Biophysical Evaluation of Water-Soluble Curcumin Encapsulated in ß-Cyclodextrins on Colorectal Cancer Cells.

Curcumin (CUR), a curcuminoid originating from turmeric root, possesses diverse pharmacological applications, including potent anticancer properties. However, the use of this efficacious agent in cancer therapy has been limited due to low water solubility and poor bioavailability. To overcome these problems, a drug delivery system was established as an excipient allowing improved dispersion in aqueous media coupled with enhanced in vitro anticancer effects. Different analyses such as UV-vis spectroscopy, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), solubility and dissolution assays were determined to monitor the successful encapsulation of CUR within the inner cavity of a ß-cyclodextrin (ß-CD) complex. The results indicated that water solubility was improved by 205.75-fold compared to pure CUR. Based on cytotoxicity data obtained from MTT assays, the inclusion complex exhibited a greater decrease in cancer cell viability compared to pure CUR. Moreover, cancer cell migration rates were decreased by 75.5% and 38.92%, invasion rates were decreased by 37.7% and 35.7%, while apoptosis rates were increased by 26.3% and 14.2%, and both caused caspase 3 activation toward colorectal cancer cells (SW480 and HCT116 cells). This efficacious formulation that enables improved aqueous dispersion is potentially useful and can be extended for various chemotherapeutic applications. Preliminary toxicity evaluation also indicated that its composition can be safely used in humans for cancer therapy.

Preparation and Characterization of Chitosan and Inclusive Compound-Layered Gold Nanocarrier to Improve the Antiproliferation Effect of Tamoxifen Citrate in Colorectal Adenocarcinoma (Caco-2) and Breast Cancer (MCF-7) Cells.

Objectives: Cancer diseases have been linked to a huge number of causes that led to deaths in this century along with cardiovascular and lung diseases. Most death-leading types of cancer are colon, lung, breast, and prostate cancers. Due to the remarkable properties of gold (Au) nanocarrier, they are used to deliver and improve tamoxifen (Tam) citrate activity in Caco-2 and MCF-7 cells. Materials and Methods: In this study, preparation of Au nanoparticles (NPs), zeta-potential and size, high resolution transient electron microscopy (HRTEM), high-performance liquid chromatography, ultraviolet-visible spectra, fluorescence microscopy, fourier infrared spectroscopy, and real-time cellular analysis xCELLigence technology were investigated. Results: The zeta-average size of the Tam- ß-cyclodextrin (ß-CD)-hyaluronic acid (HA)-chitosan (Chi)-Au nanocomposite is 82.02 nm with a negative zeta potential of -23.6. Furthermore, HRTEM images showed that, successful formulation of polymer shell around Au core and the Au NP shape is mostly spherical, triangle and irregular. Furthermore, the fluorescence microscope image showed proper cellular uptake of the Tam-ß-CD-HA-Chi-Au nanocomposite in MCF-7 and Caco-2 cells. Additionally, Tam-ß-CD-HA-Chi-Au nanocomposite significantly improved the cytotoxic activity of Tam citrate on Caco-2 cells. IC50 value of Tam reduced from 8.55 µM to 5.32 µM, after 48 h of incubation time (p value <0.00001). Conclusion: This study showed that Tam-ß-CD-HA-Chi-Au nanocomposite is a potential nanocarrier for delivering the drug to Caco-2 and MCF-7 cancer cells, since it has improved Tam citrate activity on colorectal cancer cells. After all, the developed formula showed more effect on Caco-2 than MCF-7. The prepared nanocomposite could be used to improve the cancer therapy in clinical trials.

Combination of Talazoparib and Calcitriol Enhanced Anticancer Effect in Triple-Negative Breast Cancer Cell Lines.

