Harmeet Kaur

Perspectives of Benzimidazole Derivatives as Anticancer Agents in the New Era.

Cancer is one of the deadliest diseases nowadays and is a great topic for research as the challenging task is to develop new entities with selectivity towards cancerous cells. Heterocyclic compounds are of great importance in medicinal chemistry as they possess an extensive range of therapeutic applications. Benzimidazole is one such important heterocyclic organic compound having structural analogy to nucleotides found in human body and hence is an important pharmacophore in medicinal chemistry. A variety of marketed drugs containing benzimidazole are thiabendazole, flubendazole (anthelmintic), astmizole (antihistaminic), lansoprazole and omeprazole (antiulcerative). In the light of the above facts, this review is an attempt to summarize the collective contributions from the authors around the world in the field of anticancer agents. This review highlights synthetic schemes and anticancer activity results of the research done in the past years.

Polymer Drug Conjugates: Recent Advancements in Various Diseases

During the past decade, the arena of polymer therapeutics has acquired considerable interest and accompanied by advanced designs and chemical properties of polymer-drug conjugates. Various polymers, such as poly (ethylene glycol) (PEG), N-(2-hydroxypropyl) methacrylamide (HPMA), poly(glycolic acid) (PGA) and poly(lactide-co-glycolide) (PLGA) have been used successfully for clinical utilization from decades. These polymers are used in combination of drugs in such a manner that they target the specific tissues and thus the toxicity of drugs to other tissues is reduced. Presently, numerous polymer drug conjugates are under clinical trial for treatment of various diseases including cancer, diabetes, AIDS, rheumatoid arthritis etc. Many protein-polymer conjugates have been approved by FDA for clinical use but till date, no polymer-synthetic drug conjugate is approved by FDA, although many of them are undergoing final phase of clinical trials. This review highlights the recent advancements in the polymer-drug conjugates for treatment of various diseases and their preclinical and clinical status.

Polymer Particulates in Drug Delivery

Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily tuned by precisely engineering the constituent blocks of polymers for improving drug loading, release rate, pharmacokinetics, targeting, etc. The end-groups of various polymers can be readily modified with ligands making them suitable for recognizing by cell-specific receptors, providing cellular specificity, and superior intracellular delivery. This review will mainly cover delivery of many potential drugs and biomolecules by means of polymeric microparticles, nanoparticles and copolymer micelles or assemblies. An overview about formulation methods of polymer particulates has also been addressed. Attempt has been made to cover all the potential polymers that are well known in pharmaceutical history.

Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery.

New polymer therapeutics like polymer-drug conjugates (PDCs) are developing day by day. Heterocyclic drugs with excellent cytotoxic properties are available, but lack of their specificity makes them available to the normal cells also, which is the main cause of their toxicity. Drugs in the form of PDCs make delivery possible to the specific sites. Most of the PDCs are designed with the aim to either target and/or to get activated in specific cancer microenvironments. Therefore, the most exploited targets for cancer drug delivery are; cancer cell enzymes, heat shock protein 90 (HSP90), multi-drug resistance (MDR) proteins, angiogenesis, apoptosis and cell membrane receptors (e.g., folates, transferrin, etc.). In this review, we will summarize PDCs of heterocyclic drugs, like doxorubicin (DOX), daunorubicin, paclitaxel (PTX), docetaxel (DTX), cisplatin, camptothecin (CPT), geldanamycin (GDM), etc., and some of their analogs for efficient delivery of drugs to cancer cells.

Diazenyl Derivatives and their Complexes as Anticancer Agents

In the past years, many diazenyl compounds (i.e diazenecarboxamides, diazeniumdiolate prodrugs, diazenyl complexes etc.) have been prepared for the evaluation of their cytotoxic potential towards various cancer cell lines. Majority of them have shown promising cytotoxic activities even against several drug resistant cell lines. These derivatives have shown their effect by acting as alkylating agents, releasers of cytotoxic NO, targeting receptors like tyrosine kinase, EGFR or targeting enzymes like GST, AGT, CDKs etc. Their interaction with different receptors or enzymes leads to DNA damage, necrosis or apoptosis resulting in cell death. The present review will cover updated information on the synthetic methodologies and cytotoxic potential of diazenyl derivatives developed during the past years along with the recent developments. This may prove to be helpful for the researchers to develop novel anticancer drugs in future by molecular modifications of potential derivatives with better cytotoxic activities.

