The Influence of Pluronic F68 and F127 Nanocarrier on Physicochemical Properties, In vitro Release, and Antiproliferative Activity of Thymoquinone Drug

BACKGROUND: This study reports on hydrophobic drug thymoquinone (TQ), an active compound found in the volatile oil of Nigella sativa that exhibits anticancer activities. Nanoformulation of this drug could potentially increase its bioavailability to specific target cells.

OBJECTIVE: The aim of this study was to formulate TQ into polymer micelle, Pluronic F127 (5.0 wt %) and Pluronic F68 (0.1 wt %), as a drug carrier to enhance its solubility and instability in aqueous media.

MATERIALS AND METHODS: Polymeric micelles encapsulated TQ were prepared by the microwave-assisted solvent evaporation technique. Fourier transform infrared spectroscopy and ultraviolet-visible spectrophotometer were utilized for qualitative confirmation of micelles encapsulation. The surface morphology and mean particle size of the prepared micelles were determined by using transmission electron microscopy (TEM). Cytotoxicity effect was studied using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.

RESULTS: Dynamic laser light scattering (DLS) technique showed hydrodynamic size distribution of optimized micelles of 50 nm, which was in close agreement with the mean particle size obtained from TEM of about 51 nm. Drug release study showed the maximum percentage of TQ release at 61% after 72 h, while the entrapment efficiency of TQ obtained was 46% using PF127. The cytotoxic effect of PF127-encapsulated TQ was considerably higher compared to PF68-encapsulated TQ against MCF7 cells, as they exhibited IC50value of 8 μM and 18 μM, respectively.

CONCLUSION: This study suggests higher molecular weight Pluronic polymer micelles (F127) with hydrophilic-hydrophobic segments which could be used as a suitable candidate for sustainable delivery of TQ. However, comprehensive studies should be carried out to establish the suitability of Pluronic F127 as a carrier for other drugs with similar challenges as TQ.

SUMMARY: There is a rising interest in integrating nanotechnology with medicine, creating a nanomedicine aiming for high efficiency and efficacy of disease diagnosis and treatment. In drug delivery, the term nanomedicine describes the nanometer-sized range (1-1000 nm) of a multi-component drug for disease treatments. As such, liposome-based nanoparticulate delivery vehicles have been approved by the Food and Drug Administration (FDA) for clinical applications. The main purpose of introducing nanoscale drug delivery is to improve the pharmacological and pharmacokinetic profiles of therapeutic molecules. Drug or therapeutic molecules can be either released through the cleavage of a covalent linkage between drug molecules and polymers (conjugation) or through the diffusion from a drug and polymer blended matrix (physical encapsulation). Polymers play an important role in the design of nanocarriers for therapeutic deliveries. In Asia, Nigella sativa seed oil has been used traditionally for its various medicinal benefits. One of its most potent compound which is thymoquinone has been intensively investigated for its anti-cancer effects in colorectal carcinoma, breast adenocarcinoma, osteosarcoma, ovarian carcinoma, myeloblastic leukemia, and pancreatic carcinoma. In addition, it is reported to show anti-inflammatory potential, antidiabetic, antihistaminic effects, as well as the ability to alleviate respiratory diseases, rheumatoid arthritis, multiple sclerosis, and Parkinson's disease. This study aims to formulate and characterize different pluronic-based thymoquinone nanocarrier and investigate its effect against breast cancer cells Abbreviations Used: ATR-IR: Attenuated Total Reflectance-Infrared Spectroscopy, CH3CN: Acetonitrile, DLS: Dynamic Light Scattering, MTS: [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, NPs: Nanoparticles, PF127/TQ: Pluronic F127 encapsulated TQ, PF68/TQ: Pluronic F68 encapsulated TQ, PLGA: Poly-(D,L-lactide-co-glycolide), PVA: Poly-vinylalcohol, TQ: Thymoquinone, UV/VIS: Ultravioletvisible spectrophotometry.