Current Pharmaceutical Design - Volume 26, Issue 38, 2020

Cocrystallization of specific active pharmaceutical ingredients (APIs) in the solid-state phase is becoming a feasible way to improve their corresponding physicochemical properties and ultimate bioavailability without making and breaking any covalent bonds within them. Many recent reports deal with the characterization and analysis topics of pharmaceutical APIs-based cocrystals. In this mini-review, we will focus on the recent steady-state and time-dependent spectroscopic investigation into the cocrystallization of specific APIs based on both Raman and emerging terahertz spectroscopy in pharmaceutical fields. Distinctive spectral, structural and also kinetic information of pharmaceutical APIs-based cocrystals are obtained and discussed, which would highlight the potential of vibrational spectroscopy as an attractive technique for various drug research and development during cocrystallization of specific APIs.

Azoles are a family of five-membered azacyclic compounds with relevant biological and pharmacological activity. Different subclasses of azoles are defined depending on the atomic arrangement and the number of nitrogen atoms present in the ring: pyrazoles, indazoles, imidazoles, benzimidazoles, triazoles, benzotriazoles, tetrazoles and pentazoles. The complete characterization of their structure and the knowledge about their crystal packing and physical and chemical properties are of vital importance for the advancement in the design of new azole-containing drugs. In this review, we report the latest recent contributions to azole chemistry, in particular, those in which theoretical studies have been performed.

Cocrystallization is a widely accepted and clinically relevant technique that has prospered very well over the past decades to potentially modify the physicochemical properties of existing active pharmaceutic ingredients (APIs) without compromising their therapeutic benefits. Over time, it has become an integral part of the pre-formulation stage of drug development because of its ability to yield cocrystals with improved properties in a way that other traditional methods cannot easily achieve. Cocrystals are solid crystalline materials composed of two or more than two molecules which are non-covalently bonded in the same crystal lattice. Due to the continuous efforts of pharmaceutical scientists and crystal engineers, today cocrystals have emerged as a cutting edge tool to modulate poor physicochemical properties of APIs such as solubility, permeability, bioavailability, improving poor mechanical properties and taste masking. The success of cocrystals can be traced back by looking at the number of products that are getting regulatory approval. At present, many cocrystals have obtained regulatory approval and they successfully made into the market place followed by a fair number of cocrystals that are currently in the clinical phases. Considering all these facts about cocrystals, the formulation scientists have been inspired to undertake more relevant research to extract out maximum benefits. Here in this review cocrystallization technique will be discussed in detail with respect to its background, different synthesis approaches, synthesis mechanism, application and improvements in drug delivery systems and its regulatory perspective.

Background: MicroRNA-126, a microRNA implicated in blood vessel integrity and angiogenesis is significantly up/down regulated in different physiological and pathological conditions related to angiogenesis such as cardiovascular formation and angiogenesis dependent diseases. MicroRNA-126 plays a critical role in angiogenesis via regulating the proliferation, differentiation, migration, and apoptosis of angiogenesis related cells such as endothelial cells. Objective: The aim of this review is to investigate the molecular mechanisms and the effects of microRNA-126 on the process of angiogenesis in pathophysiological conditions. Methods: To conduct this review, related articles published between 2001 and 2019 were collected from the PubMed, Web of Science, Google Scholar, Scopus and Scientific Information Database using search terms such as microRNA-126, angiogenesis, cardiovascular disorders, hypoxia, VEFG-A, endothelial cells, VEGF pathway, and gene silencing. Then, the qualified articles were reviewed. Results: MicroRNA-126 regulates the response of endothelial cells to VEGF, through directly repressing multiple targets, including Sprouty-related EVH1 domain-containing protein 1 (SPRED1) and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-b). MicroRNA-126 -3p and microRNA-126 -5p have cell-type and strandspecific functions and also various targets in angiogenesis that lead to the regulation of angiogenesis via different pathways and consequently diverse responses. Conclusion: MicroRNA-126 can bind to multiple targets and potentially be both positive and negative regulators of gene expression. Thus, microRNA-126 could cause the opposite biological effects depending on the context. As a result, understanding the different cellular pathways through which microRNA-126 regulates angiogenesis in various situations is a critical aspect in the development of novel and effective treatments for diseases with insufficient angiogenesis.

