Current Drug Research Reviews - Volume 13, Issue 1, 2021

Conventional drug discovery is a time consuming and expensive expedition with less clinical preference achievement proportion intended for breast cancer therapy. Even if numerous novel approaches to the conformation of drugs have been introduced for breast cancer therapy, they are yet to be implemented in clinical practice. This tempting strategy facilitates a remarkable chance to take the entire benefit of existing drugs. Despite drug repurposing significantly decrease the investigational period and cost, it has got many objections and issues. Scaffold repurposing is an approach that procures a novel significance on the decrepit motto of “to commencement with a pristine drug” . Hence, we move into a probable and nearer approach, the exploitation of scaffolds, which was originally developed for other purposes, including anti-tumor activity. In this review, we summarize different drugs and scaffolds used in breast cancer therapy.

Background: SeDeM (Sediment Delivery Model) expert system is a preformulation tool employed for evaluating direct compression suitability of various excipients. SeDeM is a 12 parameters derived diagram and SeDeM-ODT (Sediment Delivery Model-Orodispersible tablets) is a 15 parameters derived diagram that can be used as a research tool for reducing the product development time. The best possible excipients for a specified pharmaceutical active ingredient could be screened for direct compression suitability. Objective: SeDeM expert system has been successfully used and implemented for characterizing galenic properties of pharmaceutical excipients, direct compression suitability of excipients, development of ODT formulations, development of sustained-release formulations, and development of tablets of taste-masked drugs. Conclusion: In the present review paper, the development and applications of SeDeM and SeDeMODT systems have been discussed in detail.

Background: Onychomycosis is by far the most common finger or toe nail fungal infectious disease caused by dermatophytes, non-dermatophytic molds or yeast. It accounts for 50% of the total nail disorders, and affects patients physically, socially, and psychologically and can seriously influence their quality of life. Objectives: Oral antifungals are routinely used to treat the nail fungal disease; however oral therapy is associated with severe side effects and longer treatment times. In recent years, drug delivery directly into the nail or nail bed has gained attention and various topical products have been tested that can cure the disease when applied topically or transungually. Nevertheless, drug penetration into and through the nail is not straightforward and requires chemicals to improve its permeability or by applying physical stress to promote drug penetration into and through the nail. This lucid review presents an overview of various causes of onychomycosis, current therapeutic approaches, and efforts aimed at increasing the permeability of nails through various strategies such as chemical, physical and mechanical methods for permeation enhancement. Conclusion: Various strategies have been proposed for the treatment of onychomycosis, however, much research into a more precise and effective therapy is still required.

Background: Poor water soluble compounds are difficult to develop as drug products using conventional formulation techniques. Objective: In the present study, the potential of Eudragit RS-100 nanosuspension as a new vehicle for the improvement of the delivery of drugs to the intraocular level was investigated. Methods: Solvent evaporation technique has been employed for nanosuspension preparation. Surfactant concentration and drug to polymer ratio has been optimized using 3² factorial design to achieve desired particle size, entrapment efficiency and percent permeation responses as dependent variables. All the formulations were characterized for particle size, zeta potential, polydispersity index (PDI), Fourier Transform Infrared Spectroscopy (FTIR), Differential scanning calorimetery (DSC), X-ray Diffraction (XRD) analysis, viscosity, antifungal study and Transmission Electron Microscopy (TEM). Secondly, itraconazole eye drop was prepared by using sulfobuty ether-β-cyclodextrin and comparatively studying its antifungal efficacy. Results: The nanosuspension had a particle size range of 332.7-779.2nm, zeta potential +0.609-16.3, entrapment efficiency 61.32 ± 1.36%-76.34 ± 2.04%. Ex vitro corneal permeability study showed that optimized itraconazole nanosuspension produced higher permeation as compared to the market formulation and Itraconazole eye drop. Moreover, optimized nanosuspension was found as more active against Candida albicans & Aspergillus flavus compared to the market formulation and Itraconazole eye drop. Conclusion: The nanosuspension approach could be an ideal, promising approach to increase the solubility and dissolution of Itraconazole.

