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Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future., (© 2023. Fondazione Società Italiana di Neurologia.)

Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article provides a summary of established interactions between the gut microbiome and ND. Post-biotic is believed to mediate its neuroprotection by elevating the level of dopamine and reducing the level of α-synuclein in substantia nigra, protecting the loss of dopaminergic neurons, reducing the aggregation of NFT, reducing the deposition of amyloid β peptide plagues and ameliorating motor deficits. Moreover, mediates its neuroprotective activity by inhibiting the inflammatory response (decreasing the expression of TNFα, iNOS expression, free radical formation, overexpression of HIF-1α), apoptosis (i.e. active caspase-3, TNF-α, maintains the level of Bax/Bcl-2 ratio) and promoting BDNF secretion. It is also reported to have good antioxidant activity. This review offers an overview of the latest findings from both preclinical and clinical trials concerning the use of post-biotics in ND., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The study was performed to evaluate the neuroprotective effects of Benfotiamine (BFT) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in rats. The rats were given daily doses of BFT (100 mg/kg, 200 mg/kg) through oral administration for 42 days. The rats were given a single bilateral dosage of MPTP (0.1 mg/nostril) intranasally once before the drug treatment to induce PD. On day 42, the animals were subjected to various behavioral paradigms. Post-treatment with BFT for 42 days significantly improved the motor and nonmotor fluctuations of MPTP. The results demonstrated that treatment with BFT ameliorated MPTP-induced disorders in behavior, body balance, and dopamine levels in the mid-brain. Among the post-treated groups, a high dose of BFT was the most effective treatment. Mean values are indicated in ±SEM, n = 5***(p < 0.001) when compared with the vehicle control, n = 5 ### (p < 0.001) when compared with the disease control; (p < 0.001) when compared with the BFT per se; (p < 0.001) when compared with the low dose of BFT; (p < 0.001) when compared with the high dose of BFT. Our finding suggests that BFT contributed to superior antioxidant, and anti-inflammatory and could be a novel therapeutic method for PD management. In conclusion, BFT could be a potential drug candidate for curbing and preventing PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer is a diverse disease caused by transcriptional changes involving genetic and epigenetic features that influence a huge variety of genes and proteins. Skin cancer is a potentially fatal disease that affects equally men and women globally and is characterized by many molecular changes. Despite the availability of various improved approaches for detecting and treating skin cancer, it continues to be the leading cause of death throughout society. This review highlights a general overview of skin cancer, with an emphasis on epidemiology, types, risk factors, pathological and targeted facets, biomarkers and molecular markers, immunotherapy, and clinical updates of investigational drugs associated with skin cancer. The skin cancer challenges are acknowledged throughout this study, and the potential application of novel biomarkers of skin cancer formation, progression, metastasis, and prognosis is explored. Although the mechanism of skin carcinogenesis is currently poorly understood, multiple articles have shown that genetic and molecular changes are involved. Furthermore, several skin cancer risk factors are now recognized, allowing for efficient skin cancer prevention. There have been considerable improvements in the field of targeted treatment, and future research into additional targets will expand patients' therapeutic choices. In comparison to earlier articles on the same issue, this review focused on molecular and genetic factors and examined various skin cancer-related factors in depth., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Amongst different routes of drug delivery systems, ophthalmic drug delivery still requires a careful investigation and strict parameter measurements because the eyes are one of the most sensitive parts of the body and require special attention. The conventional systems for eyes lead to rapid elimination of formulation and hence very small contact time on the ocular epithelium. The current review article covers various types of polymers used in ocular drug delivery along with their applications/ limitations. Polymers are widely used by researchers in prodrug techniques and as a penetration enhancer in ocular delivery. This article covers the role and use of different polymeric systems which makes the final formulation a promising candidate for ophthalmic drug delivery. The researchers are still facing multiple challenges in order to maintain the therapeutic concentration of the drug in the eyes because of its complex structure. There are several barriers that further restrict the intraocular entry of the drug. In order to remove/reduce such challenges, these days various types of polymers are used for ocular delivery in order to develop different drug carrier systems for better efficacy and stability. The polymers used are highly helpful in increasing residence time by increasing the viscosity at the ocular epithelium layer. Such preparations also get easily permeated in ocular cells. The combination of different polymeric properties makes the final formulation stable with prolonged retention, high viscosity, high permeability, and better bioavailability, making the final formulation a promising candidate for ocular drug delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder brought on by mutations in the DMD gene, which prevent muscle cells from expressing the dystrophin protein. CRISPR/Cas9 technology has evolved as potential option to treat DMD due to its ability to permanently skip exons, restoring the disrupted DMD reading frame and leading to dystrophin restoration. Even though, having potential to treat DMD, the delivery, safety and efficacy of this technology is still challenging. Several delivery methods, including viral vectors, nanoparticles, and electroporation, have been explored to deliver CRISPR/Cas9 to the targeted cells. Despite the potential of CRISPR/Cas9 technology in the treatment of DMD, several limitations need to be addressed. The off-target effects of CRISPR/Cas9 are a major concern that needs to be addressed to avoid unintended mutations. The delivery of CRISPR/Cas9 to the target cells and the immune response due to the viral vectors used for delivery are a few other limitations. The clinical trials of CRISPR/Cas9 for DMD provide valuable insights into the safety and efficacy of this technology in humans and the limitations that need to be known. Therefore, in this review we insightfully discussed the challenges and limitations of CRISPR/Cas9 in the treatment of DMD and delivery strategies used, and the ongoing efforts to overcome these challenges and restore dystrophin expression in DMD patients in the ongoing trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Advances in technology and increased accessibility to modern gadgets have opened up new options for giving alternate recreational activities. The country has seen rapid growth in the smartphone market over the past decade, and mobile phones are preferred by the vast majority of gamers over traditional personal computers and laptops. The coronavirus disease 2019 (COVID-19) pandemic and related restrictions, online teaching, and the use of the internet for work have forced people to resort to the internet more than during the pre-pandemic period. There have not been many studies done to evaluate internet addiction (IA) and internet gaming disorder (IGD) among young people in India, and research is needed to quantify the magnitude of the problem and undertake timely public health actions., Methods: A cross-sectional study was conducted among 400 young people aged 10 to 24 years in Kolar district. Young people meeting the eligibility criteria from schools and colleges were randomly selected to include 67 participants per taluk. Standardized validated nine-item Internet Gaming Disorder Scale-Short-Formand 20-item Internet Addiction Test questionnaire were used to collect data. Data were entered using EpiData version 3.1 (EpiData Association, Odense, Denmark) and analyzed using IBM SPSS version 20 (IBM Corp., Armonk, NY). A p-value < 0.05 was considered statistically significant., Results and Conclusion: COVID-19 control measures have caused more young people to access the internet in the recent past. Among young people studied, 58.5% and 6.5% have IA and IGD, respectively. Factors like living in urban areas, belonging to families above the poverty line, not living with parents, years of internet use, and increased access to internet/gadgets during the COVID-19 pandemic were significantly associated with IA and IGD. Since addiction to the internet and online gaming is known to have a negative impact on the mental health and well-being of young people, in light of IGD being listed in the International Classification of Diseases, there is an urgent need to target these conditions, especially for young people., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mokshathaa et al.)

