Anti-cancer properties of Sansalvamide A, its derivatives, and analogs: an updated review.

As peptide-based therapies gain recognition for their potential anti-cancer activity, cyclic peptides like Sansalvamide A, a marine-derived cyclic depsipeptide, have emerged as a potential anti-cancer agent due to their potent activity against various cancer types in preclinical studies. This review offers a comprehensive overview of Sansalvamide A, including its sources, structure-activity relationship, and semi-synthetic derivatives. The review also aims to outline the mechanisms through which Sansalvamide A and its analogs exert their anti-proliferative effects and to discuss the need for enhancements in pharmacokinetic profiles for better clinical utility. An extensive literature search was conducted, focusing on studies that detailed the anti-cancer activity of Sansalvamide A, its pharmacokinetics, and mechanistic pathways. Data from both in vitro and in vivo studies were collated and analyzed. Sansalvamide A and its analogs demonstrated significant anti-cancer activity across various cancer models, mediated through Hsp 90 inhibition, Topoisomerase inhibition, and G0/G1 cell cycle arrest. However, their pharmacokinetic properties were identified as a significant limitation, requiring improvement for effective clinical translation. Despite its notable anti-cancer effects, the utility of Sansalvamide A is currently limited by its pharmacokinetic characteristics. Therefore, while Sansalvamide A exhibits promise as an anti-cancer agent, there is a compelling need for further clinical and toxicological studies and optimization of its pharmacokinetic profile to fully exploit its therapeutic potential alongside modern cancer therapies.

Nanobiosensors: Concepts and emerging clinical applications.

Biosensors have been one of the most fascinating topics for scientists for a long time. This is because biological moieties are multifaceted and are unswervingly related to the presence of a healthy atmosphere. The biosensor approach has also endured profound changes in recent years. Biosensors have been emphasized for various applications, including food quality estimation, surveillance systems, and health and metabolic abnormality diagnostics. The advances in nanotechnology have led to a considerable potential to enhance biosensors' sensitivity, robustness, and anti-interference capabilities. Several new nanomaterials (such as nanoparticles, nanotubes, nanorods, and nanowires) have been fabricated due to the evolution of nanotechnology, and their unique features are gradually being identified, allowing for much faster detection and reproducibility. Biosensor performance has also been enhanced substantially as a result of their use. Because of their capacity to detect a wide range of compounds at deficient concentrations, nanobiosensors have sparked much interest. This article discusses biosensors based on various nanomaterials, their evolution, accompanying features, and their applications in multiple fields.

Pharmaceutical/Biomedical applications of electrospun nanofibers - Comprehensive review, attentive to process parameters and patent landscape.

Nanotechnology is a new science and business endeavour with worldwide economic benefits. Growing knowledge of nanomaterial fabrication techniques has increased the focus on nanomaterial preparation for various purposes. Nanofibers are one-dimensional nanomaterials having distinct physicochemical properties and characteristics. Nanofibers are nanomaterial types with a cross-sectional dimension of tens to hundreds of nanometres. They may create high porosity mesh networks with significant interconnections among pores, making them suitable for advanced applications. Electrospinning stands out for its ease of use, flexibility, low cost, and variety among the approaches described in the literature. The most common method for making nanofibers is electrospinning. This article extensively describes and summarizes the impact of various process variables on the fabrication of nanofibers. Special attention has been given to scientific and patent prospection to confirm the research interests in nanofibers.

Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation.

