Nanostructured Lipid Carrier Co-Loaded with Docetaxel and Magnetic Nanoparticles: Physicochemical Characterization and In Vitro Evaluation
Lung cancer is currently the most prevalent cause of cancer mortality due to late diagnosis and lack of curative therapies. Docetaxel (Dtx) is clinically proven as effective, but poor aqueous solubility and non-selective cytotoxicity limit its therapeutic efficacy. In this work, a nanostructured lipid carrier (NLC) loaded with iron oxide nanoparticles (IONP) and Dtx (Dtx-MNLC) was developed as a potential theranostic agent for lung cancer treatment. The amount of IONP and Dtx loaded into the Dtx-MNLC was quantified using Inductively Coupled Plasma Optical Emission Spectroscopy and high-performance liquid chromatography. Dtx-MNLC was then subjected to an assessment of physicochemical characteristics, in vitro drug release, and cytotoxicity. Dtx loading percentage was determined at 3.98% w/w, and 0.36 mg/mL IONP was loaded into the Dtx-MNLC. The formulation showed a biphasic drug release in a simulated cancer cell microenvironment, where 40% of Dtx was released for the first 6 h, and 80% cumulative release was achieved after 48 h. Dtx-MNLC exhibited higher cytotoxicity to A549 cells than MRC5 in a dose-dependent manner. Furthermore, the toxicity of Dtx-MNLC to MRC5 was lower than the commercial formulation. In conclusion, Dtx-MNLC shows the efficacy to inhibit lung cancer cell growth, yet it reduced toxicity on healthy lung cells and is potentially capable as a theranostic agent for lung cancer treatment.
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Materials
Iron(III) oxide(FeO(OH); hydrated, catalyst grade, 30–50 mesh; cat. #371254 oleic acid (technical grade, 90%), 1-octadecene (ODE; technical grade, 90%), and fish oil were purchased from Sigma-Aldrich (Steinheim, Germany). Docetaxel (Dtx; >98% purity) and trifluoroacetic acid (99% extra purity) were provided by Acros Organics (Fair Lawn, NJ, USA). Sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy 6-nitro) benzene sulfonic acid hydrate (XTT sodium salt) was purchased from GoldBio (St. Louis, MO, USA). Acetone and acetonitrile (HPLC grade) were purchased from Fisher Scientific (Loughborough, UK), while methanol (99.9% purity) was purchased from Merck (Darmstadt, Germany). Lipids including Precirol ATO 5 and Caprylic/Capric triglyceride (MCT; Labrafac CC) were provided by Gattefossé (Saint-Priest, France). Surfactants including lecithin Lipoid S75 and Vitamin E TPGS were provided by Lipoid GmbH (Ludwigshafen, Germany) and Sigma-Aldrich (Steinheim, Germany), respectively. Simulated lung fluid was purchased from R&M Chemicals (Selangor, Malaysia). The materials were all analytical grade and used without additional purification unless otherwise stated.
Idris, A.H.; Che Abdullah, C.A.; Yusof, N.A.; Asmawi, A.A.; Abdul Rahman, M.B. Nanostructured Lipid Carrier Co-Loaded with Docetaxel and Magnetic Nanoparticles: Physicochemical Characterization and In Vitro Evaluation. Pharmaceutics 2023, 15, 1319. https://doi.org/10.3390/pharmaceutics15051319
Read more on Vitamin E TPGS by PMC Isochem here:
