thin films resulting in micelle formation was formed by adding 1 mL of deionized water and shook the micelle solution gently until the thin film was completely dispersed. Self-assembling curcumin-MPM was evaluated to determine characteristics such as the average particle size and size distribution, encapsulation efficacy [EE] and drug loading [DL]. After formulation optimization, the formulations were curcumin/ lecithin/ NaDOC= 2/1/5 and curcumin/lecithin/Pluronic® P123=5/2/20, with particle size of less than 200 nm, EE of >80%, and DL of >10%. The formulated system efficiently improved the stability of curcumin in PBS at room temperature or 4 ℃, and in FBS or PBS at 37℃, and retarded in vitro curcumin release. In vivo PK studies shows for oral administration, the absolute BA was 3- and 5-fold increased for curcumin-loaded NaDOC and Pluronic® P123 MPM, respectively; for intravenous administration, the absolute BA was 2.32- and 5.73-fold improvement for curcumin-loaded NaDOC MPM and Pluronic® P123 MPM, respectively.Whereas, for native curcumin solution, the level was not detected beyond 24 h and 2 h with oral and intravenous administration. Our results suggested the slow release of curcumin from micelles, reduced degradation, and prolonged duration resulted in the increase of BA in rats regardless of oral or intravenous administration. In conclusion, lecithin-based MPM represented a useful curcumin delivery system, thereby improving the solubility, stability and BA of curcumin. The enhancement of curcumin BA via lecithin-based MPM can bring this natural molecule to the forefront of therapeutic agents which can treat dreadful cancer. Figure1. Plasma concentration-time curves of curcumin after intravenous administration of lecithin-based mixed micelles (NaDOC and Pluronic® P123) and free curcumin (5 mg/kg) to rats. Figure2. Plasma concentration-time curves of curcumin after oral administration of lecithin-based mixed micelles (NaDOC and Pluronic® P123) and free curcumin (100 mg/kg) to rats. NSC 102-2320-B-038 -022 -MY3