Introduction: Mental health is defined as "a state of well-being in which the person realizes his or her own skills, can deal with the normal stresses of life, can work effectively and fruitfully, and is able to make a contribution to his or her community." Although mental health is essential to human survival, it is often given less attention than physical health in many parts of the world., Objectives: The aim of this study is to evaluate the rural community's awareness regarding mental health issues and the factors that contribute to them., Materials and Methods: A cross-sectional study was undertaken in the rural community; 350 study subjects were selected from the village of Devarayasamudra by using convenient sampling, 350 households were selected, and household-level interviews were done using the Mental Health Knowledge Schedule questionnaire. Participants aged more than 18 were included in the study, and locked households, even after two visits, were excluded from the study., Results: The median aggregate knowledge score was 31 (SD = 7.1), with the minimum and maximum values being 11 and 44 out of 45 knowledge items, respectively. The total knowledge score found that 178 (50.8%) respondents had insufficient mental health knowledge based on the percentage of the study population with a cut-off score below and above the median score. A multivariate logistic regression analysis confirmed that participants who were illiterate had 1.76 (1.15-2.26) times the chances of having insufficient knowledge compared to professionals, and this remained true even after adjusting for other variables as well., Conclusion: The present study concluded that more than 50% (50.8%) of the participants had inadequate awareness of mental health and mental illness. This highlights the need to spread awareness about mental health education among the general community., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Jayan et al.)

Polycystic Ovarian Syndrome (PCOS) comprises a set of symptoms that pose significant risk factors for various diseases, including type 2 diabetes, cardiovascular disease, and cancer. Effective and safe methods to treat all the pathological symptoms of PCOS are not available. The gut microbiota has been shown to play an essential role in PCOS incidence and progression. Many dietary plants, prebiotics, and probiotics have been reported to ameliorate PCOS. Gut microbiota shows its effects in PCOS via a number of mechanistic pathways including maintenance of homeostasis, regulation of lipid and blood glucose levels. The effect of gut microbiota on PCOS has been widely reported in animal models but there are only a few reports of human studies. Increasing the diversity of gut microbiota, and up-regulating PCOS ameliorating gut microbiota are some of the ways through which prebiotics, probiotics, and polyphenols work. We present a comprehensive review on polyphenols from natural origin, probiotics, and fecal microbiota therapy that may be used to treat PCOS by modifying the gut microbiota.