Development of novel gastroretentive salbutamol sulfate-loaded sodium alginate-pectin bubble beads prepared by co-axial needle air-injection method and in vivo clinical evaluation by ultrasound studies

&NA; In the present study, the salbutamol sulfate‐loaded sodium alginate‐pectin (SS‐loaded SA‐PEC) bubble beads have been optimized and evaluated for drug loading, in vitro drug release, in vivo floating behavior in the stomach, etc. Nine batches (F1–F9) of bubble beads with different SA and PEC contents were prepared by novel co‐axial needle air‐injection method and related to their percent drug loading efficiency (%DLE) and percent drug release at 4 h (%R4h) as response factors. The multivariate analysis has shown the effect of SA/PEC ratio, total polymer content, as well as their interaction on %DLE and %R4h. In the quantitative modeling, the satisfactory adjustment of the linear models (along with interaction terms) with the experimental data for both %DLE and %R4h has confirmed the findings of the multivariate analysis. The optimized SS‐loaded SA‐PEC bubble beads based on 2D (contours), 3D, desirability, and overlay plots has exhibited %DLE of 87.35 ± 2.48% (n = 3 and error = 2.94%) and %R4h of 85.79 ± 2.98% (n = 3 and error = 0.25%). The in vitro drug release studies have shown almost complete (≥85%) SS release from all the batches within 4–6 h in simulated gastric fluid (SGF) pH 1.2. The in vivo clinical findings by ultrasound studies have shown excellent floatation (>6 h) behavior of bubble beads in the upper gastrointestinal tract (GIT) and efficient stomach‐specific gastroretention. Graphical abstract Figure. No caption available.

Editorial: The Need of Time: Development of New Antimicrobials

The discovery and application of antimicrobial drugs in therapy has undoubtedly contributed to the control of mortality from infectious diseases. But they still have a significant place as a cause of death and are immediately followed by neoplasms, heart disease, cerebrovascular events and other complications. Many years after the discovery of antibiotics, microbial infections have again become a threat to the mankind. The antibiotic resistance crisis has been accredited to the unregulated use of drugs, prescription recklessness, food-chain contamination, lack of new drug development by the pharmaceutical industry due to reduced economic incentives and challenging regulatory requirements with Antimicrobial Resistance (AMR) even being ranked as bioterrorism. The all responsibility lies on the researchers to develop new classes of antibiotic to challenge the global crisis of increasing Antimicrobial Resistance (AMR). During recent years, few new antibiotics become available against Gram-positive bacteria but no new class of antibiotic for Gram-negative infections has been discovered for more than 40 years. Thus there is an urgent need to design new agents with different mode of action in order to overcome the cross-resistance with the present therapeutics. It is clear that outstripping AMR emphasizes on the need of thorough understanding of resistance mechanisms, scientific ingenuity, novel ideas and practical applicability of these ideas across the clinical spectrum. This thematic issue will cover several key aspects deal with this important issue.

A simple 2D composite image analysis technique for the crystal growth study of l‐ascorbic acid

This work was destined for 2D crystal growth studies of L‐ascorbic acid using the composite image analysis technique. Growth experiments on the L‐ascorbic acid crystals were carried out by standard (optical) microscopy, laser diffraction analysis, and composite image analysis. For image analysis, the growth of L‐ascorbic acid crystals was captured as digital 2D RGB images, which were then processed to composite images. After processing, the crystal boundaries emerged as white lines against the black (cancelled) background. The crystal boundaries were well differentiated by peaks in the intensity graphs generated for the composite images. The lengths of crystal boundaries measured from the intensity graphs of composite images were in good agreement (correlation coefficient “r” = 0.99) with the lengths measured by standard microscopy. On the contrary, the lengths measured by laser diffraction were poorly correlated with both techniques. Therefore, the composite image analysis can replace the standard microscopy technique for the crystal growth studies of L‐ascorbic acid.

Kozeny–Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets

Abstract This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability kperm based on Kozeny–Carman equation. Batches (L1–L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The kperm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants kd. Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3–L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI95%) revealed significant differences between kd values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f2) test. The final relationship between kd and kperm was found to be hyperbolic, signifying the initial effect of kperm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between kd and kperm. The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

Diazenyl derivatives as therapeutic and diagnostic agents acting on central nervous system.

In last decade, the development of new drugs and drug products for central nervous system (CNS) has remained limited due to incomplete elucidation of pathophysiology of many CNS disorders, complexity of the diseases and the lack of technologies for delivery through the blood-brain barrier (BBB). In this article we will summarize the development of diazenyl derivatives of many biologically active moieties like benzodiazepine, formazan, indole, pyrimidine, thiazole, sulfonamide etc. as diagnostic and therapeutic agents for CNS. The potential of already existing azo compounds as potent CNS agents have also been discussed. This overview will provide the researchers an opportunity for further development of new diazenyl derivatives in CNS area.