Konjac glucomannan: A comprehensive review of its extraction, health benefits, and pharmaceutical applications.

Konjac glucomannan (KG) is a dietary fiber hydrocolloid derived from Amorphophallus konjac tubers and is widely utilized as a food additive and dietary supplement. As a health-conscious choice, purified KG, along with konjac flour and KG-infused diets, have gained widespread acceptance in Asian and European markets. An overview of the chemical composition and structure of KG is given in this review, along with thorough explanations of the processes used in its extraction, production, and purification. KG has been shown to promote health by reducing glucose, cholesterol, triglyceride levels, and blood pressure, thereby offering significant weight loss advantages. Furthermore, this review delves into the extensive health benefits and pharmaceutical applications of KG and its derivatives, emphasizing its prebiotic, anti-inflammatory, and antitumor activities. This study highlights how these natural polysaccharides can positively influence health, underscoring their potential in various biomedical applications.

Development of engineered transferosomal gel containing meloxicam for the treatment of osteoarthritis.

OBJECTIVE: .In this study, we investigated the potential of meloxicam (MLX) developed as transferosomal gel as a novel lipidic drug delivery system to address osteoarthritis (OTA), a degenerative joint disease that causes pain and stiffness. By incorporating meloxicam into a transferosomal gel, our aim was to provide a targeted and efficient delivery system capable of alleviating symptoms and slowing down the progression of OTA. MATERIAL AND METHODS: Classical lipid film hydration technique was utilized to formulate different transferosomal formulations. Different transferosomal formulations were prepared by varying the molar ratio of phospholipon-90H (phosphodylcholine) to DSPE (50:50, 60:40, 70:30, 80:20, and 90:10) and per batch, 80mg of total lipid was used. The quality control parameters such as entrapment efficiency, particle size and morphology, polydispersity and surface electric charge, in vitro drug release, ex vivo permeation and stability were measured. RESULTS: The optimized transferosomal formulations revealed a small vesicle size (121±12nm) and greater MLX entrapment (68.98±2.3%). Transferosomes mediated gel formulation MLX34 displayed pH (6.3±0.2), viscosity (6236±12.3 cps), spreadability (13.77±1.77 gm.cm/sec) and also displayed sustained release pattern of drug release (81.76±7.87% MLX released from Carbopol-934 gel matrix in 24h). MLX34 revealed close to substantial anti-inflammatory response, with ∼81% inhibition of TNF-α in 48h. Physical stability analysis concluded that refrigerator temperature was the preferred temperature to store transferosomal gel. CONCLUSION: MLX loaded transferosomes containing gel improved the skin penetration and therefore resulted into increased inhibition of TNF-α level.

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies.

Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized and effective disease management. Identification of key driver mutations and molecular profiling have deepened our comprehension of the genetic alterations in colorectal cancer, facilitating targeted therapy and immunotherapy selection. Biomarkers such as microsatellite instability (MSI) and DNA mismatch repair deficiency (dMMR) guide treatment decisions, opening avenues for immunotherapy. Emerging technologies such as liquid biopsies, artificial intelligence, and machine learning promise to revolutionize early detection, monitoring, and treatment selection in precision medicine. Despite these advancements, ethical and regulatory challenges, including equitable access and data privacy, emphasize the importance of responsible implementation. The dynamic nature of colorectal cancer, with its tumor heterogeneity and clonal evolution, underscores the necessity for adaptive and personalized treatment strategies. The future of precision medicine in colorectal cancer lies in its potential to enhance patient care, clinical outcomes, and our understanding of this intricate disease, marked by ongoing evolution in the field. The current reviews focus on providing in-depth knowledge on the various and diverse approaches utilized for precision medicine against colorectal cancer, at both molecular and biochemical levels.

Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives.

