Research in Pharmaceutical Sciences
Volume:13 Issue: 4, Aug 2018

During the recent years, more attentions have been focused on lipid base drug delivery system to overcome some limitations of conventional formulations. Among these delivery systems solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are promising delivery systems due to the ease of manufacturing processes, scale up capability, biocompatibility, and also biodegradability of formulation constituents and many other advantages which could be related to specific route of administration or nature of the materials are to be loaded to these delivery systems. The aim of this article is to review the advantages and limitations of these delivery systems based on the route of administration and to emphasis the effectiveness of such formulations.

Human serum albumin (HSA) is the most abundant protein found in human blood and is extensively employed in clinical applications such as hypovolemic shock treatment. Also, there has been a lot of attempt to use HSA as a carrier to deliver various drugs to their specific targets. Thus, clarify of structure, dynamics, functions, and features of HSA-drug complexes play an important role from the viewpoint of pharmaceutical and/or biochemical sciences. In this study, the interaction of letrozole, as a non-steroidal aromatase inhibitor, with HSA has been studied by combining different techniques such as UV-Vis, fluorescence spectroscopy, and computational methods. The binding of letrozole quenches the serum albumin fluorescence intensities. A clear decrease in fluorescence intensities of letrozole-HSA complex with the increase in temperature showed the static mode of fluorescence quenching. The results of Stern-Volmer procedure analysis showed that letrozole is bound only to a site from the HSA. The results of thermodynamic analysis showed that reaction between HSA and letrozole is spontaneous and exothermic. Furthermore, by monitoring the intrinsic fluorescence and using site markers competitive measurement, the binding of letrozole in the neighborhood of Sudlow’s site I of HSA has been proved. Finally, computational methods substantiated the experimental findings and it was revealed that letrozole was bound to Arg-209, Trp-214, Ala-350, and Gly-238 residues of subdomain IIA and IIIA of HSA, respectively.

Opiate tolerance and dependence is a worldwide public health problem and gives a significant burden to society. The aim of this study was to evaluate the effects of metformin (MET) on development and expression of morphine tolerance and dependence in rats. For induction of tolerance, morphine sulfate was injected (10 mg/kg, twice a day, s.c.) for 7 days. Animals received metformin (5 and 50 mg/kg, orally, daily) during the examination period for assessing the development of morphine tolerance and dependence. In order to evaluate the expression of morphine tolerance and dependence, single doses of MET (5 and 50 mg/kg, orally) were administered on day 7. Tail flick test was performed to assess the induction of morphine tolerance. For evaluation of morphine dependence, naloxone-induced jumping (5 mg/kg, s.c.) was monitored. Our results showed that 7 days coadministration of 50 mg/kg of MET significantly reduced the development of morphine analgesic tolerance versus morphine saline treated rats (P

Natural plants have traditionally been used throughout the world for their anti-diabetic effects. The aim of the present study was to investigate the protective effect of hydroalcoholic extract of Trifolium pratens L. (T. pratense) on streptozotocin (STZ) cytotoxicity and insulin concentration from RIN-5F pancreatic β cell line. In this study, possible cytoprotective action of T. pratense extract (using pre-treatment, simultaneous, and post-treatment schedules) against STZ (30 mM) was evaluated using MTT assay. Apoptosis was quantified by fluorescent dye staining. Also, the effect of extract on insulin secretion in low and high glucose media was examined. Data were analyzed by one-way ANOVA test and P

Insulin-like growth factor binding protein-3 (IGFBP-3) is a vital protein exist in circulation which interacts with high affinity to insulin-like growth factor (IGFs) altering their activities. Therefore, the interaction between IGFs and IGFBP-3 has a key role altering large spectrum of activities such as cell cycle progression, proliferation and apoptosis. Despite decades of research, the crystal structure of IGFBP-3 has not been identified possibly due to some technical challenge in its crystallizing. The three-dimensional (3D) structure of IGFBP-3 was predicted using homology modeling, Phyre2, and molecular dynamic. Its interaction with IGF-1 was also identified by HADDOCK software. IGFBP-3 has the most identity with other IGFBPs in N and C-domain; however, its linker domain has lower identity. Our data predicted that IGF-1 structurally interacts with N- domain and linker domain of IGFBP-3. Some conserved residues of IGFBP-3 such as Glu33, Arg36, Gly39, Arg60, Arg66, Asn109, and Ile146 interacts with Glu3, Asp12, Phe16, Gly19, Asp20, Arg21, and Glu58 of IGF-1. In addition, our data predict that the linker domain has a loop structure which covers post translational modification and interacts with IGF-1. The phosphorylation of Ser111 in linker domain, which previously has been shown to induce apoptosis make a repulsive force interrupting this interaction to IGF-1, which enables IGFBP-3 to induce apoptosis. The present study suggests that the linker domain has a key role in recognition of IGFBP-3 with IGF-1.

