Current Pharmaceutical Design - Volume 24, Issue 29, 2018

Acquired Immune Deficiency Syndrome (AIDS) is the most serious stage of Human Immunodeficiency Virus (HIV) infection. The combinatorial Anti-Retroviral Therapy (cART) is widely used in suppressing HIV-1 infection and enhancing life span of infected patients to a significant level. However, delivery of therapeutic molecules is still a major challenge in vivo. The studies showed that the anti-HIV drugs delivered via nanocarriers could be selectively accumulated in infected cells accompanied by low side effects. On the other hand, HIV-1 infection kinetics is different in macrophages and T-cells suggesting various effects of antiretroviral drugs against HIV-1 in these target cells. Current anti-HIV therapeutic studies have focused on developing drug delivery systems targeted specifically to HIV-infected host cells. Indeed, the drug targeting can significantly lead to reduce in drug toxicity, drug dose, and increase in treatment efficacy through localizing its pharmacological activity to the site of interest. This review describes development of novel drug targeting systems used in suppressing the transmission and treatment of HIV infections.

Background: The small GTPase Rho family and its effectors, Rho-kinases (ROCK) play essential roles in the actin cytoskeleton organization and coordinate a broad range of cellular functions, such as inflammatory responses, cell contractility, migration, adhesion, proliferation, and apoptosis. Methods: The goal of this work is to review existing literature about systemic sclerosis and Behçet's disease in relation to ROCK. Results: There are some evidence that ROCK expression is elevated in patients with systemic sclerosis and Behçet's disease. Rho/ROCK gene polymorphisms have been shown to be associated with these disorders. Endothelial function is also impaired in these autoimmune diseases. Rho/Rho-kinase pathway might have a crucial role in endothelial, vascular, and fibrotic pathologies. Conclusion: Dysregulation in the Rho/ROCK pathway may represent a common pathogenic mechanism in multiple autoimmune disorders. Current evidence indicate that Rho/ROCK genes might be risk factors, and can contribute to susceptibility and development of systemic sclerosis and Behçet's disease. These studies may also provide important insights into the future development or use of potential novel therapeutic approaches, such as selective Rho-kinase inhibitors, for the treatment of patients with systemic sclerosis and Behçet's disease.

Tea polyphenols have received much attention from the pharmaceutical and food industries owing to their extraordinary antioxidant and antibacterial characteristics. However, tea polyphenols are very unstable in processing and storage, since they are sensitive to the environmental factors like temperature, light and pH. Therefore, the effective application of tea polyphenols requires a protective mechanism to maintain its activity. The utilization of compounded tea polyphenols, instead of raw materials, can potentially help to improve their stability. This review focuses on the summarization of the compounding technologies for tea polyphenols, including physical technologies, chemical-interfacial technologies and nano-scale compounding technologies. Of which, the emerging nano cellulose bio-carrier, as a promising technology, is particularly proposed.

Background: The pharmacophore concept in modern drug research is of great importance and promotes the development of drug industry as indicated by the number of publications available. Methods: In this article, we reviewed and highlighted some successful examples of pharmacophore modeling, which was applied either in virtual screening for efficient hit discovery or in the optimization of the lead compounds. Meanwhile, the analysis of some important aspects of pharmacophore modeling such as a database, the software was listed as well. Results: Based on the analysis of these examples, we intended to provide an overview of pharmacophore-based virtual screening, which we hope to help readers gain insight into this powerful technique. Conclusion: Owing to its' convenience and efficiency, pharmacophore presents an essential method for drug discovery.

Background: The β-caryophyllene (BCP), a phytocannabinoid present in various essential oils, demonstrated selective action on the CB2 endocannabinoid receptor and attracted considerable attention because of its several pharmacological activities. Despite this recognized potential, this hydrophobic compound is a volatile and acid-sensitive sesquiterpene that readily oxidizes when exposed to air, and has low bioavailability in oral formulations. Thus, the development of formulations that guarantee its stability and increase its bioavailability is a challenge for its use in the pharmaceutical field. Methods: The present review brings for the first time a comprehensive overview of the controlled and vectorized release formulations tested for BCP administration. Among these, we have addressed nanoemulsions, inclusion complexes with cyclodextrins, liposomes, wound dressings, nanocomposites and nanoparticles. A literature search was performed on Pubmed, Web of Science and Science direct, and patents documents were also searched on European Patent Office, World Intellectual Property Organization and Brazilian National Institute of Industrial Property. Results: The systems presented here may represent an interesting approach to overcome the limitations already mentioned for this terpene. These systems proved to be promising for improving solubility, stability and controlled release of this pharmacological relevant sesquiterpene. In the industrial field, some companies have filed patent applications for the commercial use of the BCP, however, the use of pharmaceutical formulations still appeared moderate. Conclusion: This prospective study evidenced the new perspectives related to BCP vectorization systems in the pharmaceutical and industrial marketing field and may serve as a basis for further research and pharmaceutical use of this powerful cannabinoid.

