Design of Hybrid Polymeric-Lipid Nanoparticles Using Curcumin as a Model: Preparation, Characterization, and In Vitro Evaluation of Demethoxycurcumin and Bisdemethoxycurcumin-Loaded Nanoparticles

Abstract

Polymeric lipid hybrid nanoparticles (PLHNs) are the new generation of drug delivery systems that has emerged as a combination of a polymeric core and lipid shell. We designed and optimized a simple method for the preparation of Pluronic F-127-based PLHNs able to load separately demethoxycurcumin (DMC) and bisdemethoycurcumin (BDM). CUR was used as a model compound due to its greater availability from turmeric and its structure similarity with DMC and BDM. The developed method produced DMC and BDM-loaded PLHNs with a size average of 75.55 ± 0.51 and 15.13 ± 0.014 nm for DMC and BDM, respectively. An FT-IR analysis confirmed the encapsulation and TEM images showed their spherical shape. Both formulations achieved an encapsulation efficiency ≥ 92% and an exhibited significantly increased release from the PLHN compared with free compounds in water. The antioxidant activity was enhanced as well, in agreement with the improvement in water dissolution; obtaining IC₅₀ values of 12.74 ± 0.09 and 16.03 ± 0.55 for DMC and BDM-loaded PLHNs, respectively, while free curcuminoids exhibited considerably lower antioxidant values in an aqueous solution. Hence, the optimized PHLN synthesis method using CUR as a model and then successfully applied to obtain DMC and BDM-loaded PLHNs can be extended to curcuminoids and molecules with a similar backbone structure to improve their bioactivities.

Keywords: Pluronic F-127; bisdemethoxycurcumin; curcumin; demethoxycurcumin; drug delivery; polymer-lipid hybrid nanoparticles.

Figure 1

Schematic representation of PLHNs and chemical structure of Pluronic F-127, CUR, DMC, and BDM.

Figure 2

Schematic representation of the developed and optimized method procedure.

Figure 3

FT–IR spectra of PLHNs main components, CUR–loaded PLHNs and plain PLHNs.

Figure 4

FT–IR spectra of DMC and BDM–loaded PLHNs, plain PLHNs and free DMC and BDM.

Figure 5

TEM images and size distribution histogram of (A) DMC and (B) BDM–loaded PLHNs.

Figure 6

DSC curves of PLHNs main components and the DMC and BDM–loaded formulation.

Figure 7

Release profile of DMC and BDM from the PLHNs compared with free DMC and BDM dissolution rate in two dissolution media. Error bars represent the standard deviation of DMC and BDM concentration in the triplicates.