This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including the complexities involved and the perspectives on how to navigate them. In the realm of nanomedicines, ensuring the safety of nanomaterials is paramount due to their unique characteristics and potential interactions with biological systems. Regulatory bodies are actively formulating guidelines and standards to assess the safety and risks associated with nanomedicine products, emphasizing the need for standardized characterization techniques to accurately gauge their safety and effectiveness. Regarding gene vaccines, regulatory frameworks must be tailored to address the distinct challenges posed by genetic interventions, necessitating special considerations in safety and efficacy evaluations, particularly concerning vector design, target specificity, and long-term patient monitoring. Ethical concerns such as patient autonomy, informed consent, and privacy also demand careful attention, alongside the intricate matter of intellectual property rights, which must be balanced against the imperative of ensuring widespread access to these life-saving treatments. Collaborative efforts among regulatory bodies, researchers, patent offices, and the private sector are essential to tackle these challenges effectively, with international cooperation being especially crucial given the global scope of nanomedicine and genetic vaccine development. Striking the right balance between safeguarding intellectual properties and promoting public health is vital for fostering innovation and ensuring equitable access to these ground-breaking technologies, underscoring the significance of addressing these regulatory hurdles to fully harness the potential benefits of nanomedicine and gene vaccines for enhancing healthcare outcomes on a global scale. STATEMENT OF SIGNIFICANCE: Several biomaterials are being proposed for the development of nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, to quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since the US Food and Drug Administration (FDA) approval of Pfizer and Moderna's COVID-19 vaccines, raising public awareness to the regulatory challenges associated with nanomedicines and genetic vaccines. This review provides insights into the current perspectives and potential strategies for addressing these issues, including clinical trials. By navigating these regulatory landscapes effectively, we can unlock the full potential of nanomedicine and genetic vaccines using a range of promising biomaterials towards improving healthcare outcomes worldwide.

A multi-modal approach to investigate Desmodium gangeticum's influence on stress-induced male infertility: In vivo, in vitro, and in silico assessments.

Physical and psychological stress has an inverse relation with male libido and sperm quality. The present study investigates the potential fertility-enhancing properties of Desmodium gangeticum (DG) root extracts in male Wister rats subjected to immobilization-induced stress (SIMB). DG roots were extracted using n-hexane (HEDG), chloroform (CEDG), and water (AEDG). In the pilot study, aphrodisiac protentional was investigated at two doses (125 and 250 mg kg-1) of each extract. In the main study, the HEDG and AEDG at 125 and 250 mg kg-1 were challenged for the stress by immobilization (SIMB), for 6 h daily over 28 days. Parameters assessed included aphrodisiac effects, gonadosomatic index (GSI), semen quality, sperm quantity, fructose content, serum hormonal levels, testicular oxidative stress, and testicular histopathology. Additional in silico studies, including the lipid solubility index, molecular docking, molecular dynamics, and SymMap studies were conducted for validation. HEDG demonstrated significant aphrodisiac activity, improved - GSI, sperm quality and quantity, and fructose content, serum testosterone levels, histological changes induced by SIMB in the testes. Swiss ADME studies indicated Gangetin (a pterocarpan) had a high brain permeation index (4.81), a superior docking score (-8.22), and higher glide energy (-42.60), compared with tadalafil (-7.17). The 'Lig fit Prot' plot in molecular dynamics simulations revealed a strong alignment between Gangetin and phosphodiesterase type 5 (PDE5). HEDG exerts aphrodisiac effects by increasing blood testosterone levels and affecting PDE5 activity. The protective effects on spermatozoa-related parameters and testicular histological changes are attributed to the antioxidant and anti-inflammatory properties, of pterocarpan (gangetin).

Multi-faceted Anti-obesity Effects of N-Methyl-D-Aspartate (NMDA) Receptor Modulators: Central-Peripheral Crosstalk.