Mucoadhesive nanosized crystalline aggregates (NCs) can be delivered by the gastrointestinal, nasal, or pulmonary route to improve retention at particular sites. Itopride hydrochloride (ITH) was selected as a drug candidate due to its absorption from the upper gastrointestinal tract. For drug localization and target-specific actions, mucoadhesive polymers are essential. The current work aimed to use second-generation mucoadhesive polymers (i.e., thiolated polymers) to enhance mucoadhesive characteristics. An ITH-NC formulation was enhanced using response surface methodology. Concentrations of Tween 80 and Polyvinyl pyrrolidone (PVP K-30) were selected as independent variables that could optimize the formulation to obtain the desired entrapment efficacy and particle size/diameter. It was found that a formulation prepared using Tween 80 at a concentration of 2.55% and PVP K-30 at 2% could accomplish the goals for which an optimized formulation was needed. Either xanthan gum (XG) or thiolated xanthan gum (TXG) was added to the optimized formulation to determine how they affected the mucoadhesive properties of the formulation. Studies demonstrated that there was an initial burst release of ITH from the ITH/NC/XG and ITH/NC/TXG in the early hours and then a steady release for 24 h. As anticipated, the TXG formulation had a better mucin interaction, and this was needed to ensure that the drug was distributed to tissues that produce mucus. Finally, at the measured concentrations, the ITH/NC showed minimal cytotoxicity against lung cells, indicating that it may have potential for additional in vivo research. The enhanced bioavailability and mean residence time of the designed mucoadhesive NC formulations were confirmed by pharmacokinetic studies.

A spotlight on application of microwave-assisted modifications of plant derived polymers in designing novel drug delivery systems.

Polymers are a fundamental part of numerous industries and can be conjugated with many other materials and components to have a vast array of products. Biomaterials have been extensively studied for their application in pharmaceutical formulation development, tissue engineering, and biomedical areas. However, the native form of many polymers has limitations concerning microbial contamination, susceptibility, solubility, and stability. Chemical or physical modifications can overcome these limitations by tailoring the properties of polymers to meet several requirements. The polymer modifications are interdisciplinary, cutting across conventional materials, physics, biology, chemistry, medicine, and engineering limitations. Microwave irradiation has become a well-established technique for a few decades to drive and promote chemical modification reactions. This technique allows ease of temperature and power control to perform the synthesis protocols efficiently. Additionally, microwave irradiation contributes to green and sustainable chemistry. In this contribution, microwave-assisted polymer modifications were described with a special focus on their application in developing several novel dosage forms.

A spotlight on alkaloid nanoformulations for the treatment of lung cancer.

Numerous naturally available phytochemicals have potential anti-cancer activities due to their vast structural diversity. Alkaloids have been extensively used in cancer treatment, especially lung cancers, among the plant-based compounds. However, their utilization is limited by their poor solubility, low bioavailability, and inadequacies such as lack of specificity to cancer cells and indiscriminate distribution in the tissues. Incorporating the alkaloids into nanoformulations can overcome the said limitations paving the way for effective delivery of the alkaloids to the site of action in sufficient concentrations, which is crucial in tumor targeting. Our review attempts to assess whether alkaloid nanoformulation can be an effective tool in lung cancer therapy. The mechanism of action of each alkaloid having potential is explored in great detail in the review. In general, Alkaloids suppress oncogenesis by modulating several signaling pathways involved in multiplication, cell cycle, and metastasis, making them significant component of many clinical anti-cancerous agents. The review also explores the future prospects of alkaloid nanoformulation in lung cancer. So, in conclusion, alkaloid based nanoformulation will emerge as a potential gamechanger in treating lung cancer in the near future.

Optimization of process parameters for fabrication of electrospun nanofibers containing neomycin sulfate and Malva sylvestris extract for a better diabetic wound healing.

Diabetes mellitus is one of the most concerning conditions, and its chronic consequences are almost always accompanied by infection, oxidative stress, and inflammation. Reducing excessive reactive oxygen species and the wound's inflammatory response is a necessary treatment during the acute inflammatory phase of diabetic wound healing. Malva sylvestris extract (MS) containing nanofibers containing neomycin sulfate (NS) were synthesized for this investigation, and their impact on the healing process of diabetic wounds was assessed. Using Design Expert, the electrospinning process for the fabrication of NS nanofibers (NS-NF) was adjusted for applied voltage (X1), the distance between the needle's tip and the collector (X2), and the feed rate (X3) for attaining desired entrapment efficacy [EE] and average nanofiber diameter (ND). The optimal formulation can be prepared with 19.11 kV of voltage, 20 cm of distance, and a flow rate of 0.502 mL/h utilizing the desirability approach. All the selected parameters and responses have their impact on drug delivery from nanofibers. In addition, M. sylvestris extracts have been added into the optimal formulation [MS-NS-NF] and assessed for their surface morphology, tensile strength, water absorption potential, and in vitro drug release studies. The NS and MS delivery from MS-NS-NF has been extended for more than 60 h. M. sylvestris-loaded nanofibers demonstrated superior antibacterial activity compared to plain NS nanofibers. The scaffolds featured a broad aspect and a highly linked porous fibrous network structure. Histomorphometry study and the in vitro scratch assay demonstrate the formulation's efficacy in treating diabetic wound healing. The cells treated with MS-NS-NF in vivo demonstrated that wound dressings successfully reduced both acute and chronic inflammations. To improve the healing of diabetic wounds, MS-NS-NF may be regarded as an appropriate candidate for wound dressing.

