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Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS. [ABSTRACT FROM AUTHOR]

Erlotinib is a reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that acts by inhibiting signaling pathways, resulting in the disruption of cancerous cell proliferation. Erlotinib is a promising anticancer agent mainly utilized in the mitigation of non-small cell lung cancer cells (NSCLC) and pancreatic tumor. Apart from NSCLC and pancreatic tumor, erlotinib has also been employed in different malignancies, including metastatic colorectal cancer, malignant glioma, breast cancer, gastrointestinal cancers, etc. Despite erlotinib's distinctive qualities as a targeted drug, its applications are still limited by poor solubility, variable oral bioavailability, a high daily dose requirement, large protein binding, and primitive or acquired therapeutic resistance. Nanotechnology is a favorable approach to increase therapeutic effectiveness of erlotinib. It is one of the newest scientific field directed toward the diagnosis and targeted treatment of cancer. This technology aids in the distinction between normal and malignant cells, which overlays the strategy for targeted delivery. This manuscript discussed the advances of erlotinib nanoformulations in the management of different cancers. Moreover, the manuscript also comprises various research outcomes of erlotinib nanoformulations with other therapeutic agents as combinational therapy. Erlotinib can be delivered to a precise target in the body utilizing different polymers, lipids, and metals. [ABSTRACT FROM AUTHOR]

Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The chronic respiratory non-communicable diseases, asthma and chronic obstructive pulmonary disease (COPD) are among the leading causes of global mortality and morbidity. Individuals suffering from these diseases are particularly susceptible to respiratory infections caused by bacterial and/or viral pathogens, which frequently result in exacerbation of symptoms, lung function decline, frequent hospital emergency visits and increased socioeconomic burden. Human rhinoviruses (HRV) remain the major viral pathogen group implicated in exacerbations of both asthma and COPD. The rhinoviral entry into the host lung epithelium is facilitated primarily by the adhesion site ("receptor") intercellular adhesion molecule-1 (ICAM-1), coincidentally expressed on the respiratory epithelium in these conditions. Multiple observations of increased airway ICAM-1 protein in asthmatics, smokers and smoking-related COPD have been recorded in the literature. However, the lack of robust therapies for COPD in particular has triggered a renewed interest in assessing receptor antagonism-based anti-viral strategies for treatment of intercurrent viral infections in those with pre-existing chronic lung diseases. Given the crucial role ICAM-1 plays in facilitating HRV adhesion and, thus, transmissibility to the host respiratory system, as well as the up-regulation of ICAM-1 by smoking, we summarize the role of HRV in smoking-induced COPD and especially highlight the role of ICAM-1 in epithelial viral adhesion and chronic lung disease progression. Further, the review also sheds light specifically on evolving precision therapeutic strategies in blocking ICAM-1 for preventing viral adhesion and exacerbations of COPD. [ABSTRACT FROM AUTHOR]

The present study was aimed to develop and optimize nanoliposomes of gefitinib for effective tumor targeting. Central composite design was used to study the effect of formulation variables: sonication time, Tween 80/soya lecithin ratio, and cholesterol/soya lecithin ratio on particle size and entrapment efficiency. Gefitinib-loaded nanoliposomes were prepared using modified emulsification and ultrasonic method. The nanoliposomes of optimized batch (GF16) were found ellipsoidal or quasi-spherical in shape, with an average size of 99.88 nm and highest entrapment efficiency (88.91 ± 0.6758%). In comparison to the marketed formulation, the optimized batch released gefitinib in a sustained manner (80.16 ± 0.4849%) in 24 h following the Korsemeyer-Peppas' model, in a mechanism combining Fickian diffusion and liposome relaxation. Furthermore, the cytotoxicity assay revealed gefitinib-loaded nanoliposomes had reduced cytotoxicity as compared to free drug in A549 and H1299 cells with an IC50 value 9.32 ± 1.25 and 8.54 ± 1.08 µM, respectively. The significant cytotoxic response of the developed nanoliposomes may be attributed due to its low particle size, high entrapment efficiency, and prolonged drug release profile. Nanoliposomes had favorable physical stability when stored at a temperature of 4 °C. Overall, the developed nanoliposomes may be considered as a promising anticancer formulation, which needs further clinical investigations and may provide a new direction to the cancer clinics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health. [ABSTRACT FROM AUTHOR]

Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients. [ABSTRACT FROM AUTHOR]

The present study was designed to develop and validate a high-performance thin-layer chromatography (HPTLC) system for the simultaneous quantitative determination of berberine and rutin in Tinospora cordifolia extract and their pharmaceutical preparations. Chromatographic development was done using a blend of n-hexane, ethyl acetate, glacial acetic acid and methanol (10:1.1:1.1:2.5, v/v) as the mobile phase. Detection was completed densitometrically at 254 nm. The RF estimation of berberine and rutin was observed to be 0.67 ± 0.02 and 0.47 ± 0.02, respectively. The developed HPTLC method was validated according to ICH guidelines; the method was specific, linear and accurate and can be used to determine berberine and rutin in marketed herbal preparations. The Tinospora cordifolia plant extract was further evaluated for antioxidant activity using HPTLC, and berberine was found to be more active than rutin during DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity. The method was found simple, rapid, accurate, specific and robust for the analysis of berberine and rutin in crude drug using the same method. [ABSTRACT FROM AUTHOR]