Hypothalamus is central to food intake and satiety. Recent data unveiled the expression of N-methyl-D-aspartate receptors (NMDAR) on hypothalamic neurons and their interaction with GABAA and serotoninergic neuronal circuits. However, the precise mechanisms governing energy homeostasis remain elusive. Notably, in females, the consumption of progesterone-containing preparations, such as hormonal replacement therapy and birth control pills, has been associated with hyperphagia and obesity-effects mediated through the hypothalamus. To elucidate this phenomenon, we employed the progesterone-induced obesity model in female Swiss albino mice. Four NMDAR modulators were selected viz. dextromethorphan (Dxt), minocycline, d-aspartate, and cycloserine. Obesity was induced in female mice by progesterone administration for 4 weeks. Mice were allocated into 7 groups, group-1 as vehicle control (arachis oil), group-2 (progesterone + arachis oil), and group-3 as positive-control (progesterone + sibutramine); other groups were treated with test drugs + progesterone. Various parameters were recorded like food intake, thermogenesis, serum lipids, insulin, AST and ALT levels, organ-to-body weight ratio, total body fat, adiposity index, brain serotonin levels, histology of liver, kidney, and sizing of fat cells. Dxt-treated group has shown a significant downturn in body weight (p < 0.05) by a decline in food intake (p < 0.01), organ-to-liver ratio (p < 0.001), adiposity index (p < 0.01), and a rise in body temperature and brain serotonin level (p < 0.001). Dxt demonstrated anti-obesity effects by multiple mechanisms including interaction with hypothalamic GABAA channels and anti-inflammatory and free radical scavenging effects, improving the brain serotonin levels, and increasing insulin release from the pancreatic ß-cells.

Lab on chip based self-adjustable liposomes for rapid wound healing: An in depth in vitro, in vivo and higher dose toxicity investigation.

Thanks to microfluidic technology, different nano-delivery systems are becoming clinically viable. Using a novel and rapid microfluidic hydrodynamic focusing (MHF) method (lipids on chip) we developed self-adaptable liposomes (SLs) containing cefpodoxime proxetil (CP) for the treatment of skin infections caused by Staphylococcus aureus. SLs were optimized using different flow rate ratios in the MHF method and the final formulation CPT3 was found to be the best in terms of particle size (68.27 ± 01.15 nm), % entrapment efficiency (% EE: 82 ± 1.5), polydispersity (PDI: 0.2 ± 0.012), and degree of deformability (DOD: 4.7 ± 0.18 nm). Rats (Sprague Dawley) treated with a self-adaptable CPT3 liposomal formulation recuperate skin injury, exhibited reduced bacterial counts (<106 CFU/mL) in the wounded region, and completely restored (100 %) on day 21. Rat survival, in vivo dermal pharmacokinetics and ex vivo-in vivo relationship were also investigated. Rats treated with an even 10-fold higher dose (100 mg/kg/day) of CP using an equivalent CPT3 formulation did not show any symptoms of toxicity as revealed by hematological, biochemical, and internal organ assessment observations. Finally, the developed CPT3 formulation with special interest in patients with high-risk skin injuries not only delivered CP in a controlled manner but was also clinically effective and safe as it did not produce any serious adverse events even at 10× higher doses in the infected rats.

D-optimal mixture design inspired modified release tablet formulation of lamotrigine for the treatment of seizures: An in-depth characterization.

OBJECTIVE: Lamotrigine (LTG) an anticonvulsant drug with a dissociation constant (pKa: 5.7), suffers from enhanced blood plasma spike after each dose, when administered as fast release tablet. Being BCS class-II candidate and pH dependent solubility, development of release-controlled tablets of LTG is a major challenge. This investigation aims at designing the release-controlled tablet (RCT) formulation of LTG using a solid dispersion (SD) technique via addressing its solubility and release problems. MATERIAL AND METHODS: RCT of LTG was fabricated using SD blend of Eudragit RL and Eudragit RS and PVP K-30 with different polymer blend ratio (1:5 and 1:7). The optimization of RCT of LTG was performed using D-optimal mixture design with three independent variables, three response variables, and one constraint. The dissolution rate was determined and data were then fitted to different mathematical models. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies and tableting parameters were analyzed. RESULT: In vitro studies of predicted optimized batches (POBs) have shown that drug release over a period of 12hours was 88.05±3.4% in media I, 86.10±3.7% in media II and 85.84±4.2% in media III. An in vitro kinetic model equating R2-value for all the tested models indicated that the first order and Higuchi release kinetics model were the most appropriate. CONCLUSION: Based on the optimized formulation consisting of SD of LTG with Eudragit RL, Eudragit RS and PVP K-30, the release rate was consistently similar throughout the GI tract, regardless of the pH of the environment.

