Thymoquinone poly (lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential.
Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy confirmed particle diameter between 150 and 200nm. Electrophoretic gel shift mobility assay showed that TQ nanoparticles (NP) were more active than TQ in inhibiting NF-kappaB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), those are markers of cell proliferation, metastasis and angiogenesis, respectively. TQ-NP were also more potent than TQ in suppressing proliferation of colon cancer, breast cancer, prostate cancer, and multiple myeloma cells. Esterase staining for plasma membrane integrity revealed that TQ-NP were more potent than TQ in sensitizing leukemic cells to TNF- and paclitaxel-induced apoptosis. Overall our results demonstrate that encapsulation of TQ into nanoparticles enhances its anti-proliferative, anti-inflammatory, and chemosensitizing effects.
Ravindran
Jayaraj
J
Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, United States.
Nair
Hareesh B
HB
Sung
Bokyung
B
Prasad
Sahdeo
S
Tekmal
Rajeshwar R
RR
Aggarwal
Bharat B
BB
D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000893:Anti-Inflammatory Agents; D016227:Benzoquinones; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C003466:thymoquinone