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Reports on a significant positive correlation between consumption of carotenoid-rich food and prevention of Alzheimer's disease (AD) led to the investigation of carotenoids for the treatment and prevention of AD. More than 1100 types of carotenoids are found naturally, out of which only around 50 are absorbed and metabolized in human body. Lycopene is one of the most commonly ingested members of fat-soluble carotenoid family that gives vegetables and fruits their red, yellow, or orange color. Lycopene has established itself as a promising therapy for AD owing to its neuroprotective activities, including antioxidant, anti-inflammatory, and antiamyloidogenic properties. In this review, we highlight the various in vitro and preclinical studies demonstrating the neuroprotective effect of lycopene. Also, some epidemiological and interventional studies investigating the protective effect of lycopene in AD have been discussed. Diving deeper, we also discuss various significant mechanisms, through which lycopene exerts its remissive effects in AD. Finally, to overcome the issue of poor chemical stability and bioavailability of lycopene, some of the novel delivery systems developed for lycopene have also been briefly highlighted.

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.

Abstract: Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of the investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan, and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.

Coronavirus disease 2019 (COVID-19), which emerged as a major public health threat, has affected400 million people globally leading to5 million mortalities to date. Treatments of COVID-19 are still to be developed as the available therapeutic approaches are not able to combat the virus causing the disease (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) satisfactorily. However, antiviral peptides (AVPs) have demonstrated prophylactic and therapeutic effects against many coronaviruses (CoVs).This review critically discusses various types of AVPs evaluated for the treatment of COVID-19 along with their mechanisms of action. Furthermore, the peptides inhibiting the entry of the virus by targeting its binding to angiotensin-converting enzyme 2 (ACE2) or integrins, fusion mechanism as well as activation of proteolytic enzymes (cathepsin L, transmembrane serine protease 2 (TMPRSS2), or furin) are also discussed.Although extensively investigated, successful treatment of COVID-19 is still a challenge due to emergence of virus mutants. Antiviral peptides are anticipated to be blockbuster drugs for the management of this serious infection because of their formulation and therapeutic advantages. Although they may act on different pathways, AVPs having a multi-targeted approach are considered to have the upper hand in the management of this infection.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Several conventional treatments for UC such as corticosteroids, immunosuppressive agents, tumor necrosis factor antagonist, integrin blockers, and interleukin antagonist, and salicylates are available but are associated with the various limitations and side-effects. None of the above treatments helps to achieve the ultimate goal of the therapy, i.e., maintenance of remission in the long-term. Natural remedies for the treatment of UC show comparatively less side effects as compared to conventional approaches, and affordable. The current review presents details on the role of herbal drugs in the treatment and cure of UC. Google, PubMed, Web of Science, and Scopus portals have been searched for potentially relevant literature to get the latest developments and updated information related to use of natural drugs in the treatment of UC. Natural products have been used over centuries to treat UC. Some of the essential herbal constituents exhibiting antiulcerogenic activity include gymnemic acid (Gymnema sylvestre), shagoal (Zingiber officinale), catechin (Camellia sinensis), curcumin (Curcuma longa), arctigenin (Arctium lappa), and boswellic acid (Boswellia serrata). Although many plant-derived products have been recommended for UC, further research to understand the exact molecular mechanism is still warranted to establish their usefulness clinically.

Background Inflammation, an important event of cellular defensive system, can be triggered by a variety of factors such as pathogens, allergens, damaged cells and toxic compounds. Inflammation indicates tissue remodeling and repair, and is characterized by redness, heat, swelling, pain and loss of function. Purpose Conventional treatment approaches for treatment of inflammation/mediated disorders are associated with various side effects. Herbal remedies are comparatively safe with few side effects. Therefore, the current review summarizes different phytoconstituents which have exhibited their anti-inflammatory potential in various preclinical studies. Methods Google, PubMed, Web of Science and Scopus database have been searched for potentially relevant literature on plant based anti-inflammatory agents. Search was performed using different key words such as “inflammation”, “herbal drugs”, “anti-inflammatory drugs”, “phytomedicine for inflammation” and “plant derived drugs for inflammation”. Further studies were screened through assessment of abstracts and previously published review articles. Results A number of natural products are reported to exhibit anti-inflammatory property in various preclinical and clinical studies and some of them are currently available as herbal formulations. Prominent phytoconstituents exhibiting anti-inflammatory activity include shagoal (Zingiber officinale Roscoe), curcumin (Curcuma longa L.), boswellic acid (Boswellia serrata Roxb.), quercetin (Allium cepa L.), rosmarinic acid (Rosmarinus officinalis L.), berberine (Coptis chinensis Franch) and catechin (Camellia sinensis (L.) Kuntze). Conclusion Phytoconstituents have been reported to exhibit anti-inflammatory property by targeting enzymes and modulating inflammatory mediators and/or by other pathways. Although various preclinical studies have demonstrated promising results against inflammation, however, further research is required to ensure their safety and efficacy in human beings.