Niosomes based formulation containing tenoxicam: A newer solution for the rheumatic diseases.

OBJECTIVE: This investigation aimed to explore the potential of non-ionic surfactant based niosomal vesicles encapsulating tenoxicam (TN; anti-rheumatic drug) for the treatment of rheumatic diseases. MATERIAL AND METHODS: Mechanical dispersion technique with controlled pressure was employed to prepare different niosomal formulations. The effects of different ratios of surfactant (span-60), lipid, and sodium deoxycholate on noisome's physicochemical properties have been examined. Moreover, inhibition of TNF-α in lipopolysaccharide-activated cultured Human leukemia monocytic (THP-1) cells were demonstrated to assess the in vitro inflammation profile. Finally, the optimized niosomal formulation (TN3) was prepared in gel matrix consist of carbopol 934 (termed as TN34) and stability was also tested at 4±2 ÌŠC, 25±2 ÌŠC, 37±2 ÌŠC and 45±2 ÌŠC for 6 months. RESULTS: The optimized niosomal formulation exhibited a small vesicle size (165±14nm) and high drug encapsulation (79.64±1.5%). Niosomal gel formulation TN34 showed pH (6.7), viscosity (6810±3.34 cps), spreadability (19.11±1.87gm.cm/sec) and also displayed sustained release pattern of drug release (98.16±0.07% TN released from gel matrix in 24h) in vitro release study. TN34 exhibited substantial anti-inflammatory response, with ∼75% inhibition of TNF-α in 48h. Stability investigation revealed that refrigerator temperature is most suitable for the storage of niosomal gel. CONCLUSION: Transdermal niosomal formulation displayed promising potential in the treatment of rheumatic diseases.

Quality-by-design-based engineered liposomal nanomedicines to treat cancer: an in-depth analysis.

Engineered nano-sized liposomes have attained the highest success rate in commercialization among the reported nanomedicines. However, developing industrially acceptable nanoliposomes is still challenging because the process, formulation factors and even their properties may critically influence the desired attributes of the final nanoliposomal product. Implementation of quality-by-design (QbD) in nanoliposomal fabrication has led to revolutionary advancement int better analysis of the interacting factors (drug and lipid ratio, hydration, sonication, etc), which, in turn, leads to better product performance with predefined attributes (entrapment efficiency percentage, drug release time and pattern, vesicles size, polydispersity index, surface charge and surface morphology). This review provides a summary of decade of research and an in-depth analysis of QbD-based nanoliposomes developed to address different cancers. The review aims to provide complete details of QbD-inspired nanoliposomal development from process to application.

This review describes liposomal nanomedicines manufactured via applying quality-by-design (QbD) principals/methods for the treatment of cancer. QbD is industrially applicable technique of manufacturing for emerging pharmaceutical nano-formulations owing to its benefits, including reduced cost, a smaller number of trials, high risk assessment and control over different formulation factors.

'Transfersome-embedded-gel' for dual-mechanistic delivery of anti-psoriatic drugs to dermal lymphocytes.