The role of angiogenesis in tumor progression and metastasis formation has been well recognized. Recent studies have reported that Trigonella foenum-graecum L. (fenugreek) seed extracts have potential anticancer properties. The current study was planned to investigate the anti-angiogenic activity of hydroalcoholic extract of fenugreek (HAEF) in vitro and in vivo. Effect ofHAEF (50-3000 µg/mL) and thalidomide (200-3000 µmol/L), as a positive control, on the viability of human umbilical vein endothelial cells (HUVECs) and 3T3 fibroblast cells was assessed by thiazolyl blue tetrazolium bromide (MTT) assay. Effect of HAEF on vessel-like tube formation by HUVECs was examined in the matrigel-based assay. Furthermore, the chick chorioallantoic membrane (CAM) was used as in vivo model to study the anti-angiogenic effect of HAEF. HAEF, similar to thalidomide, significantly inhibited the viability of HUVECs and 3T3 cells dose-dependently after 24 h. Moreover, both HAEF and thalidomide significantly reduced tube formation by HUVECs in cell culture condition. In CAM model, HAEF and thalidomide caused a significant decline in the number of neovascular points and in the amount of grades 1 and 2 vessels. These findings revealed that fenugreek has cytotoxic and anti-angiogenic effects in vitro and in vivo. Therefore, this medicinal plant can be subjected to further investigations as antitumor agents.

Blockade of α4 integrin by antibodies could be an appropriate treatment strategy in multiple sclerosis and Crohn’s disease. Considering disadvantages of antibodies, other elements (e.g. aptamers) have been proposed for antibodies replacement. Isolation of aptamers through cell-SELEX (systematic evolution of ligands by exponential enrichment) method requires positive and negative α4 integrin expressing cell lines. For a better isolation, we intended to construct a negative cell line lacking of specific ligand binding site of α4 integrin. Escherichia coli strain top 10 was used for truncated integrin subunit α4 (TITGA-4) expression. Human embryonic kidney (HEK)-293T cell was transfected with linearized TITGA-4 plasmid and subsequently screened for stable TITGA-4 expressing cells. Chromosomal DNA of TITGA-4-transfected cells was extracted and the presence of TITGA-4 gene in HEK-293T genome was confirmed by polymerase chain reaction (PCR). The expression level of TITGA-4 on HEK-293T cells was also analysed by real-time PCR and flow cytometry. Real-time PCR and flow cytometric analysis showed significant difference of TITGA-4 expression between untransfected HEK-293T cells compared to transfected cells. The results suggest that we have successfully constructed the truncated integrin α4 expressing HEK-293T cell, which will facilitate further research into the production of antibody, nanobody, and aptamer against α4 integrin.

Quinazoline is one of the most widespread scaffolds amongst natural and synthetic bioactive compounds. Recently the quinazoline derivatives and in particular the 4-anilinoquinazolines have attracted much attention for their anticancer properties due to their capability to stabilize the kinase activity of epidermal growth factor receptor (EGFR). A series of fifteen previously designed and synthesized 4-anilinoquinazoline analogs (4-18) were evaluated for cytotoxic activity on two breast cancer cell lines (MCF-7 and MDA-MB-468). Ligand efficiency and binding mode studies were also done and evaluated for their potentially EGFR inhibitory effects in comparison with imatinib and erlotinib as reference drugs. Among the tested 4-anilinoquinazolines, compound 11, which contains diethoxy at phenyl ring and morpholino pendants at positions 5 and 7 of the quinazoline ring, demonstrated the most potent biological activity on both cell lines. Our new quinazoline derivatives with different substituents such as cyclic or linear ethers and flour groups may be a promising cytotoxic lead compounds for further anti-breast cancer research.

Oxidative stress (OS) is a main mechanism in organophosphorus poisoning. The effects of calcium channel blockers have been confirmed in decreasing of oxidative stress. In the current study, the effects of amlodipine (AM), as a calcium channel blocker, were evaluated on oxidative damages induced by diazinon (DZN) in hippocampus tissue of Wistar rats. Forty-two rats were divided into six groups and treated intraperitoneally for two weeks. Group 1 served as control received vehicle, group 2 was treated with 9 mg/kg of AM, group 3 (positive control) received DZN (32 mg/kg), Groups 4, 5, and 6 were treated with 3, 6, and 9 mg/kg of AM adjunct with DZN (32 mg/kg), respectively. After 14 days, all the animals were sacrificed under anesthesia and hippocampus tissue and blood samples were collected for biochemical analysis and histopathology experiments. The results showed that DZN caused significant increase in lipid peroxidation (P

Polymorphism in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence warfarin dose requirement since patients with CYP2C9*2, CYP2C9*3 and VKORC1 mutant alleles require lower warfarin maintenance doses. Studies have reported the ethnic variations in the frequency of these genes within the various populations in Iran and other parts of the world. However, no such study has been done yet on Kurdish population in Kermanshah. From Kurdish population of Kermanshah province in Iran, a total of 110 patients who had heart surgery and taking warfarin, were genotyped for polymorphisms of VKORC1-1639 G>A, CYP2C9*2, and CYP2C9*3. Polymorphism genotyping was performed by sequencing as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes of MspI, AVAII and KpnI, respectively. The frequencies of VKORC1-1639 GG, GA, and AA genotypes were 42%, 36%, and 22%, respectively and for CYP2C9 1*/1*, 1*/2*, 2*/2*, 1*/3*, 3*/3*, 2*/3* were 71%, 17%, 5.4%, 1.8%, 4.5%, and 0%, respectively. The frequency of VKORC1-1639A allele was 42.3% and the frequencies of CYP2C9*2 and *3 alleles were 14% and 5.4%, respectively. It was indicated that low warfarin dose requirements are strongly associated with the presence of CYP2C9 and VKORC1-1639 variant alleles. Our results confirmed the supply to understand the distribution of genomic biomarkers related to the drugs metabolism for future planning health programs.