Monotherapy for triple-negative breast cancer (TNBC) is often ineffective. This study aimed to investigate the effect of calcitriol and talazoparib combination on cell proliferation, migration, apoptosis and cell cycle in TNBC cell lines. Monotherapies and their combination were studied for (i.) antiproliferative effect (using real-time cell analyzer assay), (ii.) cell migration (CIM-Plate assay), and (iii.) apoptosis and cell cycle analysis (flow cytometry) in MDA-MB-468 and BT-20 cell lines. The optimal antiproliferative concentration of talazoparib and calcitriol in BT-20 was 91.6 and 10 µM, respectively, and in MDA-MB-468, it was 1 mM and 10 µM. Combined treatment significantly increased inhibition of cell migration in both cell lines. The combined treatment in BT-20 significantly increased late apoptosis (89.05 vs. control 0.63%) and S and G2/M populations (31.95 and 24.29% vs. control (18.62 and 12.09%)). Combined treatment in MDA-MB-468 significantly increased the S population (45.72%) and decreased G0/G1 (45.86%) vs. the control (26.79 and 59.78%, respectively). In MDA-MB-468, combined treatment significantly increased necrosis, early and late apoptosis (7.13, 33.53 and 47.1% vs. control (1.5, 3.1 and 2.83%, respectively)). Talazoparib and calcitriol combination significantly affected cell proliferation and migration, induction of apoptosis and necrosis in TNBC cell lines. This combination could be useful as a formulation to treat TNBC.

Fabrication and Evaluation of Transdermal Microneedles for a Recombinant Human Keratinocyte Growth Factor.

OBJECTIVES: Microneedle transdermal patches are a combination of hypodermic needles and transdermal patches used to overcome the individual limitations of both injections and patches. The objective of this study was to design a minimally invasive, biodegradable polymeric recombinant human keratinocyte growth factor (rHuKGF) microneedle array and evaluate the prepared biodegradable microneedles using in vitro techniques. MATERIALS AND METHODS: Biodegradable polymeric microneedle arrays were fabricated out of poly lactic-co-glycolic acid (PLGA) using the micromolding technique under aseptic conditions, and the morphology of the microneedles was characterized using light microscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to rule out drug-polymer interactions. Standard procedures were used to analyze the prepared microneedle arrays for in vitro drug release and to perform a microneedle insertion test. Enzyme-linked immunosorbent assay was used to quantify rHuKGF. RESULTS: The PLGA polymer was safe for use in the fabrication of rHuKGF microneedles as there was no interaction between the drug and the polymer. The fabricated rHuKGF microneedle arrays had fully formed microneedles with a height of 600 µm and a base of 300 µm. The drug from the microneedle patch was released in vitro within 30 minutes. The strength of the microneedles in the patch was good, as they were able to reach a depth of 381±3.56 µm into parafilm without any structural change or fracture. CONCLUSION: Microneedle transdermal patches were successfully prepared for rHuKGF, and their evaluation suggested excellent quality and uniformity of patch characteristics. This can have potential applications in the therapeutic arena, offering advantages in terms of reduced dosing frequency, improved patient compliance, and bioavailability.

Formulation and evaluation of voriconazole ophthalmic solid lipid nanoparticles in situ gel.

In the present investigation, solid lipid nanoparticles (SLNs)-loaded in situ gel with voriconazole drug was formulated. Further, the formulation was characterized for pH, gelling capacity, entrapment efficiency, in vitro drug release, drug content, and viscosity. Voriconazole is an antifungal drug used to treat various infections caused by yeast or other types of fungi. Film hydration technique was used to prepared SLNs from lecithin and cholesterol. Based on the entrapment efficiency 67.2-97.3% and drug release, the optimized formulation NF1 of SLNs was incorporated into in situ gels. The in situ gels were prepared using viscosity-enhancing polymers such as Carbopol and (hydroxypropyl)methyl cellulose (HPMC). Formulated SLN in situ gel formulations were characterized, which showed pH 4.9-7.1, drug content 65.69-96.3%, and viscosity (100 rpm) 120-620 cps. From the characterizations given above, F6 was optimized and evaluated for microbial assay and ocular irritation studies. Microbial assay was conducted by the cup-plate method using Candida albicans as the test organism. An ocular irritation study was conducted on albino rabbits. The results revealed that there was no ocular damage to the cornea, conjunctiva, or iris. Stability studies were carried out on the F6 formulation for 3 months, which showed that the formulation had good stability. These results indicate that the studied SLNs-loaded in situ gel is a promising vehicle for ocular delivery.