Background: Chrysin, a flavonoid, occurs naturally in plants and possesses many pharmacological actions, but there is a lack of suitable analytical methods for its estimation. Objective: To develop a simple analytical method and validate it for the estimation of chrysin using reverse phase high-performance liquid chromatography (RP-HPLC). objective: To develop a simple analytical method and validate it for estimation of Chrysin using reverse phase high performance liquid chromatography (RP-HPLC). Methods: Isocratic elution was carried out in methanol and 0.1% v/v formic acid in a 70:30 ratio using a C-18 reverse-phase column. The flow rate was set to 1 mL min-1 and the detection wavelength at 268 nm. As per ICH Q2 (R1) guidelines, the developed method was validated in terms of accuracy, precision, system suitability, and robustness. method: Isocratic elution was carried out in methanol and 0.1% v/v formic acid in 70:30 ratio using C-18 reverse-phase column. The flow rate was set to 1 mL min-1 and detection wavelength at 268 nm. As per ICH Q2 (R1) guidelines, the developed method was validated in terms of accuracy, precision, system suitability and robustness. Results: The retention time of Chrysin was found at 10.269 min. In the concentration range of 2-10 g/mL, the developed method was linear with a regression coefficient (R2) value of 0.998. The mean percentage recovery of chrysin was found within 95-105% at all three levels, which confirms that the developed method was accurate. Moreover, the % RSD was found to be less than 2% confirming that the developed method was precise. The limit of detection and limit of quantification were found to be 0.071 and 0.217 µg/mL. Moreover, the validated method was robust with no significant changes in response to variation in flow rate, mobile phase composition, wavelength, and different lots of columns. Conclusion: It was concluded that the developed method has passed all validation tests and was successfully applied to estimate the presence of Chrysin in bulk as well as in pharmaceutical formulations. conclusion: It was concluded that the developed method has passed all the validation tests and successfully applied to estimate the presence of Chrysin in bulk as well as in pharmaceutical formulations.

Huntington’s disease (HD) is an autosomal fatal genetic disease in which degeneration of neuronal cells occurs in the central nervous system (CNS). Commonly used therapeutics are cludemonoamine depletors, antipsychotics, antidepressants, and tranquilizers. However, these drugs cannot prevent the psychotic, cognitive, and behavioral dysfunctions associated with HD. In addition to this, their chronic use is limited by their long-term side effects. Herbal drugs offer a plausible alternative to this and have shown substantial therapeutic effects against HD. Moreover, their safety profile is better in terms of side effects. However, due to limited drug solubility and permeability to reach the target site, herbal drugs have not been able to reach the stage of clinical exploration. In recent years, the paradigm of research has been shifted towards the development of herbal drugs based nanoformulations that can enhance their bioavailability and blood-brain barrier permeability. The present review covers the pathophysiology of HD, available biomarkers, phytomedicines explored against HD, ongoing clinical trials on herbal drugs exclusively for treating HD and their nanocarriers, along with their potential neuroprotective effects.

Background Peptic ulcer (PU) is a collective term used for a group of chronic manifestations that affect mucosal integrity of stomach and/or duodenal lining. It is characterized by pain, perforations, bloating, nausea, blood in stool or vomit, loss of appetite and weight loss. Purpose Although a number of conventional treatment approaches such as antihistaminics, proton pump inhibitors, prostaglandins, antacids and antimicrobial agents are available for the management of PU, but they all are associated with various side effects. Herbal drugs are alternative remedies for the treatment of various pharmacological conditions and are generally considered to be much safer as compared to synthetic drugs. The present review summarizes the different phytoconstituents that have been explored for their antiulcer potential in various preclinical studies. Methods Literature search was conducted across four electronic databases (Google, PubMed, Web of Science and Scopus) for potentially relevant literature. Search was performed using various key words such as “peptic ulcer”, “herbal drugs”, “anti-ulcer”, “anti-ulcer plants”, “phytomedicine for peptic ulcer”, and “plant derived drugs for peptic ulcer”. Further studies were screened through examination of abstracts, reference sections and well on the basis of previously published review articles. Results A number of natural products are reported to exhibit antiulcer property in various animal studies and some of them are currently being used in various herbal formulations. Prominent phytoconstituents exhibiting anti-ulcerogenic activity include friedelin (Maytenus robusta Reissek); squalene (Muntingia calabura L.); brasiliensic acid (Calophyllum brasiliense Cambess.); shogaol (Zingiber officinale Roscoe); allitridin (Allium sativum L.); rutin (Stryphnodendron rotundifolium Mart.); ligustilide (Angelica sinensis (Oliv.) Diels); curcumin (Curcuma longa L.); and rosmarinic acid (Ocimum tenuiflorum L.). Conclusion Phytoconstituents have been reported to exhibit antiulcer property by targeting various enzymes, inflammatory mediators and/or by other pathways. Although they have shown promising results in preclinical studies, however, further research is required to ensure their safety and efficacy in human beings.