AIM: Develop a platform for co-delivering clobetasol propionate (CP) and cyclosporine (CyA) to the epidermis and dermis to treat psoriasis. METHODS: The transfersomes were prepared by thin-film hydration method. Transfersomes were characterised by dynamic light scattering and transmission electron microscope (TEM). Then, the gel stability, viscosity, pH, and spreadability were measured. Cytotoxicity of the CyA-loaded transfersome embedded in CP-dispersed gel (TEG-CyA-CP) was assessed on both human keratinocyte cell line (HaCaT) and Jurkat cells. In vitro cellular uptake and ex vivo dermal distribution was measured. The expression of inflammatory markers was assessed by reverse-transcription PCR (RT-PCR). RESULTS: Nanoscale (<150 nm) transferosomes with high CyA encapsulation efficiency (>86%) were made. TEG-CyA-CP demonstrated higher viscosity (4808.8 ± 12.01 mPas), which may help control dual drug release. Ex vivo results showed TEG-CyA-CP ability to deliver CyA in the dermis and CP in the epidermis. RT-PCR studies showed the optimised formulation helps reduce the tumour necrosis factor (TNF-α) and interleukin-1 (IL-1) levels to relieve psoriasis symptoms. CONCLUSION: The developed TEG-CyA-CP represents a promising fit-to-purpose delivery platform for the dual-site co-delivery of CyA and CP in treating psoriasis.

Laser activatable nanographene colloids for chemo-photothermal combined gene therapy of triple-negative breast cancer.

This investigation reports the green approach for developing laser activatable nanoscale-graphene colloids (nGC-CO-FA) for chemo-photothermal combined gene therapy of triple-negative breast cancer (TNBC). The nano colloid was found to be nanometric as characterized by SEM, AFM, and zeta sizer (68.2 ± 2.1 nm; 13.8 ± 1.2 mV). The doxorubicin (Dox) loaded employing hydrophobic interaction/π-π stacking showed >80% entrapment efficiency with a sustained pH-dependent drug release profile. It can efficiently incorporate siRNA and Dox and successfully co-localize them inside TNBC cells to obtain significant anticancer activity as evaluated using CCK-8 assay, apoptosis assay, cell cycle analysis, cellular uptake, fluorescence assay, endosomal escape study, DNA content analysis, and gene silencing efficacy studies. nGC-CO-FA/Dox/siRNA released the Dox in temperature- and a pH-responsive manner following NIR-808 laser irradiation. The synergistic photo-chemo-gene therapy using near infrared-808 nm laser (NIR-808) irradiation was found to be more effective as compared to without NIR-808 laser-treated counterparts (∆T: 37 ± 1.1 °C → to 49.2 ± 3.1 °C; 10 min; 0.5 W/cm2), suggesting the pivotal role of photothermal combined gene-therapy in the treatment of TNBC.

Recent advancements and future submissions of silica core-shell nanoparticles.

The core-shell silica-based nanoparticles (CSNPs) possess outstanding properties for developing next-generation therapeutics. CSNPs provide greater surface area owing to their mesoporous structure, which offers a high opportunity for surface modification. This review highlights the potential of core-shell silica-based nanoparticle (CSNP) based injectable nanotherapeutics (INT); its role in drug delivery, biomedical imaging, light-triggered phototherapy, Plasmonic enhancers, gene delivery, magnetic hyperthermia, immunotherapy, and potential as next-generation theragnostic. Specifically, the conceptual crosstalk on modern synthetic strategies, biodistribution profiles with a mechanistic view on the therapeutics loading and release modeling are dealt in detail. The manuscript also converses the challenges associated with CSNPs, regulatory hurdles, and their current market position.

Development of an Aloe vera-based Emulgel for the Topical Delivery of Desoximetasone

