Current Pharmaceutical Biotechnology - Volume 19, Issue 4, 2018

Background: Targeting chemotherapeutic agents to the tumor tissues and achieving accumulation with ideal release behavior for desired therapy requires an ideal treatment strategy to inhibit division of rapid growing cancerous cells and as an outcome improve patient's quality of life. However, majority of the available anticancer therapies are well known for their systemic toxicities and multidrug resistance. Methods: Application of nanotechnology in medicine have perceived a great evolution during past few decades. Nanoemulsion, submicron sized thermodynamically stable distribution of two immiscible liquids, has gained extensive importance as a nanocarrier to improve chemotherapies seeking to overcome the limitations of drug solubilization, improving systemic delivery of the chemotherapeutics to the site of action to achieve a promising inhibitory in tumor growth profile with reduced systemic toxicity. Results and Conclusion: This review has focused on potential application of nanoemulsion in the translational research and its role in chemotherapy using oral, parenteral and transdermal route to enhance systemic availability of poorly soluble drug. In summary, nanoemulsion is a multifunctional nanocarrier capable of enhancing drug delivery potential of cytotoxic agents, thereby, can improve the outcomes of cancer treatment by increasing the life-span of the patient and quality of life, however, further clinical research and characterization of interactive reactions should need to be explored.

Background: The observation that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists such as ketamine transiently induce schizophrenia-like positive, negative and cognitive symptoms has led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. NMDAR hypofunction can explain many schizophrenia symptoms directly due to excitatory-to-inhibitory (E/I) imbalance, but also dopaminergic dysfunction itself. However, so far no new drug targeting the NMDAR has been successfully approved. In the search for possible biomarkers it is interesting that ketamine-induced psychopathological changes in healthy participants were accompanied by altered electro-(EEG), magnetoencephalographic (MEG) and functional magnetic resonance imaging (fMRI) signals. Methods: We systematically searched PubMed/Medline and Web of Knowledge databases (January 2006 to July 2017) to identify EEG/MEG and fMRI studies of the ketamine model of schizophrenia with human subjects. The search strategy identified 209 citations of which 46 articles met specified eligibility criteria. Results: In EEG/MEG studies, ketamine induced changes of event-related potentials, such as the P300 potential and the mismatch negativity, similar to alterations observed in schizophrenia patients. In fMRI studies, alterations of activation were observed in different brain regions, most prominently within the anterior cingulate cortex and limbic structures as well as task-relevant brain regions. These alterations were accompanied by changes in functional connectivity, indicating a balance shift of the underlying brain networks. Pharmacological treatments did alter ketamine-induced changes in EEG/MEG and fMRI studies to different extents. Conclusion: This review highlights the potential applicability of the ketamine model for schizophrenia drug development by offering the possibility to assess the effect of pharmacological agents on schizophrenia- like symptoms and to find relevant neurophysiological and neuroimaging biomarkers.

Background: Research involving snake venom has gradually surpassed the simple discovery of new molecules using purification and structural characterization processes, and extended to the identification of their molecular targets and the evaluation of their therapeutic potential. Nevertheless, this only became possible due to constant progress in experimental biology and protein purification approaches. Objective: This review aims to discuss the main components of snake venoms that have been investigated for biotechnological purposes, and to discover how these promising biomolecules were obtained with the satisfactory degree of purity that have enabled such studies. Advances in purification technologies of various snake venom molecules have allowed for important discoveries of proteins and peptides with different biomedical and biotechnological applications. Result and Conclusion: It is believed that significant experimental and computational advances will arise in similar proportions in the coming years that will allow researchers to map the molecular regions responsible for their pharmacological actions, their respective mechanisms of action and their cell targets.

Background: Despite the significance of the traditional risk factors, recently published studies have suggested that inflammatory processes and variations in the genetics of the inflammatory system may participate in the initiation of atherosclerosis and its complications. Objective: To investigate the possible association between CD14 C(-260)T (rs2569190) gene polymorphism and the risk of acute myocardial infarction in the Egyptian population. Methods: We enrolled 100 acute myocardial infarction patients in addition to 107 healthy controls. Deoxyribonucleic acid was extracted, purified and used for the genotype assay of C(-260)T polymorphism in promoter region of CD14 gene. Genotyping was conducted using polymerase chain reactionrestriction fragment length polymorphism. Polymerase chain reaction product was digested using a restriction enzyme and the digestion products were specified. Serum CD14 levels were determined by Enzyme Linked Immunosorbent Assay. Results: CD14 genotypic distribution (CC: 15.9% vs. 16%, CT: 62.6% vs. 58%, TT: 21.5% vs. 26% in controls versus acute myocardial infarction patients, p > 0.05 for all variables) and allele frequencies (C allele: 47% vs., 45%, T allele: 52% vs. 55% in controls versus acute myocardial infarction patients, p > 0.05 for all variables) did not show a statistical significant difference. Serum CD14 levels were elevated in acute myocardial infarction patients (5.73±0.62 vs. 4.48±0.28 pg/ml, p < 0.05). However, there was no statistically significant difference in serum CD14 levels among different CD14 genotypes. Conclusion: CD14 C-(260)T polymorphism is not associated with incidence of acute myocardial infarction in Egyptians who showed elevated serum CD14 levels in comparison to healthy individuals.

Background: Development of new recombinant biotechnology products has greatly expanded in the field of modern pharmacy and medicine. Since biological recombinant molecules are sensitive, simple or composed proteins, their function is heavily dependent on their structure. In addition to their efficacy, biological medicinal products could show side effects such as immunogenicity. Therefore, detection and characterization of protein structural variants is essential during development and quality control of therapeutic proteins that might trigger immunogenic response in organism. Methods: This article includes proposed detection and characterization of aggregated, as well as other modified forms of monoclonal antibodies (mAb), by using selected chromatographic and spectrometric methods. Additionally, selected mAb's aggregates and modified structural variants of monoclonal antibodies were subjected to the immature monocyte-derived dendritic cells' (DC) examination experiment for monitoring of activated DC cells in order to determine potential immunogenicity of mAb structural variants. Furthermore, potential innate immunogenic response of peripheral blood mononuclear cells (PBMC) cultures to mAb aggregates was also evaluated by measuring pro-inflammatory cytokine response during early exposure of PBMCs to different mAb samples and by determining the effect of mAb aggregates on PBMC proliferation during long-term cultures. Result and Conclusion: All developed and proposed analytical methods and immunological in vitro DC and PBMC assays, could be used as platform for complementary analytical characterization and determination of potential for immunogenicity for all biopharmaceutical products which contain monoclonal antibodies as active pharmaceutical ingredients.