Background Capsiate is a non-pungent analogue of capsaicin. Consumed worldwide, capsiate hitherto remains unexplored despite its proven track record as a food ingredient and recent use for its therapeutic profile. Though possessing a much better safety profile and an equivalent therapeutic potential, the molecule has not been extensively explored in scientific research pertaining to either food or therapeutic sciences. Scope and approach This comprehensive review summarizes the studies demonstrating the therapeutic potential of capsiate in various pathological conditions. The mechanistic pathways for these pharmacological activities are also deliberated upon. Discussed also are various patents that have been filed for various innovative uses of capsiate. Key findings and conclusions The molecule has been successfully explored in treatment of obesity, metabolic disorders, cancer, cardiovascular disorders and gastro-intestinal disorders. It, however, faces the challenge of low aqueous solubility and stability. The lack of popularity of this immensely useful therapeutic nutraceutical probably accrues from these two factors. Designing an effective dosage form with complete absence of water is a challenge in itself. The capsules available in the market for its anti-obesity effect are also oily in nature. The challenge further intensifies when topical delivery across the mucous membrane of skin is targeted. The approaches that may be used for exploration of this drug in conditions like weight management, cancer, pain, diabetes, dysphagia, skin diseases and muscle atrophy include solid lipid nanoparticles, polymer nanoparticles, dendrimers, non-aqueous nanoemulsions and even liquid/solid self-nanoemulsifying drug delivery systems that may be reconstituted at the time of injection.

With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.

In recent years, unique physicochemical properties of amphiphilic block copolymers have been utilized to design the polymeric micelles for brain-specific delivery of drugs, proteins, peptides and genes. Their unique properties such as nano-size, charge-switching ability, stimuli-responsive cargo release, flexible structure, and self-assembly enable them to overcome limitations of conventional dosage forms that include rapid drug release, drug efflux, and poor brain bioavailability, and poor stability. These limitations hinder their therapeutic efficacy in treating brain diseases. Their ease of functionalization and enhanced penetration and retention effect make them suitable nanocarriers for the diagnosis of various brain diseases. In this context, the present manuscript provides an insight into the progress made in the functionalization of micelles such as the incorporation of stimuli-sensitive moieties in copolymers, conjugation of cargo molecules with the core-forming block via responsive smart linkers, and conjugation of active ligands and imaging moieties with the corona forming block for brain targeting and imaging. Further, the review also expounds on the role of polymeric micelles in delivering neurotherapeutic to the brain. Some patents related to polymeric micelles formulated for brain delivery are also enlisted.

Abstract: Metabiotics have emerged as the safer alternatives to probiotics in last decade. Unlike probiotics that are live microbes, metabiotics are the low molecular weight bioactive metabolites produced by the gut microbiota. While offering a similar profile of health benefits as that of probiotics, metabiotics are free from the risks and uncertain responses associated with administration of live bacteria into the body. Metabiotics have demonstrated substantial effectiveness across the ethnicities, age, gender and nutritional habits in a number of metabolic disorders, including obesity. Obesity is attributed to the offsetting of the energy homeostasis of the body due to a number of genetic, endocrinological, and environmental factors leading to obesity. The obesogenic mechanisms are quite complicated as they result from a complex interplay among a number of factors. Owing to a variety of constituents exerting their action through different pathways, metabiotics offer a pragmatic option for treatment as well as prevention of obesity by addressing heterogeneous aspects of its aetiology. In this review, we categorize various components of metabiotics and discuss their cross-talk with host cells at the molecular level. We also discuss the challenges in understanding these interactions and their potential effects on obesity treatment and prevention strategies. Considering the alarming rise in obesity all over the world, metabiotics offer an attractive non-pharmacological approach to spearhead the strategies being designed to combat the challenges posed by the obesity epidemic.