Objectives: Desoximetasone (DMS) is a widely recommended drug for the topical treatment of plaque psoriasis. However, low water solubility and short half life of DMS present major obstacles in the development of an effective topical formulation. Thus, there is a demand for the development of a safe and effective topical system to deliver hydrophobic DMS. The present study aimed to develop an Aloe vera-based emulgel formulation to ensure enhanced skin deposition of DMS for effective treatment of plaque psoriasis. Materials and Methods: Different formulations (DE1-DE4) of Aloe vera emulgel were prepared using dispersion technique, wherein varying concentrations of propylene glycol (6-14% w/w) and carbopol 934 (0.5-1.0% w/w) were used. Results: Zetasizer measurements revealed that the globule size of the formulations ranged from 10.34 µm±0.9 to 14.60 µm±1.4 (n=50). Extrudability analysis for the DE3 and DE2 formulations revealed an extrudability of 5.6±0.11 g/cm2 and 5.8±0.13 g/cm2, respectively. The pH of the formulations was recorded in the range of 5.8-6.8. Among these formulations, DE3 showed a maximum drug content of 94.64%±0.29 (n=3), and thus was used for further in vitro evalutions. A texture analyzer showed that an optimized DE3 formulation was firmer and exhibited optimal spreadability in comparison with the DE2 formulation. For DE3, the mean max force that represented "firmness" was recorded to be 833.37 g, where as the mean area, denoting "work of shear", was 324.230 g.sec. The DE3 formulation exhibited DMS permeation of 95.40±1.6% over a period of 7 h, as detrmined using an in house fabricated Franze diffusion cell. Evaluation of in vitro release kinetics revealed that the release of DMS fitted into the Korsmeyer-Peppas model. Conclusion: Physicochemical characteristics and enhanced in vitro permeation of DMS from Aloe vera emulgel highlight its suitability to be efficiently employed for the topical treatment of skin ailments.

Multifunctional polymeric micellar nanomedicine in the diagnosis and treatment of cancer.

Polymeric micelles are a prevalent topic of research for the past decade, especially concerning their fitting ability to deliver drug and diagnostic agents. This delivery system offers outstanding advantages, such as biocompatibility, high loading efficiency, water-solubility, and good stability in biological fluids, to name a few. The multifunctional polymeric micellar architect offers the added capability to adapt its surface to meet the looked-for clinical needs. This review cross-talks the recent reports, proof-of-concept studies, patents, and clinical trials that utilize polymeric micellar family architectures concerning cancer targeted delivery of anticancer drugs, gene therapeutics, and diagnostic agents. The manuscript also expounds on the underlying opportunities, allied challenges, and ways to resolve their bench-to-bedside translation for allied clinical applications.

Discovery of boronic acid-based potent activators of tumor pyruvate kinase M2 and development of gastroretentive nanoformulation for oral dosing.

Several studies have established that cancer cells explicitly over-express the less active isoform of pyruvate kinase M2 (PKM2) is critical for tumorigenesis. The activation of PKM2 towards tetramer formation may increase affinity towards phosphoenolpyruvate (PEP) and avoidance of the Warburg effect. Herein, we describe the design, synthesis, and development of boronic acid-based molecules as activators of PKM2. The designed molecules were inspired by existing anticancer scaffolds and several fragments were assembled in the derivatives. 6a-6d were synthesized using a multi-step synthetic strategy in 55-70% yields, starting from cheap and readily available materials. The compounds were selectively cytotoxic to kill the cancerous cells at 80 nM, while they were non-toxic to the normal cells. The kinetic studies established the compounds as novel activators of PKM2 and (E/Z)-(4-(3-(2-((4-chlorophenyl)amino)-4-(dimethylamino)thiazol-5-yl)-2-(ethoxycarbonyl)-3-oxoprop-1-en-1-yl) phenyl)boronic acid (6c) emerged as the most potent derivative. 6c was further evaluated using various in silico tools to understand the molecular mechanism of tetramer formation. Docking studies revealed that 6c binds to the PKM2 dimer at the dimeric interface. Further to ascertain the binding site and mechanism of action, rigorous MD (molecular dynamics) simulations were undertaken, which led to the conclusion that 6c stabilizes the center of the dimeric interface that possibly promotes tetramer formation. We further planned to make a tablet of the developed molecule for oral delivery, but it was seriously impeded owing to poor aqueous solubility of 6c. To improve aqueous solubility and retain 6c at the lower gastrointestinal tract, thiolated chitosan-based nanoparticles (TCNPs) were prepared and further developed as tablet dosage form to retain anticancer potency in the excised goat colon. Our findings may provide a valuable pharmacological mechanism for understanding metabolic underpinnings that may aid in the clinical development of new anticancer agents targeting PKM2.

