Curcumin formulated in solid lipid nanoparticles has enhanced efficacy in Hodgkin's lymphoma in mice

Abstract

Curcumin reduces Hodgkin's lymphoma (HL) cell growth in vitro, but its unfavorable pharmacokinetics highlight the need for novel in vivo delivery systems. Thus, we explored whether formulation of curcumin in solid lipid nanoparticles (SLN-curc) or d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (TPGS-curc) could enhance its efficacy in mice. Curcumin formulated in SLN and in TPGS resulted in higher curcumin plasma levels in mice. Compared to vehicle-treated controls, SLN-curc and TPGS-curc reduced HL xenograft growth by 50.5% (p < 0.02) and 43.0% (p < 0.04), respectively, while curcumin reduced it by 35.8% (p < 0.05). In addition, SLN-curc reduced the expression of proteins involved in cell proliferation and apoptosis (XIAP and Mcl-1) in HL tumor extracts. In HL cells in culture, curcumin decreased the expression of relevant anti-inflammatory cytokines (IL-6 and TNF-α) in a concentration-dependent manner. Moreover, when given in combination with bleomycin, doxorubicin and vinblastine, curcumin showed an additive growth inhibitory effect. In conclusion, SLNs appear as an appropriate and effective drug delivery system for curcumin. Given the efficacy of SLN-curc and the enhanced growth inhibitory effect when combined with chemotherapeutic drugs, we speculate that curcumin, when appropriately formulated, is a promising adjuvant agent for the treatment of HL and merits further evaluation.

Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication

“…To enhance targeting capability and solid-tumor penetration, Legumain-targeting strategy encapsulating HC were used by adding Legumain-targeted RR-11a into the liposomal nanoparticles (178, 179). In another study, the suitability of introducing Curcumin in solid lipid nanoparticles (SLN-curc) or d-α-Tocopheryl polyethylene glycol 1,000 succinate (TPGS) nanoparticles (TPGS-curc) was investigated in Hodgkin's lymphoma in mice, which SLN-curc was more superior compared to TPGS-curc in term of pharmacokinetic profile (180).…”

Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer

“…Substantial evidence revealed that curcumin (4 mg/kg every 2 days for a total of 7 injections) exhibits a better treatment efficacy of doxorubicin (0.4 mg/kg) in cancer due to its efflux inhibitory effect of curcumin [92,93,94]. A study conducted by Guorgui et al [95] has shown that combination of curcumin (5 µM) and doxorubicin (0.4 mg/mL) demonstrated a stronger additive effect by reducing the proliferation of Hodgkin lymphoma (L-540) cells by 79%. The pharmacokinetic study also revealed that curcumin (5 mg/kg) could enhance the absorption of doxorubicin (5 mg/kg) and decrease drug efflux in vivo, suggesting that curcumin downregulates the intracellular levels of ATP-binding cassette (ABC) drug transporters [96].…”

“…The data revealed that TPGS-curc (10 mg/kg body weight) shows a better in vivo kinetic profile than curcumin alone, suggesting that TPGS an ideal formulation to improve curcumin bioavailability in vivo. In addition, formulating curcumin in solid lipid nanoparticles (SLN-curc) (100 mg/kg of curcumin, 5 days per week for 18 days) exhibited a strong anticancer activity compared to curcumin alone (100 mg/kg, 5 days per week for 18 days) [95]. The data showed that SLN-curc increased cell cycle regulator (p21) and diminished the anti-apoptotic (XIAP and Mcl-1) levels [95].…”

“…In addition, formulating curcumin in solid lipid nanoparticles (SLN-curc) (100 mg/kg of curcumin, 5 days per week for 18 days) exhibited a strong anticancer activity compared to curcumin alone (100 mg/kg, 5 days per week for 18 days) [95]. The data showed that SLN-curc increased cell cycle regulator (p21) and diminished the anti-apoptotic (XIAP and Mcl-1) levels [95]. In support of the efficacy of nanoformulation-based curcumin, in vitro study has demonstrated that the efficacy of cell proliferation in dendrosomal curcumin (8.31-13.45 µM) is superior compared to curcumin alone (13 to 30 µM) [120].…”

Passive and active targeting in cancer therapy by liposomes and lipid nanoparticles

“…Conjugation of curcumin with SLN is another report for passive targeting of tumor tissues used in breast cancer with remarkably higher tissue availability [57]. In a similar study, growth inhibition of Hodgkin's lymphoma xenograft was observed by 50.5% in the case of curcumin-SLN receiving group [58]. For passive targeting of glioblastoma and melanoma, temozolomide-SLN showed higher inhibition in proliferation of these types of cancer tissues and lower cytotoxicity in healthy cells compared to temozolomide without SLN [59].…”