IntroductionNon-aqueous nano-emulsions (NANEs) are colloidal lipid-based dispersions with nano-sized droplets formed by mixing two immiscible phases, none of which happens to be an aqueous phase. Their ability to incorporate water and oxygen sensitive drugs without any susceptibility to degradation makes them the optimum dosage form for such candidates. In NANEs, polar liquids or polyols replace the aqueous phase while surfactants remain same as used in conventional emulsions. They are a part of the nano-emulsion family albeit with substantial difference in composition and application.Areas coveredThe present review provides a brief insight into the strategies of loading water-sensitive drugs into NANEs. Further advancement in these anhydrous systems with the use of solid particulate surfactants in the form of Pickering emulsions is also discussed.Expert opinionNANEs offer a unique platform for delivering water-sensitive drugs by loading them in anhydrous formulation. The biggest advantage of NANEs vis-à-vis the other nano-cargos is that they can also be prepared without using equipment-intensive techniques. However, the use of NANEs in drug delivery is quite limited. Looking at the small number of studies available in this direction, a need for further research in this field is required to explore this delivery system further.

The aim of present study was to introduce the role of quality by design to produce curcumin crystals with enhanced dissolution rate and bioavailability. The liquid antisolvent method was used to pr...

The role of mushroom polysaccharides and probiotics as pharmaceutical excipients for development of nanocarriers has never been explored. In the present study an attempt has been made to explore Ganoderma lucidum extract powder (GLEP) containing polysaccharides and probiotics to convert liquid self nanoemulsifying drug delivery system (SNEDDS) into solid free flowing powder. Two lipophilic drugs, curcumin and quercetin were used in this study due to their dissolution rate limited oral bioavailability and poor permeability. These were loaded into liquid SNEDDS by dissolving them into isotropic mixture of Labrafill M1944CS, Capmul MCM, Tween-80 and Transcutol P. The liquid SNEDDS were solidified using probiotics and mushroom polysaccharides as carriers and Aerosil-200 as coating agent. The solidification was carried out using spray drying process. The process and formulation variables for spray drying process of liquid SNEDDS were optimized using Box Behnken Design to attain required powder properties. The release of both drugs from the optimized spray dried (SD) formulation was found to be more than 90%, whereas, it was less than 20% for unprocessed drugs. The results of DSC, PXRD and SEM, showed that the developed L-SNEDDS preconcentrate was successfully loaded onto the porous surface of probiotics, mushroom polysaccharides and Aerosil-200.

Microfluidic chip technology is an emerging tool in the field of biomedical application. Microfluidic chip includes a set of groves or microchannels that are engraved on different materials (glass, silicon, or polymers such as polydimethylsiloxane or PDMS, polymethylmethacrylate or PMMA). The microchannels forming the microfluidic chip are interconnected with each other for desired results. This organization of microchannels trapped into the microfluidic chip is associated with the outside by inputs and outputs penetrating through the chip, as an interface between the macro- and miniature world. With the help of a pump and a chip, microfluidic chip helps to determine the behavioral change of the microfluids. Inside the chip, there are microfluidic channels that permit the processing of the fluid, for example, blending and physicochemical responses. Microfluidic chip has numerous points of interest including lesser time and reagent utilization and alongside this, it can execute numerous activities simultaneously. The miniatured size of the chip fastens the reaction as the surface area increases. It is utilized in different biomedical applications such as food safety sensing, peptide analysis, tissue engineering, medical diagnosis, DNA purification, PCR activity, pregnancy, and glucose estimation. In the present study, the design of various microfluidic chips has been discussed along with their biomedical applications.

Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.