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Curcumin (CRM) is known to possess various therapeutic properties, such as anti-inflammatory and antidiabetic properties, and is, therefore, considered to be an effective therapeutic., Objective: A sensitive method for the estimation of CRM in plasma, as well as fecal matter-based solid self-nano emulsifying drug delivery system (S-SNEDDS), has been reported for the first time., Methods: A bioanalytical method was optimized using Box-Behnken Design having 13 runs and 3 responses. The optimized method was developed using methanol and water (70:30 v/v) with a flow rate of 1 mL/min. Quercetin was used as an internal standard. A specificity test was also performed for the developed CRM solid self-nano emulsifying drug delivery system., Results: The retention time of CRM was found to be 14.18 minutes. The developed method was validated and found to be linear in the range of 50-250 ng/mL with an R 2 of 0.999. Accuracy studies indicated that CRM had a percentage recovery of less than 105% and more than 95%, respectively. Precision studies were carried out for inter, intraday, and inter-analyst precision, and the %RSD was found to be less than 2%. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.37 ng/mL and 10.23 ng/mL, respectively. Stability studies for shortterm, long term and freeze-thaw cycles showed a %RSD of less than 2%, indicating the stability of CRM in the plasma matrix. Moreover, the blank fecal microbiota extract slurry did not show any peak at the retention time of CRM in a CRM-loaded solid nanoemulsifying drug delivery system containing fecal microbiota extract indicating its specificity., Conclusion: Hence, the developed method can have clinical implications as it helps estimate CRM in blood samples and also provides a simple and sensitive method for the estimation of plant-based flavonoids along with fecal microbiota extract formulations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe's worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.

Polysaccharides (PS) represent a broad class of polymer-based compounds that have been extensively researched as therapeutics and excipients for drug delivery. As pharmaceutical carriers, PS have mostly found their use as adsorbents, suspending agents, as well as cross-linking agents for various formulations such as liposomes, nanoparticles, nanoemulsions, nano lipid carriers, microspheres etc. This is due to inherent properties of PS such as porosity, steric stability and swellability, insolubility in pH. There have been emerging reports on the use of PS as therapeutic agent due to its anti-inflammatory and anti-oxidative properties for various diseases. In particular, for Crohn's disease, ulcerative colitis and inflammatory bowel disease. However, determining the dosage, treatment duration and effective technology transfer of these therapeutic moieties have not occurred. This is due to the fact that PS are still at a nascent stage of development to a full proof therapy for a particular disease. Recently, a combination of polysaccharide which act as a prebiotic and a probiotic have been used as a combination to treat various intestinal and colorectal (CRC) related diseases. This has proven to be beneficial, has shown good in vivo correlation and is well reported. The present review entails a detailed description on the role of PS used as a therapeutic agent and as a formulation pertaining to gastrointestinal diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Synbiotics, are a combination of probiotics and prebiotics. They play an important role in metabolizing different nutritional substrates and thus helps in the maintenance of human health. Any disbalance in the gut microflora, known as dysbiosis, is known to lead to a number of diseased conditions. It can be reverted by the administration of synbiotics. Present review highlights various mechanistic pathways through which synbiotics act as therapeutics. The dual role of synbiotics as nutraceutical and excipient in developing oral formulations are entailed with case studies. The findings entailed that there exist numerous studies on prebiotics as well as probiotics have been carried out to show their effects in several diseases. However, the concept of combining together them for prevention and treatment of various pathological conditions accruing from dysbiosis is relatively new. Synbiotics, however, face challenge of low stability during their sojourn in the GIT, which is generally overcome by various encapsulation techniques. Various studies also showed potential role of synbiotics in drug delivery. However, it is an emerging area and lacks clinical correlation. It is important to focus on clinical trials of formulations wherein synbiotics have been used as therapeutic moiety as well as pharmaceutical carrier for treating various diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access. Therefore, current research is focused on developing newer advanced formulations from potential drug candidates including nutraceuticals with desirable properties viz, affordability, ease of availability, ease of administration, stability under room temperature, and potentially longer shelf-lives. As such, various nutraceutical-based products such as compounds could be promising agents for effectively managing COVID-19 symptoms and complications. Most importantly, regular consumption of such nutraceuticals has been shown to boost the immune system and prevent viral infections. Nutraceuticals such as vitamins, amino acids, flavonoids like curcumin, and probiotics have been studied for their role in the prevention of COVID-19 symptoms such as fever, pain, malaise, and dry cough. In this review, we have critically reviewed the potential of various nutraceutical-based therapeutics for the management of COVID-19. We searched the information relevant to our topic from search engines such as PubMed and Scopus using COVID-19, nutraceuticals, probiotics, and vitamins as a keyword. Any scientific literature published in a language other than English was excluded. PRACTICAL APPLICATIONS: Nutraceuticals possess both nutritional values and medicinal properties. They can aid in the prevention and treatment of diseases, as well as promote physical health and the immune system, normalizing body functions, and improving longevity. Recently, nutraceuticals such as probiotics, vitamins, polyunsaturated fatty acids, trace minerals, and medicinal plants have attracted considerable attention and are widely regarded as potential alternatives to current therapeutic options for the effective management of various diseases, including COVID-19., (© 2022 The Authors. Journal of Food Biochemistry published by Wiley Periodicals LLC.)

