glyceryl-behenate and Breast-Neoplasms

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator used for treatment and protection against postmenopausal osteoporosis. The drug has been used for protection against breast cancer and more recently, for management of the disease by virtue of its estrogen antagonist action. However, the drug has reduced bioavailability related to low water solubility and first pass metabolism. To surmount these pitfalls, this study aimed at developing and optimizing RLX-loaded semisolid self-nanoemulsifying system (SSNES) with minimized globule size to improve the drug solubility, tumor penetration, and consequently antitumor activity. A simplex lattice mixture design was employed for the formulation and optimization of SSNESs. The mixture components, namely, Compritol® 888 ATO, Tween 20, and polyethylene glycol 200 exhibited significant effect on globule size at P < 0.05. The optimized formulation with globule size of 109.19 ± 2.11 nm showed acceptable thermodynamic stability under stress conditions. Anti-cancer efficacy of the obtained formulation was evaluated in MCF-7 breast cancer cell line. MTT viability assay revealed that RLX-loaded SSNES notably inhibited MCF-7 cell proliferation. Flow cytometry and dual staining with annexin V-FITC/PI were used to assay this anti-proliferative effect and induction of apoptosis, respectively. Cells treated with RLX-loaded SSNES showed significant arrest at G2/M phase associated with significant increase in early/late-stages of apoptotic and necrotic cells. The results exhibited that RLX-loaded SSNES induces apoptosis via the activation of caspase-3 and loss of mitochondrial membrane potential. Accordingly, the proposed SSNES could be regarded as a promising platform for enhancing RLX antitumor activity against breast cancer.

Topics: Animals; Apoptosis; Breast Neoplasms; Fatty Acids; Female; Humans; MCF-7 Cells; Raloxifene Hydrochloride; Rats; Rats, Wistar

Metastasis causes the most breast cancer-related deaths in women. Here, we investigated the antitumor effect of solid lipid nanoparticles (SLN-DTX) when used in the treatment of metastatic breast tumors using 4T1-bearing BALB/c mice.. Solid lipid nanoparticles (SLNs) were produced using the high-energy method. Compritol 888 ATO was selected as the lipid matrix, and Pluronic F127 and Span 80 as the surfactants to stabilize nanoparticle dispersion. The particles had high stability for at least 120 days. The SLNs' dispersion size was 128 nm, their polydispersity index (PDI) was 0.2, and they showed a negative zeta potential. SLNs had high docetaxel (DTX) entrapment efficiency (86%), 2% of drug loading and showed a controlled drug-release profile. The half-maximal inhibitory concentration (IC. These results indicate that DTX-loaded SLNs may be a promising carrier to treat breast cancer and in metastasis prevention.

Topics: Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Disease Models, Animal; Docetaxel; Drug Carriers; Fatty Acids; Female; Hexoses; Inhibitory Concentration 50; Lipids; Lung Neoplasms; Mice; Mice, Inbred BALB C; Nanoparticles; NIH 3T3 Cells; Particle Size; Poloxamer

Nanotherapeutics in cancer treatment are dominating global science and research, and have been recognized as the pioneering medical care regimen. Raloxifene (RLN) has been used for its anti-proliferative action on mammary tissue, however, it suffers from poor oral bioavailability. This investigation gives an account of the design and development of RLN-loaded nanostructured lipid carriers (RLN-NLCs) using a simple and scalable ultrasonication method for improved oral efficacy and limited offsite toxicity using Compritol

Topics: Administration, Oral; Animals; Antineoplastic Agents; Breast Neoplasms; Drug Carriers; Ethylene Glycols; Fatty Acids; Female; Humans; MCF-7 Cells; Nanostructures; Raloxifene Hydrochloride; Rats, Wistar; Selective Estrogen Receptor Modulators

The harmful dose-dependent side effects of chemotherapy drugs have caused the discovery of novel perspective to evaluate chemotherapy protocols. In this study, the potential application of Compritol was investigated as a major scaffold into nanostructured lipid careers to highlight myricetin efficiency in treatment of breast cancer cells along with codelivery of docetaxel (DXT). Characterization of myricetin-loaded NLCs was carried out by measuring the particle size and zeta potential, using the scanning electron microscopy. MTT, DAPI staining, flow cytometric, and RT-PCR (real-time) assays were used to recognize novel formulation behavior on cell cytotoxicity as well as recognizing molecular mechanism of formulation concerning apoptosis phenomenon. Myricetin-loaded NLCs reduced the cell viability from 50 ± 2.3 to 40 ± 1.3% (p < 0.05). Percentage of apoptosis improved with combination treatment of myricetin-loaded NLCs and DXT in the MDA-MBA231 breast cancer cells. Expression of antiapoptotic genes (survivin, Cyclin B1, and Mcl1) indicated a significant reduction in factor along with increment in proapoptotic factor Bax and Bid mRNA rates. Overall, our results represented that the NLC delivery system could be a promising strategy to enhance the effect of anticancer agents such as DXT on breast cancer.

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Docetaxel; Drug Carriers; Drug Liberation; Fatty Acids; Flavonoids; G1 Phase Cell Cycle Checkpoints; Humans; Nanoparticles

Camptothecin (CPT) and its analogs exhibit remarkable anti-tumor activity, due to their ability to inhibit DNA topoisomerase I. However, its use is limited by the lack of solubility and stability of the active lactone form. An attractive alternative is the encapsulation of CPT within liposomes. In this study, CPT was incorporated into solid lipid nanoparticles (SLN) based on the triglyceride, Compritol 888 ATO, using supercritical fluid technology without requiring the use of harmful solvents. This drug delivery system was characterized and its cytotoxicity effect was evaluated by measuring MCF7 and MCF10A cell viability as a function of drug loading during a 48-h treatment. Results showed that after 10 h of treatment, MCF7 cells displayed an IC50 of 0.23±0.034 μM at a 1:5 (CPT:SLN) loading and 0.22±0.027 μM at a 1:10 loading, whereas MCF10A cells displayed an IC50 of 0.40±0.036 μM at 1:5 and 0.60±0.063 μM at 1:10. On the other hand, the IC50 of free CPT was 0.57±0.035 μM and 1.07±0.077 μM for MCF7 and MCF10A cells, respectively. Cellular uptake and retention measurements in both cells displayed a two-fold increase when using the SLN formulation. The results from this study showed that the cytotoxic effects of CPT in a SLN formulation improved when compared with those seen with free CPT. The results of this study showed that delivery of CPT as a SLN formulation could be a promising strategy for enhancing its chemotherapeutic effects.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Camptothecin; Cell Survival; DNA Topoisomerases, Type I; Drug Carriers; Drug Delivery Systems; Fatty Acids; Female; Humans; Inhibitory Concentration 50; Lipids; Liposomes; MCF-7 Cells; Nanoparticles; Solubility; Topoisomerase I Inhibitors