Background: The psychosocial functioning and motivation scales of the Texas Cristian University (TCU) were translated and validated for the Persons Who Use Drugs (PWUDs). Methods: This study was carried out as a methodological research. The scales were translated forward and backward and then, the PWUDs in Kermanshah-based (west of Iran) substance abuse treatment centers in 2019 filled out the scales. Participants included 250 individuals who were selected by convenience sampling method. A demographics form and psychosocial functioning and motivation scales were used to collect data. For data analysis, content validity, face validity, testretest, internal consistency, and construct validity were applied by using exploratory analysis methods in SPSS (v.20) and confirmatory factor analysis in LISREL software. Results: Exploratory Factor Analysis (EFA) results were obtained by using the main component analysis and Varimax rotation of three factors (psychological function, social function, treatment motivation). Extracted factors, along with the eigenvalues, attributed variance percentage, and cumulative attributed variances by each factor, by 68.56%, showed a total variance of the questionnaire. Moreover, the fitness indexes of the Confirmatory Factor Analysis (CFA) of psychological function, social function, and treatment motivation were 0.059, 0.075 and 0.072, respectively. Therefore, the questionnaire fitness was at an acceptable level. The test-retest reliability coefficient was 0.875, and the Cronbach's alpha coefficient for all the components was higher than 0.71. Conclusion: The results showed that psychosocial functioning, motivation scales have good psychometric properties, and they can be used in research and treatment fields.

Background/Objective: To study the therapeutic potential of Antileukotriene drug- Camellia sinensis extract co-formulation on histamine induced asthma in guinea pigs. Methods: SRSD of Montelukast sodium was prepared by the solvent evaporation method. Lyophilized aqueous extract of Camellia sinensis leaves and SRSD mixture was filled in capsule and the capsule shell was coated to achieve initial release lag time. In vitro and pharmacokinetic study of capsules was performed and compared with commercial tablets. A further role of green tea, as an antioxidant adjunct for asthma management, has been analyzed by lung histology, mast cell count and oxidative stress assay in the serum of control and experimental animals. Results: The drug release from the commercial tablet was immediate and rapid, but capsule has shown an initial 3.5 hr lag time followed by sustained action up to 8 hr. Pharmacokinetic results show that studied formulations are bioequivalent with respect to Cmax and AUC, while rest parameters showed asignificant difference. Mast cells count in lung tissue were increased (p<0.001) in the experimental group along with glycoprotein deposition in asthmatic bronchioles. Levels of SOD and GPX were decreased (p<0.05) while CAT was increased (p<0.04) in the asthma group in comparison to control. Conclusion: In the experimental animal model, co-formulation was effective in modulating allergic inflammation and contributing to better control of the inflammatory response. Our findings suggest that Camellia sinensis leaves extract may be used as an adjunct for future improvements in asthma treatment and prevention.

Background: A newer trend has been seen recently to reuse the conventional drugs with distinct indications for the newer applications to speed up the drug discovery and development based on earlier records and safety data. Most of the non-cancerous agents could afford a little or tolerable side effects in individuals. However, the repositioning of these non-cancerous agents for successful anticancer therapy is an outstanding strategy for future anti-cancer drug development. Since more diverse and selective cancer drug targets are being discovered and developed, the approved drug collections are particularly useful to quickly identify clinically advanced anticancer drugs against those targets. Objective: Antihelminthic drugs such as Mebendazole and Albendazole (Benzimidazole class) have been reported to exhibit cytotoxicity (or anticancer activities) against several types of cancer. Therefore, this study aims to repurpose the benzimidazole scaffold for breast cancer treatment. Methods: In the present study, three hydrazone analogs having a benzimidazole motif in their structural frame were synthesized. Their in-silico binding studies against HER2 receptor (PDB ID: 4LQM) and ADMET studies were carried out using Accelrys drug discovery studio 4.1. Cytotoxicity of the synthesized compounds against HER2 overexpressed MCF-7 cell lines was determined by MTT assay. Results: One of the compounds 2-[2-(2,4-dinitrophenyl)hydrazinylidene]-2,3-dihydro-1H-benzimidazole (U1) has shown good cytotoxicity when compared to the standard Lapatinib, which is a well known HER2 inhibitor. Conclusions: Thus, the designed benzimidazole scaffold might serve as the best leads for treating breast cancer, which is additionally confirmed by performing their docking study via Accelrys discovery studio.