Nanoencapsulation of Hirudo medicinalis proteins in liposomes as a nanocarrier for inhibiting angiogenesis through targeting VEGFA in the Breast cancer cell line (MCF-7).

Introduction: Breast cancer is the most serious cause of women's death throughout the world. Using nanocarrier vehicles to the exact site of cancer upgrades the therapeutic efficiency of the drugs. Capsulation of active proteins in the vesicular liposomes' hydrophilic core is essential to develop a therapeutic protein carrier system. We aimed to encapsulate the medicinal leech saliva extract (LSE) and assess the inhibition of angiogenesis of breast cancer cells by targeting vascular endothelial growth factor A (VEGFA). Methods: In this research, enhanced formulation of liposomal protein was determined by zeta potential analysis, droplet size, drug release assay, and transmission electron microscopy (TEM). Furthermore, a cytotoxicity assay of liposomal LSE was performed to determine the cytotoxic activity of components. For assessing the expression of VEGFA, P53, and hypoxia-inducible factor subunit alpha (HIF1a) genes, Real-Time PCR was applied. Results: Nano liposome was chosen as an enhanced formulation due to its much smaller size (46.23 nm). Liposomal LSE had more practical actions on the MCF-7 cells. As noticed by DAPI staining, apoptosis was extensively greater in treated MCF-7 cells. Wound healing assay demonstrated that MCF-7 cells could not sustain growth at the presence of liposomal LSE and expression of the VEGFA gene was declined in treated cells. Downregulation of VEGFA was evaluated with western blotting technique. Conclusion: It can be concluded that our investigation of the tests confirmed the fact that nano liposomal LSE is a novel promising formulation for anticancer drugs and can significantly improve the penetration of protein drugs to cancer cells.

Development of an albumin decorated lipid-polymer hybrid nanoparticle for simultaneous delivery of methotrexate and conferone to cancer cells.

Aiming to simultaneous target of methotrexate (MTX), as folate antagonist, and conferone (CON) in various cancer cells, the newly lipid/polymer hybrid nanoparticle containing an albumin targeted succinylchitosan shell and lipoid bilayer core composed of hydrogenated soy phosphatidylcholine and cholesterol was synthesized. The covalently conjugating albumin to the external surface of chitosan was accomplished using N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride and N- hydroxyl succinimide as an activating carboxylic group, and nanoliposomes were fabricated via thin film hydration-sonication method. The molecular structure of MTX@CON-targeted lipid/polymer hybrid nanoparticle (MTX@CON-TLPN) were characterized using FTIR spectroscopy, 1H NMR, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The newly nanoparticle with high encapsulation efficiency (85.12%, and 78.4%), acceptable loading capacity (9.8% and 4.6% for MTX and CON) and the stimuli responsiveness drug release behavior in simulated physiologic tumor tissue condition (pH 5.4, 40 °C) was successfully synthetized in the spherical shape with mean average size of approximately 290 nm and ζ-potential of +21 mv. The enhanced efficiency of the targeted nanoparticle was further confirmed using MTT endpoints, cell cycle modulation, apoptosis assessment, and cellular internalization assessments. Collectively, these findings establish the utility of our newly prepared nanoparticle for simultaneous delivery of multiple anti-cancer drugs.

Development and characterization of biocomposite films made from kefiran, carboxymethyl cellulose and Satureja Khuzestanica essential oil.

Kefiran-carboxymethyl cellulose biocomposite films incorporated with Satureja Khuzestanica essential oil were developed and characterized. Results indicated that increase in the concentration of the essential oil increased ultimate tensile strength and contact angle but decreased elongation at break, moisture content and water vapor permeability. It also significantly altered color parameters and the percentage of light transmission in the visible and ultraviolet range. Fourier transform infrared spectroscopy revealed the formation of hydrogen bonds between polymer matrix and essential oil. Scanning electron microscopy showed that the surface structure of the films was homogeneous without porosity. Increase in storage modulus and glass transmission temperature in films incorporated with the essential oil was observed through dynamic mechanical thermal analysis. Moreover, significant increase in antioxidant properties and phenolic compounds were noticed. Ultimately, results obtained from evaluation of antimicrobial characteristics of films indicated their inhibitory effects against Staphylococcus aureus and Escherichia coli bacteria.

Therapeutic Efficacy of Orally Delivered Doxorubicin Nanoparticles in Rat Tongue Cancer Induced by 4-Nitroquinoline 1-Oxide.

PURPOSE: Oral cancer is one of the most significant cancers in the world, and squamous cell carcinoma makes up about 94% of oral malignancies. The aim of the present study was to compare the efficacy of doxorubicin plus methotrexate - loaded nanoparticles on tongue squamous cell carcinoma induced by 4NQO and compare it with the commercial doxorubicin and methotrexate delivered orally on seventy SD male rats. METHODS: 70 rats were divided into five groups. During the study, the animals were weighed by a digital scale once a week. Number of mortalities was recorded in the data collection forms. At the end of the treatment, biopsy samples were taken from rat tongues in order to evaluate the severity of dysplasia and the extent of cell proliferation. The results were analyzed using ANOVA, descriptive statistics and chi-square test. RESULTS: No statistically significant difference was found in the mean weight of five groups (p>0.05). No significant relationship was found between groups and mortality rate (P = 0. 39). In addition, there was a significant relationship between groups and the degree of dysplasia (P <0.001). The statistical analysis showed a significant relationship between groups and the rate of cell proliferation (p <0.001). CONCLUSION: The results of the present study showed that the use of doxorubicin plus methotrexate - loaded nanoparticles orally had more therapeutic effects than commercial doxorubicin plus methotrexate.

The effect of penetration enhancers on drug delivery through skin: a QSAR study.

Skin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin-permeable. A full understanding of the mode of action could be beneficial for the design of potent enhancers and for the choice of the enhancer to be used in the topical formulation of a special drug. In this study, the structural requirements of penetration enhancers have been investigated using the Quantitative Structure-Activity Relationship (QSAR) technique. Activities of naturally occurring terpenes, pyrrolidinone and N-acetylprolinate derivatives on the skin penetration of 5-fluorouracil, diclofenac sodium (DFS), hydrocortisone (HC), estradiol and benazepril have been considered. The resulting QSARs indicated that for 5-fluorouracil and diclofenac sodium, less hydrophobic enhancers were the most active. More precisely, molecular descriptors in the corresponding QSARs indicated the possible involvement of intermolecular electron donor-acceptor interactions. This was in contrast to the skin permeation promotion of hydrocortisone, estradiol and benazepril by enhancers, where a linear relationship between enhancement activity and n-octanol/water partition coefficients of enhancers was evident. The possible mechanisms of penetration enhancement as suggested by the QSARs will be discussed.