Capsiate is a non-pungent analogue of capsaicin. It belongs to the family of capsinoids which are esters of vanillyl alcohol with fatty acids while capsaicin belongs to the family of capsaicinoids that are amides of vanillylamine with a variety of branched-chain fatty acids. While capsaicin is extensively reported for plethora of pharmacological actions, capsiate remains much less explored. Extracted from various species of Capsicum plant, the molecule has also been chemically synthesized via a number of synthetic and enzymatic routes. Based on its action on transient receptor potential vanilloid subfamily member 1 receptors, recent research has focused on its potential roles in treatment of obesity, metabolic disorders, cancer, cardiovascular disorders and gastro-intestinal disorders. Its toxicity profile has been reported to be much safe. The molecule, however, faces the challenge of low aqueous solubility and stability. It has been commercialized for its use as a weight loss supplement. However, the therapeutic potential of the compound which is much beyond boosting metabolism remains unexplored hitherto. This comprehensive review summarizes the studies demonstrating the therapeutic potential of capsiate in various pathological conditions. Discussed also are potential future directions for formulation strategies to develop efficient, safe and cost-effective dosage forms of capsiate to explore its role in various disease conditions. The databases investigated include Cochrane library, Medline, Embase, Pubmed and in-house databases. The search terms were "capsiate," "capsinoids," "thermogenesis," and their combinations. The articles were screened for relevance by going through their abstract. All the articles pertaining to physicochemical, physiological, pharmacological and therapeutic effects of capsiate have been included in the manuscript.

Amphiphilic block copolymers are widely utilized in the design of formulations owing to their unique physicochemical properties, flexible structures and functional chemistry. Amphiphilic polymeric micelles (APMs) formed from such copolymers have gained attention of the drug delivery scientists in past few decades for enhancing the bioavailability of lipophilic drugs, molecular targeting, sustained release, stimuli-responsive properties, enhanced therapeutic efficacy and reducing drug associated toxicity. Their properties including ease of surface modification, high surface area, small size, and enhanced permeation as well as retention (EPR) effect are mainly responsible for their utilization in the diagnosis and therapy of various diseases. However, some of the challenges associated with their use are premature drug release, low drug loading capacity, scale-up issues and their poor stability that need to be addressed for their wider clinical utility and commercialization. This review describes comprehensively their physicochemical properties, various methods of preparation, limitations followed by approaches employed for the development of optimized APMs, the impact of each preparation technique on the physicochemical properties of the resulting APMs as well as various biomedical applications of APMs. Based on the current scenario of their use in treatment and diagnosis of diseases, the directions in which future studies need to be carried out to explore their full potential are also discussed.

Ganoderma lucidium extract powder (GLEP) contains various polysaccharides which are well known for their antioxidant and anti-inflammatory actions. Probiotics (PB) are well-established for providing a plethora of health benefits. Hence, use of mushroom polysaccharides and probiotics as carriers to solidify liquisolid formulation is anticipated to function as functional excipients i.e. as adsorbent that may provide therapeutic benefits. Quercetin (QUR) has been used as model lipophilic drug in this study. QUR loaded liquisolid compacts (LSCs) were formulated using Tween 80 as solvent. These were further solidified using a combination of PB and GLEP as carriers. Aerosil-200 (A-200) was used as coating agent. The formulation exhibited very good flow characteristics. Dissolution rate of raw QUR was found to be less than 10% in 60 min while in case of QUR loaded LSCs, more than 90% drug release was observed within 5 min. Absence of crystalline peaks of QUR in the DSC and PXRD reports of LSCs and their porous appearance in SEM micrographs indicate that QUR was successfully incorporated in the LSCs. The developed formulation was found to be stable on storage under accelerated stability conditions.

Introduction: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation. Area covered: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues. Expert opinion: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.

Skin diseases are the fourth leading non-fatal skin conditions that act as a burden and affect the world economy globally. This condition affects the quality of a patient's life and has a pronounced impact on both their physical and mental state. Treatment of these skin conditions with conventional approaches shows a lack of efficacy, long treatment duration, recurrence of conditions, systemic side effects, etc., due to improper drug delivery. However, these pitfalls can be overcome with the applications of nanomedicine-based approaches that provide efficient site-specific drug delivery at the target site. These nanomedicine-based strategies are evolved as potential treatment opportunities in the form of nanocarriers such as polymeric and lipidic nanocarriers, nanoemulsions along with emerging others viz. carbon nanotubes for dermatological treatment. The current review focuses on challenges faced by the existing conventional treatments along with the topical therapeutic perspective of nanocarriers in treating various skin diseases. A total of 213 articles have been reviewed and the application of different nanocarriers in treating various skin diseases has been explained in detail through case studies of previously published research works. The toxicity related aspects of nanocarriers are also discussed.