Diabetic foot ulcer (DFU) is a multifactorial disease and one of the complications of diabetes. The global burden of DFU in the health sector is increasing at a tremendous rate due to its cost management related to hospitalization, medical costs and foot amputation. Hence, to manage DFU/DWs, various attempts have been made, including treating wounds systematically/topically using synthetic drugs, herbal drugs, or tissue engineering based surgical dressings. However, less attention has been paid to the intrinsic factors that are also the leading cause of diabetes mellitus (DM) and its complications. One such factor is gut dysbiosis, which is one of the major causes of enhancing the counts of Gram-negative bacteria. These bacteria produce lipopolysaccharides, which are a major contributing factor toward insulin resistance and inflammation due to the generation of oxidative stress and immunopathy. These all lead to DM and DFU. Probiotics are the commercial form of beneficial gut microbes that are taken as nutraceuticals by people of all ages to improve gut immunity and prevent gut dysbiosis. However, the role of probiotics has been less explored in the management of DFU. Hence, the therapeutic potential of probiotics in managing DFU is fully described in the current review. This report covers the linkage between gut dysbiosis and DFU, sources of probiotics, the mechanisms of probiotics in DW healing, and the impact of probiotic supplementation in treating DFU. In addition, techniques for the stabilization of probiotics, market status, and patents related to probiotics have been also covered. The relevant data were gathered from PubMed, Scopus, Taylor and Francis, Science Direct, and Google Scholar. Our systematic review discusses the utilization of probiotic supplementation as a nutraceutical for the management of DFU.

Rosmarinic acid (RA) is a polyphenolic metabolite found in various culinary, dietary sources, and medicinal plants like Coleus scutellarioides (Linn) Benth., Lavandula angustifolia Linn., Mellisa officinalis Linn., Origanum vulgare Linn., Rosmarinus officinalis Linn., Zataria multiflora Boiss. and Zhumeria majdae Rech. F. Apart from its dietary and therapeutic values, RA is an important anticancer phytochemical owing to its multi-targeting anticancer mechanism. These properties provide a scope for RA's therapeutic uses beyond its traditional use as a dietary source. However, its oral bioavailability is limited due to its poor solubility and permeability. This impedes its efficacy in treating cancer. Indeed, in recent years, tremendous efforts have been put towards the development of nanoformulations of RA for treating cancer. However, this research is in its initial stage as bringing a nanoparticle into the market itself is associated with many issues such as stability, toxicity, and scale-up issues. Considering these pitfalls during formulation development and overcoming them would surely provide a new face to RA as a nanomedicine to treat cancer. A literature search was conducted to systematically review the various biological sources, extraction techniques, and anticancer mechanisms through which RA showed multiple therapeutic effects. Various nanocarriers of RA pertaining to its anticancer activity are also discussed in this review.

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, -26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.

Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of -19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH.

Purpose: The aim of current study is to formulate, optimize and characterize the developed formulation of Mesalamine-Curcumin Nanostructured Lipid Carriers (Mes-Cur NLCs)., Methods: It was formulated using high pressure homogenization followed by probe sonication and formulation variables were optimized using Central Composite Design. The particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug release, cytotoxicity on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells and efficacy on RAW264.7 cells for optimized formulation was determined., Results: The PS, ZP and EE were found to be 85.26 nm, -23.7 ± 7.45 mV, 99.2 ± 2.62 % (Mes) and 84 ± 1.51 % (Cur), respectively. The good correlation between predicted and obtained value indicated suitability and reproducibility of experimental design. NLCs showed spherical shape as confirmed by TEM. In vitro drug release profile of prepared formulation showed that Mes exhibited 100 % release at 48 h, whereas Cur exhibited 82.23 ± 2.97% release at 120 h. Both the drugs exhibited sustained release upon incorporation into the NLCs. The absence of any significant cell death during MTT assay performed on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells indicated that NLCs' were safe for use. Furthermore, significant reduction in nitric oxide level during anti-inflammatory evaluation of formulation on RAW264.7 cells showed excellent potential for the formulation to treat inflammation. The formulation was found stable as no significant difference between the PS, ZP and EE of the fresh and aged NLCs was observed., Conclusion: The outcomes of study deciphered successful formulation of Mes-Cur NLCs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Advances in biotechnology have led to improving human health with number of novel approaches to mitigate life-threatening diseases such as human immunodeficiency virus (HIV) infection, cancer, and neurodegenerative diseases. In the case of HIV, the damage caused by the retrovirus to the immune system leads to opportunistic infection as well as an elevated risk of autoimmune disease and cancer. Furthermore, clinical symptoms associated with the virus itself may arise. Antiretroviral drug therapy using reverse transcriptase inhibitors, protease inhibitors, fusion inhibitor, chemokine receptor 5 antagonist and integrase strand transfer inhibitors have shown promising results in treating HIV infection and available in market in the form of various dosage forms. However, they are unable to completely cure the disease because of complexity in pathogenesis of HIV. In addition, these drugs have some limitations of poor solubility, permeability or, poor receptor binding capacity. To overcome these drawbacks, many novel drug delivery systems for the drugs belonging to above mentioned categories have been developed. The possibility of treating HIV infection using CRISPR-Cas9 gene editing has been found in 2015. This provided a new area of research to the scientists who are working towards alternative treatment strategies for HIV infections. The present article describes about various treatment strategies used to treat HIV infections with special emphasis on the role of CRISPR/Cas9 gene-based technology. The potential benefits of specific epigenetic modification in the c-c chemokine receptor 5 gene (CCR5) via various delivery methods are also highlighted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma., (© 2022. The Author(s).)