Compression-coated pulsatile chronomodulated therapeutic system: QbD assisted optimization.

Pulsatile drug delivery systems have drawn attention in contemporary research for designing chronotherapeutic systems. The current work aims to design pulsatile ketorolac tromethamine tablets using compression coating for delayed delivery with a lag time suitable for the treatment of morning stiffness in arthritis. Rapidly disintegrating core tablets of ketorolac tromethamine were formulated using super-disintegrants, and the optimized formulation was compression using PEO WSR coagulant and Eudragit RLPO for delaying the release. The central composite design and response surface methodology were employed to optimize the formulation and process parameters namely PEO WSR Coagulant (X1), Eudragit RLPO (X2), and Hardness (X3). The dependent variables optimized were lag time and time required for 95% drug release. Analysis using response surface graphs and mathematical modeling of the results allowed identifying and quantifying the formulation variables active on the selected responses. A polynomial equation fitted to the data was used to predict the composition with optimum responses. Compression-coated pulsatile tablets' optimized composition exhibited a lag time of 9 h and released 95% of the ketorolac tromethamine in 17.42 h. Validation of the mathematical model assured the reliability of QBD in formulation design. In vivo X-ray imaging and pharmacokinetic studies established a strong relationship between the coated polymers maintaining the desired lag time for delayed delivery of the active to coincide with the chronobiology for enhanced bioavailability at the right time when needed.

Design and Development of Neomycin Sulfate Gel Loaded with Solid Lipid Nanoparticles for Buccal Mucosal Wound Healing.

Drug administration to the wound site is a potential method for wound healing. The drug retention duration should be extended, and drug permeability through the buccal mucosal layer should be regulated. Oral wounds can be caused by inflammation, ulcers, trauma, or pathological lesions; if these wounds are not treated properly, they can lead to pain, infection, and subsequent undesirable scarring. This study aimed to develop Kolliphor-407 P-based gel containing neomycin sulfate (NES) loaded in solid lipid nanoparticles (SLNs) and enhance the antimicrobial activity. By considering lipid concentrations and achieving the lowest particle size (Y1) and maximum entrapment (EE-Y2) effectiveness, the formulation of NES-SLN was optimized using the Box-Behnken design. For the selected responses, 17 runs were formulated (as anticipated by the Design-Expert software) and evaluated accordingly. The optimized formulation could achieve a particle size of 196.25 and EE of 89.27% and was further utilized to prepare the gel formulation. The NES-SLN-G formula was discovered to have a smooth, homogeneous structure and good mechanical and rheological properties. After 24 h of treatment, NES-SLN-G showed a regulated in vitro drug release pattern, excellent ex vivo permeability, and increased in vitro antibacterial activity. These findings indicate the potential application of NES-SLN-loaded gels as a promising formulation for buccal mucosal wound healing.

Augmentation of Antidiabetic Activity of Glibenclamide Microspheres Using S-Protected Okra Powered by QbD: Scintigraphy and In Vivo Studies.