Fisetin (FS) is a polyphenolic phytoconstituent reported to have various pharmacological activities such as antioxidant, antiparkinsonian, and antidepressant. An analytical method was developed and validated for the estimation of FS by ultrafast liquid chromatography using C-18 reverse phase column. Acetonitrile and orthophosphoric acid (0.2% v/v) in the ratio of 30:70 v/v was used as mobile phase. Flow rate was set at 1 mL/min. Chromatogram of FS was detected at wavelength of 362 nm. Retention time for FS was found to be 7.06 min. The developed method was found to be linear in the range of 2-10 μg/mL with regression coefficient of 0.9985. The method was validated as per the International Conference on Harmonization (ICH) Q2 (R1) guidelines. The percentage recovery was in the range of 95%-105%, which indicated the accuracy of the method. The percentage relative standard deviation (RSD) was found to be2%, which indicates the precision of the method. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.46 and 1.41 μg/mL, respectively. The developed method was found to be robust as there was no significant change in response with change in flow rate, ratio of mobile phase, and pH. The method was successfully applied for estimation of drug loading and drug release from self-nanoemulsifying drug delivery system (SNEDDS). The % drug loading of FS in prepared liquid SNEDDS formulation was found to be 101.95%. The results of dissolution studies indicated 67.78% FS release in water at the end of 60 min.

Outbreak of Coronavirus disease 2019 (COVID-19) started in mid of December 2019 and spread very rapidly across the globe within a month of its outbreak. Researchers all across the globe started working to find out its possible treatments. However, most of initiatives taken were based on various hypotheses and till date no successful treatments have been achieved. Some strategies adopted by China where existing antiviral therapy was initially used to treat COVID-19 have not given very successful results. Researchers from Thailand explored the use of combination of anti-influenza drugs such as Oseltamivir, Lopinavir and Ritonavir to treat it. In some cases, combination therapy of antiviral drugs with chloroquine showed better action against COVID-19. Some of the clinical studies showed very good effect of chloroquine and hydroxychloroquine against COVID-19, however, they were not recommended due to serious clinical toxicity. In some cases, use of rho kinase inhibitor, fasudil was found very effective.In some of the countries, antibody-based therapies have proved fairly successful. The use of BCG vaccines came in light; however, they were not found successful due to lack of full-proof mechanistic studies. In Israel as well as in other developed countries, pluristems allogeneic placental expanded cell therapy has been found successful. Some phytochemicals and nutraceuticals have also been explored to treat it. In a recent report, the use of dexamethasone was found very effective in patients suffering from COVID-19. Its effect was most striking among patients on ventilator. The research for vaccines that can prevent the diseaseis still going on. In light of the dynamic trends, present review focuses on etiopathogenesis, factors associated with spreading of the virus, and possible strategies to treat this deadly infection. In addition, it attempts to compile the recent updates on development of drugs and vaccines for the dreaded disease., Highlights • Life cycle of SARS-CoV-2 in host cell have been demonstrated. • CT scan and RT-PCR are very helpful in diagnosis of COVID-19 infection. • Antiviral, antimalarial, antimicrobial and ROCK inhibitors were found very effective. • Dietary supplements such as Glucosamine and Vitamin-C were found effective. • Vaccines such as Canine Corona vaccine and BCG have been found promising. • Cell based, Convalescent plasma and Pluristems allogeneic placental expanded cell therapies are being tested.

Aim of the present study was to give a second life to the long-abandoned drug, sulfapyridine (SP) for its anti-arthritic potential by design of nano-vesicular delivery system. For this, intra-articular delivery of its liposomal formulation was tried. As the prepared formulation exhibited rapid drug leakage, an arthritis responsive prodrug of SP showing lability towards synovial enzymes was synthesized to exploit the over-expression of arthritis specific enzymes. Prodrug (SP-PD) exhibited better retention in liposomes as compared to the drug, preventing its escape from synovium. Hydrolysis of SP-PD in human plasma and synovial fluid indicated its high susceptibility to enzymes. The liposomes of SP-PD exhibited larger mean size, less PDI and higher zeta potential as compared to those for SP liposomes. In arthritic rats, prodrug liposomes were found to reverse the symptoms of inflammation, including the levels of biochemical markers. Liposomes of bio-responsive prodrug, therefore, offer a revolutionary approach in the treatment of rheumatoid arthritis.

Solid self-nanoemulsifying drug delivery system (S-SENDDS) containing Curcumin (CRM) were prepared using combination of Ganoderma lucidum extract powder (GLEP) and probiotics (PB) as carriers. Liquid SNEDDS containing CRM were prepared by mixing Capmul MCM, Labrafil M1944CS, Tween 80 and Transcutol P. These were further spray dried and finally converted into spheroids. The droplet size of reconstituted S-SNEDDS powder and spheroids was found in the range of 35 to 37 nm, zeta potential in the range of - 21.48 to -23.22 mV and drug loading in the range of 95-96%. The release of drug from formulations was found to be more than 90%. Similarly, significant improvement (p0.05) in permeability of CRM was observed through SNEDDS using Caco2 cell lines. The non-significant difference (p0.05) in drug loading, droplet size, dissolution rate and angle of repose between L-SNEDDS and S-SNEDDS indicated the potential of GLEP-PB to produce stable SNEDDS.