Background: Any sort of wound injury leads to skin integrity and further leads to wound formation. Millions of deaths are reported every year, which contributes to an economical hamper world widely, this accounts for 10% of death rate that insight into various diseases. Current Methodology: Rapid wound healing plays an important role in effective health care. Wound healing is a multi-factorial physiological process, which helps in the growth of new tissue to render the body with the imperative barrier from the external environment. The complexity of this phenomenon makes it prone to several abnormalities. Wound healing, as a normal biological inherent process occurs in the body, which is reaped through four highly defined programmed phases, such as hemostasis, inflammation, proliferation, and remodeling and these phases occur in the proper progression. An overview, types, and classification of wounds along with the stages of wound healing and various factors affecting wound healing have been discussed systematically. Various biopolymers are reported for developing nanofibers and microfibers in wound healing, which can be used as a therapeutic drug delivery for wound healing applications. Biopolymers are relevant for biomedical purposes owing to biodegradability, biocompatibility, and non- toxicity. Biopolymers such as polysaccharides, proteins and various gums are used for wound healing applications. Patents and future perspectives have been given in the concluding part of the manuscript. Overall, applications of biopolymers in the development of fibers and their applications in wound healing are gaining interest in researchers to develop modified biopolymers and tunable delivery systems for effective management and care of different types of wounds.

For improvisation of diabetic’s quality of life, nanotechnology is facilitating the development of advanced glucose sensors as well as efficient insulin delivery systems. Our prime focus of the review is to highlight the advancement in diabetic research with special reference to nanotechnology at its interface. Recent studies are more focused on enhancing sensitivity, accuracy, and response by employing metal as well as nanoparticles based glucose sensors. Moreover, the review focuses on nanoscale based approaches i.e. closed-loop insulin delivery systems, which detect any fluctuation in blood glucose levels and allow controlled release of a drug, thus are also called self-regulating insulin release system. Additionally, this review summarizes the role of nanotechnology in the diagnosis and treatment of diabetic complications through little advancement in the existing techniques. To improve health, as well as the quality of life in diabetic’s new sensing systems for blood glucose level evaluation and controlled administration of drugs through efficient drug delivery systems should be explored.

It has been well established that solid dispersions have a high potential to increase the release rate of poorly water-soluble drugs, resulting in high drug bioavailability. Solid dispersions have been vigorously investigated with various practical approaches in recent decades. Improvements in wettability, molecular interactions and drugs being held in an amorphous state in solid dispersions are the main mechanisms underlying the high drug release rate. Moreover, the synergistic effect of incorporating nanotechnology in solid dispersions is expected to lead to an advanced drug delivery system for poorly water-soluble drugs. However, to date, there is still a lack of reviews providing outlooks on the nano-sized solid dispersions that have been substantially investigated for improving the bioavailability of poorly water-soluble drugs. In the current review, we aim to overview key advantages and approaches for producing nano-sized solid dispersions. The classification of key strategies in developing nano-sized solid dispersions will advance the creation of even more efficient solid dispersions, which will translate into clinical studies.