The complete correct name should read as follows Dinesh Kumar Chellappan The original article has been corrected. Correction to: Inflammopharmacology (2022) 30:725-735 https://doi.org/10.1007/s10787-022-0096... The 7th author name has been incorrectly published in the original publication. [Extracted from the article]

An in silico approach through decision tree (DT) and moving average analysis (MAA) has been employed for development of models for prediction of anti-inflammatory activity. A data set consisting of 44 analogues of 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles was selected for this study. These compounds act as anti-inflammatory agents through inhibition of tumor progression loci-2 (Tpl2) kinase and tumor necrosis factor-α (TNF-α) production. A total of 44 descriptors of diverse nature, from a large pool of molecular descriptors calculated through E- Dragon software (version 1.0) and an in-house computer program were selected for further analysis. DT was used to determine the importance of molecular descriptors. DT identified two topological indices as most important and classified the analogues involved in the data set with an accuracy of ~91% in training set and ~66% in 10 fold cross validated set. Three independent models were also developed through MAA. Accuracy of prediction of these models varied from 87.5 to 92.5%. The statistical significance of proposed models was assessed through intercorrelation analysis, sensitivity, specificity, and Matthew's correlation coefficient. The proposed models offer a vast potential for providing lead structures for development of potent anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

The relationship between the topochemical indices and poly(ADP-ribose) polymerase inhibitory activity of indole-1-ones has been investigated. Wiener’s topochemical index, a distance-based topochemical descriptor; molecular connectivity topochemical index, an adjacency-based topochemical descriptor; and superadjacency topochemical index, an adjacency-cum-distance–based topochemical descriptor, were used for the present investigation. The values of Wiener’s topochemical index, molecular connectivity topochemical index, and superadjacency topochemical index for each of 41 analogs comprising the data set were computed via an in-house computer program. Resulting data were analyzed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned to each analog involved in the data set using these models, which was then compared with the reported poly(ADP-ribose) polymerase inhibitory activity. Statistical analysis revealed that two of the three models were not intercorrelated. Accuracy of prediction of these models varied from approximately 83% to 85%. [ABSTRACT FROM AUTHOR]

New-generation highly discriminating topological descriptors, termed superaugmented eccentric connectivity indices ( SA ξc), have been conceptualized in the present study. The values of SA ξc for all the possible structures of three, four, and five vertices were computed using an in-house computer program. The sensitivity to branching, discriminating power, and degeneracy of SA ξc were investigated for all the possible structures of three, four, and five vertices and subsequently compared with those of the eccentric and augmented eccentric connectivity indices. The proposed superaugmented eccentric connectivity indices exhibited high sensitivity towards branching, exceptionally high discriminating power, and extremely low degeneracy. The superaugmented eccentric connectivity index-3 ( SA ξc 3) exhibited an exceptionally high discriminating power of > 4000 for all possible structures containing only five vertices. The statistical significance of the proposed indices was investigated using intercorrelation analysis with Wiener’s index; Balaban’s J index (the average distance sum connectivity); the molecular connectivity index; the eccentric connectivity index; and the augmented eccentric connectivity index values. The high sensitivity to branching and exceptionally high discriminating power amalgamated with extremely low degeneracy give these indices vast potential for isomer discrimination, similarity/dissimilarity, drug design, quantitative structure–activity/structure–property relationships, lead optimization, and combinatorial library design. [ABSTRACT FROM AUTHOR]

Lung cancer is the notable cause of cancer associated deaths worldwide. Recent studies revealed that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs (-2 and -9) play an important part in tumor development and angiogenesis, which suggests that creating potent MMP-2 and -9 inhibitors, should be an important goal in lung cancer therapy. In the present study, an effort has been made to develop new anti-metastatic and anti-invasive agents, wherein a series of novel diazepine substituted cinnamic acid derivatives were designed, synthesized and assayed for their inhibitory activities on MMP-2 and MMP-9. These derivatives were prepared via microwave assisted reaction of tert-butyl (3-cinnamamidopropyl)carbamate derivatives mixed with 2,3-dibromopropanoic acid and potassium carbonate was added to obtain 4-(tert-butoxycarbonyl)-1-cinnamoyl-1,4-diazepane-2-carboxylic acid derivatives. The newly synthesized compounds were characterized by IR, NMR and mass spectroscopy. All the tested compounds showed good to excellent cytotoxic potential against A549 human lung cancer cells. The active compounds displaying good activity were further examined for the inhibitory activity against MMPs (-2 and -9). In addition, the structure and anticancer activity relationship were further supported by in silico docking studies of the active compounds against MMP-2 and MMP-9. [ABSTRACT FROM AUTHOR]