Non-aqueous nanoemulsion (NANE) of Alpinia galanga extract (AGE) was prepared using Palmester 3595 (MCT oil) as oil phase, Cremophor RH 40-Transcutol P® as surfactant-co-surfactant (S mix ), and glycerin as non-aqueous polar continuous phase. The composition was optimized by applying three-level, four factor Box-Behnken design (BBD). The mean droplet size and zeta potential of the optimized AGE NANE was found to be 60.81 ± 18.88 nm and -7.99 ± 4.14 mV, respectively. The ex vivo permeation studies of AGE NANE and AGE per se on porcine skin reported flux of 125.58 ± 8.36 µg/cm 2 h -1 and 12.02 ± 1.64 µg/cm 2  h -1 , respectively. Therefore, the enhancement ratio has shown 10-folds increase in the flux for AGE NANE when compared to extract per se. Later, confocal laser scanning microcopy confirmed that AGE NANE were able to penetrate into skin's stratum by trans-follicular transport mechanism. The stability studies of AGE NANE confirmed its stability at 30 ± 2 °C/75 ± 5 % RH and 5 ± 3 °C. The efficacy of AGE NANE was evaluated in vivo on imiquimod (IMQ) induced mouse model. The mice treated with low and high doses of AGE NANE (groups VI and VII) showed significant (p < 0.05) amelioration of psoriasis. Results of histopathology indicated reduction in psoriasis area severity index in AGE NANE treated mice (group VI and group VII)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Diabetic wound (DW) is a secondary application of uncontrolled diabetes and affects about 42.2% of diabetics. If the disease is left untreated/uncontrolled, then it may further lead to amputation of organs. In recent years, huge research has been done in the area of wound dressing to have a better maintenance of DW. These include gauze, films, foams or, hydrocolloid-based dressings as well as polysaccharide- and polymer-based dressings. In recent years, scaffolds have played major role as biomaterial for wound dressing due to its tissue regeneration properties as well as fluid absorption capacity. These are three-dimensional polymeric structures formed from polymers that help in tissue rejuvenation. These offer a large surface area to volume ratio to allow cell adhesion and exudate absorbing capacity and antibacterial properties. They also offer a better retention as well as sustained release of drugs that are directly impregnated to the scaffolds or the ones that are loaded in nanocarriers that are impregnated onto scaffolds. The present review comprehensively describes the pathogenesis of DW, various dressings that are used so far for DW, the limitation of currently used wound dressings, role of scaffolds in topical delivery of drugs, materials used for scaffold fabrication, and application of various polymer-based scaffolds for treating DW., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ankit Awasthi et al.)

