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. 2014;31(5):501-7.
doi: 10.3109/02652048.2013.879932. Epub 2014 Mar 24.

Evaluation of anticancer activity of celastrol liposomes in prostate cancer cells

Joy Wolfram  1 , Krishna Suri, Yi Huang, Roberto Molinaro, Carlotta Borsoi, Bronwyn Scott, Kathryn Boom, Donatella Paolino, Massimo Fresta, Jianghua Wang, Mauro Ferrari, Christian Celia, Haifa Shen
Affiliations

Evaluation of anticancer activity of celastrol liposomes in prostate cancer cells

Joy Wolfram et al. J Microencapsul. 2014.

Abstract

Context: Celastrol, a natural compound derived from the herb Tripterygium wilfordii, is known to have anticancer activity, but is not soluble in water.

Objective: Formation of celastrol liposomes, to avoid the use of toxic solubilising agents.

Materials and methods: Two different formulations of PEGylated celastrol liposomes were fabricated. Liposomal characteristics and serum stability were determined using dynamic light scattering. Drug entrapment efficacy and drug release were measured spectrophotometrically. Cellular internalisation and anticancer activity was measured in prostate cancer cells.

Results: Liposomal celastrol displayed efficient serum stability, cellular internalisation and anticancer activity, comparable to that of the free drug reconstituted in dimethyl sulfoxide.

Discussion and conclusion: Liposomal celastrol can decrease the viability of prostate cancer cells, while eliminating the need for toxic solubilising agents.

Keywords: Celastrol; liposomes; prostate cancer.

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Conflict of interest statement

Conflict of interest

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Size and polydispersity index (PDI) of liposomes
Liposomes consisted of pegylated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol/celastrol and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol/celastrol. The size (A, C) and PDI (B, D) of liposomes after 0 days (A, B) and 14 days (C, D). The measurements were taken in duplicate (10 runs for each measurement). The data is presented as the mean±SD. Error bars, if not shown, are located within the symbols.
Figure 2
Figure 2. Zeta potential values and electrophoresis mobility of liposomes
Liposomes consisted of pegylated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol/celastrol and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol/celastrol liposomes. The zeta potential (A, C) and electrophoretic mobility (B, D) of liposomes after 0 days (A, B) and 14 days (C, D). The measurements were taken in duplicate (10 runs for each measurement). The data is presented as the mean±SD.
Figure 3
Figure 3. Drug entrapment efficiency of liposomes
Liposomes consisted of pegylated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol/celastrol and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol/celastrol liposomes. The data is presented as the mean±SD. **P ≤ 0.01.
Figure 4
Figure 4. Liposomal stability in 70% fetal bovine serum (FBS)
The size (A) and polydispersity index (PDI) (B) where measured at different time points.
Figure 5
Figure 5. Cumulative drug release of liposomes
Liposomes consisted of pegylated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol/celastrol and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol/celastrol. The drug release was measured in a water/ethanol solution (4:1 v/v) (A) and a serum/PBS (7:3 v/v) solution (B). Measurements were done in triplicate. The data is presented as the mean±SD. Error bars, if not shown, are located within the symbols. *P ≤ 0.05.
Figure 6
Figure 6. Cell viability of VCaP prostate cancer cells
(A) Free celastrol. (B) Liposomal celastrol. Measurements were done in triplicate. The data is presented as the mean±SD. Error bars, if not shown, are located within the symbols.
Figure 7
Figure 7. Intracellular accumulation of free celastrol and liposomal celastrol in VCaP prostate cancer cells
Measurements were done in triplicate. The data is presented as the mean±SD.
See this image and copyright information in PMC

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