Carvacrol has a high therapeutic potential, with in vitro studies showing promising results in different cellular models using a variety of methodological designs. Therefore, the objective of this study was to conduct a systematic review to analyze the pharmacological effects of carvacrol in in vitro studies. A comprehensive search of the literature was made using four databases: Science Direct, Scopus, MEDLINE-PubMed, and Web of Science using different combinations of the following keywords: carvacrol, drug therapy, therapeutic uses, in vitro study. The search of the databases was for studies conducted in the period up to and including September 2016. A total of 3,269 studies were initially identified, with only 31 meeting the inclusion criteria. The included studies contained a variety of in vitro models able to determine the properties of Carvacrol. The following properties of Carvacrol were identified: antimicrobial (7 studies), bactericidal (4), bactericidal and antifungal (1), antiinflammatory (4), anticancer (4), mutagenic (4), antioxidant (3), antifungal (3), antidepressant (1), as a modulator of nerve impulses (1) and an immunological modulator (1). The In vitro studies with Carvacrol included in this review showed a diversity of models and confirmed the therapeutic potential of this product in relation to several diseases.

Background: Single Boron Atom Compounds (SBACs) have been used for drug discovery in diseaseassociated proteins due to the empty p-orbital in the atomic structure of boron, which allows it to experience diverse binding modes during molecular recognition with a range of proteins. Objective: During the molecular recognition process with a protein target, SBACs can assume an anionic tetragonal arrangement or a neutral trigonal planar structure to produce four possible reversible covalent or non-covalent binding modes with a protein. However, the development of new SBACs has been hampered by the fact that most of the force fields present in many of the software packages used in drug design lack the various types of boron atom parameters. Methods: We review in silico studies in which a series of theory-based computational strategies have been used to overcome the lack of boron parameters in most of the force fields used in drug design. Results: The modeling studies discussed in this review have provided substantial insight into the molecular recognition of SBACs targeting different receptors, including the elucidation of some of the key interactions, which serve as a guide for the development of selective SBACs. Conclusion: Although the strategies employed in many of the studies presented here should serve in the development of selective SBACs, it is clear that the development of the precise force field parameters, which include not only the individual atom types but also the entire molecule, is still lacking, yet it is a necessary requirement for the design of new SBACS as well as for gaining insight into their molecular recognition.

Purpose: Pars plana vitrectomy (PPV) and silicone oil endotamponade have been used as a treatment in rhegmatogenous retinal detachment (RRD). Improvement in the modality of spectral-domain optical coherence tomography (SD-OCT) allows for the assessment of ganglion cell layer-inner plexiform layer (GCL-IPL) in the macular region. Information about the GCL-IPL status may be a response to the question as to why the visual recovery after PPV with silicone oil tamponade is incomplete. The aim of the study was to evaluate the impact of silicone oil on GCL-IPL and compare it with other endotamponade types such as Sulfur hexafluoride gas (SF6), Perfluoropropane gas (C3F8) used during PPV performed due to RRD. Patients and Methods: The study involved 57 eyes after PPV and 57 healthy, control eyes of patients with primary RRD who had undergone successful PPV. The patients were divided into three subgroups depending on the endotamponade type, and were tracked with complete ophthalmological examination during a period of 6 months. PPV with internal tamponade silicone oil, 24% SF6 or 14% C3F8 was performed. The medical records were reviewed and compared between the groups. Results: SD-OCT analysis detected a significant reduction of average GCL-IPL thickness and reduction of GCLIPL parameter in almost all examined sectors in the group with silicone oil endotamponade during all follow-up visits (P<0.05). The study showed a significant vision deterioration in the silicone oil group in comparison with the SF6 group on all follow-up visits (P<0.05). Conclusion: This is the first in vivo SD-OCT study describing the toxic effect of silicone oil endotamponade on GCL-IPL complex after PPV for RRD. The study confirmed that the GCL-IPL complex value can be a predictive factor for assessing the final visual acuity. SD-OCT should be recommended as a clinical standard in the followup treatment of patients after PPV for RRD, especially with the use of silicone oil endotamponade. Plain Language Summary: The aim of the study was to examine the impact of silicone oil on the ganglion cell complex. The ganglion cell is a neuron type located in the retina and takes part in transmitting visual information from the retina to the brain. Silicone oil is a substance used during eye surgery called pars plana vitrectomy. This tamponade type acts to hold the retina in a proper position. However, during the retinal detachment, which is the separation of the retina from the layer underneath, a reduction of neurons is observed. We decided to use a new technology device called SD-OCT to determine the thickness of the ganglion cell complex. We compared the impact of silicone oil with other tamponade types. We found that silicone oil causes a reduction in the ganglion cell complex. Moreover, we observed vision deterioration in eyes treated with a silicone oil tamponade. The research describes the toxic effect of silicone oil on ganglion cells. Ganglion cell values may be used to determine visual improvement or deterioration after eye surgery with silicone oil tamponade. SD-OCT should be a clinical standard in monitoring patients with silicone oil tamponade.