Fisetin is a polyphenolic flavonoid reported to have antioxidant, anti-inflammatory, and anti-cancer activities. However, it loses its importance as an effective phytochemical due to its poor water solubility and lower bioavailability. In the present study, the self-nanoemulsifying drug delivery system (SNEDDS) of fisetin was developed in order to improve its pharmacological activity. The developed SNEDDS of fisetin was evaluated for improving the rotenone-induced behavioral changes in the rats, and its efficacy was compared with naïve fisetin. It was noticed that fisetin loaded in the SNEDDS formulation significantly (p < 0.001) ameliorated the rotenone-induced alteration in the body weight, grip strength, beam walk, postural instability, etc., in rats when compared to the effect of naïve fisetin. Naïve fisetin significantly (p < 0.05) ameliorated the effect of rotenone on the level of dopamine only at a higher dose. Whereas, SNEDDS of fisetin produced a significant (p < 0.05) effect at both dose levels when compared with the diseased group as well as also produced a significant (p < 0.05) effect when compared with the naïve fisetin group. The results of histopathological examination revealed about the neuroprotective effect of SNEDDS loaded with fisetin as observed through the protection of neuronal damage. From this study, it was concluded that SNEDDS improved the anti-Parkinsonian activity of fisetin by improving the behavioral alteration produced by rotenone due to enhancement in its solubility and bioavailability., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Type 2 diabetes mellitus is one of the most common and life-threatening diseases found across the globe. It occurs due to insulin resistance (IR). Major causes of IR include obesity, sedentary life style and hyperlipidemia. Glimepiride (GLM) is one of the most common oral sulphonyl ureas that is being used to treat diabetes and Simvastatin (SIM) is one of the most common statins that is used to treat hyperlipidaemia. However, both the drugs suffer from dissolution rate limited oral bioavailability. Hence, the aim of present study was to develop two different nanoformulations viz. nanosuspension and self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their potential in treating type 2 diabetes mellitus on streptozotocin (STZ) induced rats. In the present study two such drugs, GLM and SIM were co-formulated into nanosuspension (NS) as well as self-nanoemulsifying drug delivery systems (L-SNEDDS). Both formulations were spray dried for solidification and evaluated for their antidiabetic potential against high fat diet and streptozotocin induced rat model. The study showed significant (p < 0.05) decrease in lipid/cholesterol and blood glucose levels and significant increase in antioxidant levels in the rats treated with NS and SNEDDS containing the drugs alone as well as their combination as compared to their unprocessed forms. However, the efficacy was more prominent in case of combination possibly due to dual benefits i.e., decrease in IR due to statin and control of blood glucose level. Among NS and SNEDDS, NS was found more efficacious than that of the SNEDDS possibly due to higher enhancement of oral bioavailability in case of NS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ethanopharmacological Importance: Alpinia galanga (L.) Willd (AG), belonging to Zingiberaceae family is used as a spice and condiment in various culinary preparations of Indonesia, Thailand and Malaysia. It has been also used as a key ingredient in various traditional systems of medicine for the treatment of throat infection, asthma, urinary ailments, inflammation and rheumatism amongst other conditions. AG is widely used as a functional food and included in various preparations to obtain its nutraceutical and pharmacological benefits of its phytoconstituents such as phenyl propanoids, flavonoids and terpenoids. Over the past decades, several researchers have carried out systematic investigation on various parts of AG. Numerous studies on AG rhizomes have shown positive pharmacological effects such as anti-inflammatory, anticancer, antipsoriasis, antiallergic, neuroprotective and thermogenesis. Till date, no comprehensive review summarizing the exploitation of AG into nanomedicine has been published., Aim of the Review: This comprehensive review aims to briefly discuss cultivation methods, propagation techniques, extraction processes for AG. The ethnopharmacological uses and pharmacological activities of AG extracts and its isolates are discussed in detail which may contribute well in further development of novel drug delivery system (NDDS) i.e. future nanomedicine., Materials and Methods: Information about AG was collected using search engine tools such as Google, Google Scholar, PubMed, Google Patent, Web of Science and bibliographic databases of previously published peer-reviewed review articles and research works were explored. The obtained data sets were sequentially arranged for better understanding of AG's potential., Results: More advanced genetic engineering techniques have been utilized in cultivation and propagation of AG for obtaining better yield. Extraction, isolation and characterization techniques have reported numerous phytoconstituents which are chemically phenolic compounds (phenyl propanoids, flavonoids, chalcones, lignans) and terpenes. Ethnopharmacological uses and pharmacological activity of AG are explored in numerous ailments, their mechanism of action and its further potential to explore into novel drug delivery system are also highlighted., Conclusions: The review highlights the importance of plant tissue culture in increasing the production of AG plantlets and rhizomes. It was understood from the review that AG and its phytoconstituents possess numerous pharmacological activities and have been explored for the treatment of cancer, microbial infection, gastrointestinal disorders, neuroprotective effects, obesity and skin disorders. However, the use of AG as alternative medicine is limited owing to poor solubility of its bioactive components and their instability. To overcome these challenges, novel drug delivery systems (NDDS) have been utilized and found good success in overcoming its aforementioned challenges. Furthermore, efforts are required towards development of scalable, non-toxic and stable NDDS of AG and/or its bioactives., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The current advancements in nanotechnology are as an outcome of the development of engineered nanoparticles. Various metallic nanoparticles have been extensively explored for various biomedical applications. They attract lot of attention in biomedical field due to their significant inert nature, and nanoscale structures, with size similar to many biological molecules. Their intrinsic characteristics which include electronic, optical, physicochemical and, surface plasmon resonance, that can be changed by altering certain particle characteristics such as size, shape, environment, aspect ratio, ease of synthesis and functionalization properties have led to numerous applications in various fields of biomedicine. These include targeted drug delivery, sensing, photothermal and photodynamic therapy, imaging, as well as the modulation of two or three applications. The current article also discusses about the various properties of metallic nanoparticles and their applications in cancer imaging and therapeutics. The associated bottlenecks related to their clinical translation are also discussed., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pulmonary diseases such as lung cancer, asthma and tuberculosis have remained one of the common challenges globally. Polymeric micelles (PMs) have emerged as an effective technique for achieving targeted drug delivery for a local as well as a systemic effect. These PMs encapsulate and protect hydrophobic drugs, increase pulmonary targeting, decrease side effects and enhance drug efficacy through the inhalation route. In the current review, emphasis has been placed on the different barriers encountered by the drugs given via the pulmonary route and the mechanism of PMs in achieving drug targeting. The applications of PMs in different pulmonary diseases have also been discussed in detail.