Background: Total hip replacement (THR) is the standard surgical treatment of hip diseases. Periprosthetic bone mass density (BMD) loss may be a cause for revision surgery. Bisphosphonates (BPs) are now the principal class medications for osteoporosis. Objective: To demonstrate the effect of BPs on treating periprosthetic osteoporosis after THR via a meta-analysis of randomized controlled trials (RCTs). Methods: A comprehensive search of PubMed, EMBASE, the Web of Science and the Cochrane Central Register of Controlled Trials was performed for RCTs on the effect of BPs on treating periprosthetic osteoporosis after THR and clinical outcomes relative to controls. The primary outcome measures were the change in BMD in each region of interest (ROI), the change in serum bone turnover marker levels, the change in functional parameters and the risk of adverse effects (AEs). The final search was performed in March, 2020. Results: Nine RCTs were included. A total of 359 patients met the inclusion criteria. BPs can clearly maintain periprosthetic BMD in ROIs at 1, 2, 3, 4, 6 and 7 at 6, 12 and 24 months. In addition, BPs can clearly decrease serum procollagen type 1 N-terminal propeptide (P1NP) levels at 12 months. There was no significant difference in the risk of AEs between the BP and control groups; however, BPs can cause more patients to decline participation. Conclusion: BPs can effectively maintain overall periprosthetic BMD, but BMD in ROI 5 remains controversial. In addition, the safety of BPs is relatively high, but the compliance may be relatively low.

Background: Histone deacetylase (HDAC) inhibition has been found to be effective in the treatment of inflammatory bowel disease. Previous studies have reported that Cinnamyl sulfonamide hydroxamate derivatives possess non-selective HDAC inhibition. Objective: The present study was designed to screen three selected Cinnamyl sulfonamide hydroxamate derivatives, NMJ-1, NMJ-2, and NMJ3, for in vitro anti-inflammatory response by assessing the expression of pNF-ΚB in lipopolysaccharide (LPS)-induced inflammatory changes on RAW 264.7 cells, and in vivo anti-inflammatory response in acetic acid (AA) and 2.4-dinitrochlorobenzene (DNCB)-induced colitis models in Wistar rats. Method: AA-induced colitis was produced in Wistar rats by intra-colonic administration of 1 ml AA. DNCBinduced colitis was produced by spraying 250 μL DNCB in acetone (20g/L) on the nape of the rats for 14 days, followed by the intracolonic administration on day 15. Drugs were administered for three days after the induction of colitis. Results: In vitro anti-inflammatory effect was observed by NMJ1 and NMJ2 through a significant decrease in pNF-ΚB overexpression-induced by LPS. Similar effect was observed in anti-colitis response by NMJ2 in both models by reversing the colitis-induced changes in length, weight, anti-oxidant profile and histopathology of the colon. Conclusion: NMJ2 was found to be most effective among the tested compounds as an anti-inflammatory agent in both in vitro and in vivo inflammatory studies.

Objective: Our aim was to detect the effects of DNA methylations in the phosphoethanolamine/ phosphocholine phosphatase (PHOSPHO1) gene on the therapeutic efficacy of simvastatin. Methods: We used an extreme sampling approach by selecting 211 individuals from approximately the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n=104 for the high response group and n=107 for the low response group) from a total of 734 subjects with hyperlipidemia. They received a daily oral dose of 20 mg simvastatin for eight consecutive weeks. DNA methylation loci at the PHOSPHO1 gene were measured using high-throughput next-generation sequencing-based sequencing technology. Fasting serum lipids were measured at baseline and after eight weeks of simvastatin treatment. Results: Mean PHOSPHO1 DNA methylation had a significant negative correlation with high-density lipoprotein cholesterol (HDL-C) variation (β=-0.014, P=0.045) in the high response group. After stratifying by body mass index (BMI), the associations between the PHOSPHO1 DNA methylations and the change in HDL-C in response to simvastatin were more significant in obese subjects with a BMI of 25 kg/m2 or higher (β=-0.027, P=0.002). Mean PHOSPHO1 methylation and traditional predictors could explain up to 24.7% (adjusted R2) of the change in HDL-C response in obese patients. There was a statistically significant additive interaction term (P=0.028) between BMI and mean PHOSPHO1 methylation in the model of the change in HDL-C in response to simvastatin. Conclusion: Our findings suggest that PHOSPHO1 DNA methylations are associated with a change in HDL-C in response to simvastatin treatment, and this association is especially dependent on the extent of patient obesity.