An infectious disease of the colon, recurrent Clostridium difficile infection (RCDI), is hitherto considered insurmountable leading to significant morbidity and mortality. Gut dysbiosis, generally resulting from frequent use of antibiotics, is considered to be responsible for the etiopathogenesis of RCDI. Ironically, the conventional treatment strategies for the disease also include the use of anti- infective drugs such as metronidazole, vancomycin and fidaxomycin. As a result of the efforts to overcome the limitations of these treatment options to control the recurrence of disease, faecal microbiota transplant (FMT) has emerged as an effective and safe alternative. It is pertinent to add here that FMT is defined as the process of engraftment of fecal suspension from the healthy person into the gastrointestinal tract of the diseased individual aiming at the restoration of gut microbiota. FMT has proved to be quite successful in the treatment of recurrent and resistant Clostridium difficile infections. In the last three decades, a lot of information has been generated on the use of FMT for RCDI. A number of clinical trials have been reported with generally very high success rates. However, a very small number of patents could be found in the area, indicating that there still exists lacuna in the knowledge about FMT with respect to its preparation, regulation, mode of delivery and safety. The current review attempts to dive deeper to discuss the patents available in the area while supporting the information contained therein with the non-patent literature.

The objective of the current investigation was to develop a simple, rapid, and stability-indicating high-performance liquid chromatography method and to study the degradation behavior of sulfapyridine (SP) under different International Conference on Harmonization (ICH)-recommended conditions. The chromatographic method was developed using C

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation which ultimately leads to severe disability and premature mortality. It has a global prevalence of around 1% with the incidence among women being 2–3 times more than in men. The pathogenesis of the disease involves preclinical RA, genetic factors, and environmental factors. The RA has no known cure and the primary aim of treatment remains to attain lowest possible disease activity and recovery if possible. The present review highlights the literature on the different treatment options available for the treatment of RA, their mechanisms of action, side effects, and novel drug delivery systems that are in use for drug administration with the main focus on novel drug delivery systems of non-steroidal anti-inflammatory drugs. Different classes of drugs such as corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs), and biologics are discussed with examples of most widely used drugs among each class. Conventional drug therapy has many disadvantages like low solubility and permeability, poor bioavailability, degradation by gastrointestinal enzymes, first pass metabolism, food interactions, and toxicity. Novel drug delivery systems like microspheres, nanoparticles, dendrimers, liposomes, and so on are promising tools as they have been successful in overcoming the disadvantages associated with conventional drug delivery system. The present review squares the various novel drug delivery systems that have been explored for administering anti-rheumatic drugs and the advantages associated with these novel drug delivery systems in comparison to conventional drug delivery systems.

Ethnopharmacological relevance Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant. Aim of the study Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta. Materials and methods Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied. Results Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner. Conclusions The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

© 2019 Elsevier B.V. The growing disease burden of diabetes mellitus is an important public health concern, affecting over 400 million people globally. This epidemic, if not controlled in time, leads to life threatening complications, compromise in quality of life, and eventually mortality. Over time, many attempts have been made for the effective treatment of diabetes but true success has never been achieved. Pharmacological and non-pharmacological approaches for the treatment of hyperglycaemia have been ever-evolving due to limitations of current therapies. Non pharmacological management which includes diet management and exercise, has been the primary focus for self-management of diabetes. The pharmacological management includes oral antihyperglycaemics, phytoconstituents, and combination products. Advancements such as nanocarrier delivery systems have been made in drug delivery to overcome the challenges such as poor bioavailability associated with conventional dosage forms currently employed in diabetes treatment. In recent years, much emphasis has been given to synbiotics that act on gut microbiota, as an emerging therapy for diabetes. The current review discusses different treatment strategies for diabetes management starting from insulin therapy to synbiotics. The combination of herbal phytoconstituents with synthetic drugs, synthetic drug combinations, novel drug delivery systems for insulin are highlighted. Moreover, the role of gut dysbiosis in diabetes and its treatment by administration of synbiotics in various clinical as well as non clinical studies has been discussed in detail.