Fisetin (FS) is a bioactive flavonoid obtained mostly from apple and strawberry and classified under the category of food supplements due to numerous pharmacological effects against various diseases through multiple mechanistic pathways. It acts as excellent neuroprotective, cardioprotective, anti-invasive, anti-tumorigenic, anti-angiogenic, anticancer, antidiabetics, antioxidant, anti-inflammatory agent. Despite having excellent safety and efficacy profile, FS is very less explored to clinical research either as food supplement or, as therapeutic agent due to its poor aqueous solubility, low bioavailability and reduced blood brain barrier permeability. Multiple mechanistic pathways through which FS elicits its pharmacological actions and the challenges associated with FS that compromises therapeutic efficacy are described in this article. The nanoformulations developed to enhance the bioavailability and therapeutic efficacy of FS are also covered with detailed description of research works carried by various researchers. These include nanoemulsions, liposomes, ethosomes, glycerosomes, polymeric micelles, self-nanoemulsifying drug delivery system and polymeric nanoparticles. Various patents pertaining to extraction/isolation, formula composition and therapeutic uses of FS as well as some clinical studies conducted using FS as active moiety are also enlisted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Liquid self-nanoemulsifying drug delivery system (L-SNEDDS) of curcumin and quercetin were prepared by dissolving them in isotropic mixture of Labrafil M1944CS®, Capmul MCM®, Tween-80® and Transcutol P®. The prepared L-SNEDDS were solidified using Ganoderma lucidum extract, probiotics and Aerosil-200® using spray drying. These were further converted into pellets using extrusion-spheronization. The mean droplet size and zeta potential of L-SNEDDS were found to be 63.46 ± 2.12 nm and - 14.8 ± 3.11 mV while for solid SNEDDS pellets, these were 72.46 ± 2.16 nm and -38.7 ± 1.34 mV, respectively. The dissolution rate for curcumin and quercetin each was enhanced by 4.5 folds while permeability was enhanced by 5.28 folds (curcumin) and 3.35 folds (quercetin) when loaded into SNEDDS pellets. The Cmax for curcumin and quercetin containing SNEDDS pellets was found 532.34 ± 5.64 ng/mL and 4280 ± 65.67 ng/mL, respectively. This was 17.55 and 3.48 folds higher as compared to their naïve forms. About 50.23- and 5.57-folds increase in bioavailability was observed for curcumin and quercetin respectively, upon loading into SNEDDS pellets. SNEDDS pellets were found stable at accelerated storage conditions. The developed formulation was able to normalize the levels of blood glucose, lipids, antioxidant biomarkers, and tissue architecture of pancreas and liver in streptozotocin induced diabetic rats as compared to their naïve forms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Non-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 Covered: The 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 Opinion: NANEs 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.

Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h oscillation (sleep-wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an individual's circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.

Medical devices, being life-saving tools, are considered to be a boon for healthcare system. However, in addition to their therapeutic effects, there are several ill consequences that are caused by these devices. An effective cohort vigilant system was needed to manage such adverse effects. This had led to the introduction of materiovigilance. Materiovigilance is the study and follow-up of occurrences that arise as a result from the usage of the medical equipment. It not only manages adverse events (AE) but also creates harmonization among countries. Keeping these objectives in focus, the principles, perspectives, and practices with regard to materiovigilance that are followed in the USA, Europe, China, Japan, Australia, Canada, and India are being compared. Such a comparison is essential, which will help us to understand the gaps in the current regulatory systems in the above-mentioned countries and furthermore will provide a comprehensive picture to the regulatory authorities to amend any existing laws if required. These amendments may ensure optimal patient safety by providing them a benign experience from the use of medical devices., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colon cancer is characterised by the persistent change in bowel habits due to the formation of polyps (cancerous) in the inner lining of the colon. Clinically, there are several anticancer drugs available to treat colon cancer. Oxaliplatin (third generation platinum drug) is widely prescribed anticancer drug due to its broad range anticancer properties and low toxicities over cisplatin and carboplatin. Currently, use of oxaliplatin as adjuvant chemotherapy represents a standard care for the treatment of advanced colon cancer. Despite this, its rapid degradation in systemic circulations upon administration, lack of tumor specificity, and low bioavailability limits its anticancer potential. On the other hand, vanillic acid (VA) has shown anticancer potential in colon cancer by targeting mTOR/Ras pathway, HIF-1α inhibition, NF-ĸB, and Nrf2 that regulate cell growth, cell survival, proliferation and adaptation to cancer microenvironment. Normal oral delivery of these two drugs offers non-specific drug release in gastrointestinal tract that leads to unwanted toxicity and very less amount of drug become available for colonic site. Therefore, loading of these two drugs in polysaccharide based functionalized polymeric micelles (FPMs) can offer selective targeting at colonic site and could offer better therapeutic efficacy at much lesser doses of drugs. Therefore, a new hypothesis has been proposed that the combination of vanillic acid with oxaliplatin co-loaded in FPMs could provide colon targeting ability with enhanced potency and safety profile by targeting multiple pathways than current adjuvant chemotherapies available in the market for the treatment of colon cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current strategy to treat this disorder is based on the use of drugs that provide symptomatic relief. Most of these, however, exhibit numerous side effects and are not able to ameliorate all the signs and symptoms of PCOS. As dysbiosis is considered as one of the prime underlying causes of PCOS, restoration of eubiosis was considered as a plausible way to treat it. Bacteriotherpeutics like probiotics, synbiotics and even fecal microbiota transplant (FMT) have shown considerable effectiveness in PCOS. Of these baceteriotherapeutic options, FMT is considered to be the most holistic as it encompasses the bacteriome, virome, fungome, archaeome and even parasitome while both probiotics as well as synbiotics mainly comprise bacteria. Repeated FMT, however, is not a pragmatic option because of its inconvenience, lack of standardization, involved risk and scepticism amongst patients and physicians. If the eubiosis ushered by FMT is sustained for a long time, the repeated administrations of FMT can be avoided and maintenance therapy with any agent that can maintain the eubiotic condition can be adopted. Role of curcumin on gut microbiota is widely known. It is largely attributed to the ability of certain microbes to consume polyphenols as substrates and its positive effect on bacterial consumption of nutrients such as sugars. Based on various mechanisms and studies, a new hypothesis is being proposed wherein FMT and curcumin combination is predicted to be an effective and sustained treatment of PCOS with much lower rates of remission., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Huntington disease (HD) is a type of neurodegenerative disease that is characterized by presence of multiple repeats (more than 36) of cytosine-adenine-guanine (CAG) trinucleotides and mutated huntingtin (mHtt). This can further lead to oxidative stress, enhancement in level of ROS/RNS, mitochondrial dysfunction and neuroinflammations. Many clinical and preclinical trials have been conducted so far for the effective treatment of HD however, none of the drugs has shown complete relief. The regeneration of neurons is a very complicated process and associated with multiple pathological pathways. Hence, finding a unique solution using single drug that could act on multiple pathological pathways is really cumbersome. In the proposed hypothesis the use of demethyleneberberine (DMB) as a potential anti-HD agent has been explained. It is a metabolite of berberine and reported to act on multiple mechanistic pathways that are responsible for HD. Present article highlights new mechanistic insights through which DMB inhibits ROS/RNS, oxidative stress, mitochondrial dysfunctions and neuroinflammation such as NFκB, TNF-α, IL-6 and IL-8, cytokinin. Further its action on cellular apoptosis and neuronal cell death are also reported., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Immunomodulatory effects of macrolides in chronic inflammation are well known. In this study, we tested our hypothesis that azithromycin (AZT) can decrease inflammation in pediatric patients with sickle cell disease (SCD)., Methods: The use of AZT as an anti-inflammatory agent was evaluated in double-blind, placebo-controlled, cross-over study for 8 weeks of treatment with 8 weeks of washout. Blood samples were collected before (PRE) and after (POST) each 8-week treatment period. Repeated measures analysis of variance (ANOVA) with post hoc multiple comparison procedures and Chi-square test were used for statistical analysis of the data. Complete blood count, distribution of the lymphocyte subsets, and plasma levels of markers of vascular damage were analyzed., Results: A significant decrease in the number of leucocytes and granulocytes was observed in AZT group following treatment. An opposite dynamic was observed in placebo group; numbers of granulocytes significantly increased at POST interval. All markers of vascular damage were reduced in AZT group at POST interval with overall significance (P = 0.026). The most prominent significant changes were observed in levels of myeloid-related protein 8/14 (MRP8/14), lipocalin A (NGAL), matrix metalloproteinases (MMP) 9, and insulin-like growth factor-binding protein (IGFBP) 4. Plasma level of C-reactive protein (CRP) was significantly decreased in AZT group as well., Conclusions: Data suggested that AZT may be beneficial in management of microvascular injury in SCD., Competing Interests: Authors declare no conflict of interest., (Copyright 2021, Uchakin et al.)