Employment of Quality by Design Approach via Response Surface Methodology to Optimize and Develop Modified-release Formulation of Hydrochlorothiazide.

BACKGROUND: Heart attack predominantly occurs during the last phase of sleep and early morning hours, causing millions of death worldwide. Hydrochlorothiazide (HCTZ) is a recommended drug for the prevention of heart disease, but its long action (>4 h) dosage form is lacking in the commercial market and development of modified-release formulation may have industrial significance. Regulatory agencies emphasize Quality by Design based approach for product development to entrust quality in the product. OBJECTIVE: The current research aimed to develop a quality product profile of HCTZ modifiedrelease tablets (MRT; ~14 h) by applying Response Surface Methodology using the computational QbD approach. METHODS: Three independent factors were identified by qualitative and quantitative risk assessment. Statistical terms like p-value, lack of fit, the sum of square, R-squared value, model F value, and linear equations were determined. Graphical tools like normal plot of residual, residual vs predicted plot and box cox plot were used to verify the model selection. The graphical relationship among the critical, independent variables was represented using the Contour plot and 3-D surface plot. Design space was identified by designing an overlay plot using response surface design. RESULTS: Excellent correlation was observed between actual and predicted values. Similarity Factor (F2) of reproducible trials was 78 and 79, and content uniformity was 100.9% and 100.4%. Average weight, hardness, thickness, diameter, and friability were within acceptable limits. CONCLUSION: QbD approach, along with a quality risk management tool, provided an efficient and effective paradigm to build quality MRT of HCTZ.

Niacinamide May Be Associated with Improved Outcomes in COVID-19-Related Acute Kidney Injury: An Observational Study.

Background: AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods: We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT. Results: A total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P=0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P=0.03; P interaction with KDIGO stage=0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P=0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction=0.03). Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.

Green graphene nanoplates for combined photo-chemo-thermal therapy of triple-negative breast cancer.

Aim: Green graphene oxide (GO) nanoplates, which are reduced and stabilized by quercetin and guided by folate receptors (quercetin reduced and loaded GO nanoparticles-folic acid [FA]), were developed to mediate combined photo-chemo-thermal therapy of triple-negative breast cancer. Materials & methods: Modified Hummers method was used for the synthesis of GO followed by its reduction using quercetin, FA was then conjugated as a targeting ligand. A cytotoxicity assay, apoptosis assay and cellular uptake assay were performed in vitro in MDA-MB-231 cell line with and without irradiation of a near-infrared 808 nm laser. Results & conclusion: Quercetin reduced and loaded GO nanoparticles-FA showed significantly high cellular uptake (p < 0.001) and cytotoxic effects in MDA-MB-231 cells, which was even more prominent under the situation of near-infrared 808 nm laser irradiation, making it a potential option for treating triple-negative breast cancer.

Advanced nanoscale carrier-based approaches to overcome biopharmaceutical issues associated with anticancer drug 'Etoposide'.

Etoposide (ETS), topoisomerase-II inhibitor, is a first-line anticancer therapeutics used in diverse cancer types. However, the therapeutic potential of this molecule has mainly impeded due to its detrimental toxicity profile, unfavorable rejection by the cancer cells due to P-glycoprotein (P-gp) efflux activity, and rapid hepatic clearance through extensive metabolism by Cytochrome-P450. To increase the therapeutic potency without significant adverse effects, the implication of novel ETS-nanoformulation strategies have recommended mainly. Nanomedicine based nanoformulation approaches based on nanoparticles (NPs), dendrimers, carbon-nanotubes (CNTs), liposomes, polymeric micelles, emulsions, dendrimers, solid-lipid NPs, etc offers immense potential opportunities to improve the therapeutic potential of pharmaceutically problematic drugs. This review provides an up-to-date argument on the work done in the field of nanomedicine to resolve pharmacokinetic and pharmacodynamic issues associated with ETS. The review also expounds the progress in regards to the regulatory, patenting and clinical trials related to the innovative formulation aspects of ETS.