Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics

Abstract

This study aimed to investigate the in vitro skin permeation and in vivo antineoplastic effect of curcumin by using liposomes as the transdermal drug-delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and hydrogenated soybean phospholipids (HSPC) were selected for the preparation of different kinds of phospholipids composed of curcumin-loaded liposomes: C-SPC-L (curcumin-loaded SPC liposomes), C-EPC-L (curcumin-loaded EPC liposomes), and C-HSPC-L (curcumin-loaded HSPC liposomes). The physical properties of different lipsomes were investigated as follows: photon correlation spectroscopy revealed that the average particle sizes of the three types of curcumin-loaded liposomes were 82.37 ± 2.19 nm (C-SPC-L), 83.13 ± 4.89 nm (C-EPC-L), and 92.42 ± 4.56 nm (C-HSPC-L), respectively. The encapsulation efficiency values were found to be 82.32 ± 3.91%, 81.59 ± 2.38%, and 80.77 ± 4.12%, respectively. An in vitro skin penetration study indicated that C-SPC-L most significantly promoted drug permeation and deposition followed by C-EPC-L, C-HSPC-L, and curcumin solution. Moreover, C-SPC-L displayed the greatest ability of all loaded liposomes to inhibit the growth of B16BL6 melanoma cells. Therefore, the C-SPC-L were chosen for further pharmacodynamic evaluation. A significant effect on antimelanoma activity was observed with C-SPC-L, as compared to treatment with curcumin solution in vivo. These results suggest that C-SPC-L would be a promising transdermal carrier for curcumin in cancer treatment.

Figure 1

Chemical structure of curcumin.

Figure 2

Morphology of curcumin-loaded liposomes. (A) C-SPC-L; (B) C-EPC-L; and (C) C-HSPC-L. Scale length: 200 nm; (D) C-SPC-L (2 months later); (E) C-EPC-L (2 months later); and (F) C-HSPC-L (2 months later). Scale length: 100 nm.

Figure 3

Heating curves of DSC for curcumin, physical mixture with or without curcumin, and liposomes systems: Physical mixtures I: physical mixture without curcumin; physical mixtures II: physical mixture with curcumin. A: Curcumin; B: Physical mixtures I(SPC); C: Physical mixtures II(SPC); D: C-SPC-L; E: Physical mixtures I(EPC); F: Physical mixtures II(EPC); G: C-EPC-L; H: Physical mixtures I(HSPC); I: Physical mixtures II(HSPC); J: C-HSPC-L.

Figure 4

Release percentage (%) of curcumin from the C-SPC-L, S-EPC-L, and C-HSPC-L systems. Each value is represented as the mean ± S.D. (n = 3).

Figure 5

Effects of the phospholipids on curcumin permeated through excised rat skin. (mean ± SD, n = 3).

Figure 6

Effects of phospholipids on curcumin retained in the excised rat skin (mean ± SD, n = 3) * p < 0.05 versus curcumin group.

Figure 7

Growth-inhibiting effect of curcumin on B16BL6 cells. The results are expressed as percentage of cell-inhibition rate as compared to untreated, control cells. Data are represented as mean ± S.D. (n = 3). * p < 0.05 versus curcumin solution group.

Figure 8

Curcumin-loaded liposomes inhibit tumor growth in vivo. Tumors excised from C57BL/6 mice are exhibited in (A). a: blank control group; b: vehicle(drug-free liposome carbomer hydrogel); c: 20 mg·kg⁻¹ curcumin solution in 1% carbomer hydrogel; d: 20 mg·kg⁻¹ C-SPC-L in 1% carbomer hydrogel, a-d are transdermally administered every day; e: 20 mg·kg⁻¹ cyclophosphamide by intraperitoneal injection. Tumor weight and inhibition rates accounting for tumor weight are shown in (B) and (C). * p < 0.05 versus control group, + p < 0.05 versus vehicle group.