Introduction : Diabetic retinopathy (DR) is associated with damage to the retinal blood vessels that lead eventually to vision loss. The existing treatments of DR are invasive, expensive, and cumbersome. To overcome challenges associated with existing therapies, various intraocular sustained release and novel drug delivery systems (NDDS) have been explored. Areas covered : The review discusses recently developed intraocular devices for sustained release of drugs as well as novel noninvasive drug delivery systems that have met a varying degree of success in local delivery of drugs to retinal circulation. Expert opinion : The intraocular devices have got very good success in providing sustained release of drugs in patients. The development of NDDS and their application through the ocular route has certainly provided an edge to treat DR over existing therapies such as anti-VEGF administration but their success rate is quite low. Moreover, most of them have proved to be effective only in animal models. In addition, the extent of targeting the drug to the retina still remains variable and unpredictable. The toxicity aspect of the NDDS has generally been neglected. In order to have successful commercialization of nanotechnology-based innovations well-designed clinical research studies need to be conducted to evaluate their clinical superiority over that of the existing 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

Background: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It is associated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. There are four stages of wound healing, namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In the case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Conventional dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer for many years., Introduction: In this review, the global prevalence as well as etiopathogenesis related to diabetic foot ulcer have been discussed. The potential role of various synthetic and herbal drugs, as well as their conventional dosage forms in the effective management of DFU have been discussed in detail., Methods: Structured search of bibliographic databases from previously published peer-reviewed research papers was explored and data has been represented in terms of various approaches that are used for the treatment of DFU., Results: About 148 papers, including both research and review articles, were included in this review to produce a comprehensive as well as a readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action., Conclusion: DFU has become one of the most common complications in patients having diabetes for more than ten years. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as the judicious selection of drugs as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemic or they have been repositioned. In clinical practice, much focus has been given to dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that combination therapy of herbal and synthetic drugs with multiple treatment pathways could be able to offer better management of DFU., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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 disease is 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Alzheimer's disease is type of dementia in which cognitive functions get declined. More than 50 million people are affected by this disease across the world. Many clinical and preclinical studies have been conducted on the treatment of AD but very limited number of drugs have found a clinical application. Because regeneration of neuron is a complicated process due to the involvement of multiple pathways, a combination of drugs that can work through multiple pathways could prove to be effective in treating AD. Based on prior studies and different mechanisms involved in the treatment, a new hypothesis has been proposed that a combination of galantamine, memantine and lycopene is anticipated to produce better activity as compared to the current therapies available in market for the treatment of this disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)