Lipid-based nanovesicles such as liposomes, niosomes, and ethosomes are now well recognized as potential candidates for drug delivery and theranostic applications. Some of them have already stepped forward from laboratory to market. The property to entrap lipophilic drugs in their bilayers and hydrophilic drugs in the aqueous milieu makes them a unique carrier for drug delivery. Delivery of drugs/diagnostics to various organs/tissues/cells via nanovesicles is considered to be a topic of long-standing interest with new challenges being posed to formulation scientists with new developments. The key challenge in this context is the physiological and pathological conditions, which make the delivery of drugs extremely difficult at the disease locus and makes their precise delivery ineffective. This chapter gives an insight into the role of novel nanovesicles in the field of drug delivery. We present an overview of the formulation and characterization and role of diverse nanovesicles. A comprehensive update about their application and current as well as potential challenges have also been discussed.

Though vesicular delivery systems have been widely explored and reviewed, no comprehensive review exists that covers their development from the inception of the concept to its culmination in the form of regulated marketed formulations. With the advancement of scientific research in the field of nanomedicine, certain category of vesicular delivery systems have successfully reached the global market. Despite extensive research and highly encouraging results in a plethora of pathological conditions in the preclinical studies, translation of these nanomedicines from laboratory to market has been very limited. Aim of this review is to describe comprehensively the various colloidal delivery systems, focusing mainly on their conventional and advanced methods of preparation, different characterization techniques and main success stories of their journey from bench to bedside of the patient. The review also touches the finer nuances of the use of modern formulation approach of DoE (Design of Experiments) in their formulation and the status of regulatory guidelines for the approval of these nanomedicines.

The aim of present study was to co-administer curcumin (CRM) liquisolid pellets and coated duloxetine hydrochloride (DXH) pellets in rats to treat neuropathic pain (NP) associated with chronic constriction injury (CCI). To formulate liquisolid pellets of CRM, it was first dissolved in Tween-80 and then adsorbed on the porous surface of MCC PH102 and Syloid XDP that were used as carrier and coating materials, respectively. Central composite design was used to optimize the liquisolid formulation. The results of powder X-ray diffraction studies, differential scanning calorimetry, and scanning electron microscopy showed complete solubility of drug in Tween-80 followed by its complete adsorption on the porous surface of Syloid XDP and MCC PH102. Both DXH and liquisolid CRM powders were converted into pellets using extrusion-spheronization. DXH pellets were further coated with Eudragit S100 to bypass the gastric pH. About 32.31-fold increase in dissolution rate of CRM present in liquisolid formulation was observed as compared to its unprocessed form. Similarly, the dissolution profile in 0.1 N HCl for Eudragit S100-coated DXH showed complete protection of drug for 2 h and complete release after its introduction in buffer medium (0.2 M phosphate buffer pH 6.8). he pharmacokinetic studies carried out on rats revealed 7.3-fold increase in bioavailability of CRM present in liquisolid pellets and 4.1-fold increase in bioavailability of DXH present in coated pellets was observed as compared to their unprocessed pellets. This increase in bioavailability of drugs caused significant amelioration of CCI-induced pain in rats as compared to their unprocessed forms. The histological sections showed better improvement in regeneration of nerve fibers in rats.

© 2020 Elsevier B.V. Simvastatin (SIM) and glimepiride (GLM) were co-formulated into nanosuspensions and self-nanoemulsifying drug delivery systems (SNEDDS) to improve their dissolution rate and oral bioavailability. Nanosuspension was prepared by liquid anti-solvent precipitation method, involving supersaturation of a solution by mixing the drug solution in an antisolvent. Liquid SNEDDS were prepared by loading drugs into an isotropic mixture of Capmul MCM, Labrafil M1944CS, Tween-80 and Transcutol P. Both formulations were solidified using spray drying. Enhancement in dissolution rate by 6.4 folds and 4.45 folds was observed for GLM and SIM respectively by preparing their nano-formulations. Drugs’ permeability was also enhanced by loading them into nano-formulations. The pharmacokinetic studies were conducted on rats which revealed increase in oral bioavailability by 6.69- and 4.22-folds for GLM and 1.76- and 2.68-folds for SIM respectively for nanosuspension and solid SNEDDS than their unprocessed forms. Both dissolution rate and oral bioavailability of SIM and GLM got significantly improved through S-SNEDDS and nanosuspension. However, performance of nanosuspension was found better than SNEDDS in terms of dissolution rate and oral bioavailability.