Successful drug delivery by mucoadhesive systems depends on the polymer type, which usually gets adherent on hydration. The intended polymers must sustain the association with biomembranes and preserve or accommodate the drug for an extended time. The majority of hydrophilic polymers tend to make weak interactions like noncovalent bonds, which hampers the positioning of dosage forms at the required target sites, leading to inefficient therapeutic outcomes. It is possible to overcome this by functionalizing the natural polymers with thiol moiety. Further, considering that S-protected thiomers can benefit by improving thiol stability at a broad range of pH and enhancing the residence period at the required target, 2-mercapto-nicotinic acid (MA) was utilized in this present study to shield the free thiol groups on thiolated okra (TO). S-protected TO (STO) was synthesized and characterized for various parameters. Glibenclamide-loaded microspheres were formulated using STO (G-STO-M), and the process was optimized. The optimized formulation has shown complete and controlled release of the loaded drug at the end of the dissolution study. Cell viability assay indicated that the thiolated S-protected polymers gelated very well, and the formulated microspheres were safe. Further, G-STO-M showed considerable in vivo mucoadhesion strength. The glucose tolerance test confirmed the efficacy of STO formulation in minimizing the plasma glucose level. These results favor S-protection as an encouraging tool for improving the absorption of poorly aqueous soluble drugs like glibenclamide.

QbD Supported Optimization of the Alginate-Chitosan Nanoparticles of Simvastatin in Enhancing the Anti-Proliferative Activity against Tongue Carcinoma.

The goal of the current study is to develop a chitosan alginate nanoparticle system encapsulating the model drug, simvastatin (SIM-CA-NP) using a novel polyelectrolytic complexation method. The formulation was optimized using the central composite design by considering the concentrations of chitosan and alginate at five different levels (coded as +1.414, +1, 0, -1, and -1.414) in achieving minimum particle size (PS-Y1) and maximum entrapment efficiency (EE-Y2). A total of 13 runs were formulated (as projected by the Design-Expert software) and evaluated accordingly for the selected responses. On basis of the desirability approach (D = 0.880), a formulation containing 0.258 g of chitosan and 0.353 g of alginate could fulfill the prerequisites of optimum formulation in achieving 142.56 nm of PS and 75.18% EE. Optimized formulation (O-SIM-CAN) was further evaluated for PS and EE to compare with the theoretical results, and relative error was found to be within the acceptable limits, thus confirming the accuracy of the selected design. SIM release from O-SIM-CAN was retarded significantly even beyond 96 h, due to the encapsulation in chitosan alginate carriers. The cell viability study and Caspase-3 enzyme assay showed a notable difference in contrast to that of plain SIM and control group. All these stated results confirm that the alginate-chitosan nanoparticulate system enhanced the anti-proliferative activity of SIM.

An updated review on potential therapeutic drug candidates, vaccines and an insight on patents filed for COVID-19.

The outbreak of COVID-19 was recognized in December 2019 in China and as of October5th, the pandemic was swept through 216 countries and infected around 34,824,108 individuals, thus posing an unprecedented threat to world's health and economy. Several researchers reported that, a significant mutation in membrane proteins and receptor binding sites of preceding severe acute respiratory syndrome coronavirus (SARS-CoV) to turned as novel SARS-CoV-2 virus and disease was named as COVID-19 (Coronavirus disease 2019). Unfortunately, there is no specific treatment available for COVID-19 patients. The lessons learned from the past management of SARS-CoV and other pandemics, have provided some insights to treat COVID-19. Currently, therapies like anti-viral treatment, immunomodulatory agents, plasma transfusion and supportive intervention etc., are using to treat the COVID-19. Few of these were proven to provide significant therapeutic benefits in treating the COVID-19, however no drug is approved by the regulatory agencies. As the fatality rate is high in patients with comorbid conditions, we have also enlightened the current in-line treatment therapies and specific treatment strategies in comorbid conditions to combat the emergence of COVID-19. In addition, pharmaceutical, biological companies and research institutions across the globe have begun to develop thesafe and effective vaccine for COVID-19. Globally around 170 teams of researchers are racing to develop the COVID-19 vaccine and here we have discussed about their current status of development. Furthermore, recent patents filed in association with COVID-19 was elaborated. This can help many individuals, researchers or health workers, in applying these principles for diagnosis/prevention/management/treatment of the current pandemic.

Preparation, Optimization and Evaluation of Chitosan-Based Avanafil Nanocomplex Utilizing Antioxidants for Enhanced Neuroprotective Effect on PC12 Cells.

(1) Introduction: in recent decades, interdisciplinary research on the utilization of natural products as "active moiety carriers" was focused on due to their superior safety profile, biodegradability, biocompatibility and the ability for sustained or controlled release activity. The nano-based neuroprotective strategy is explored as an imperative treatment for diabetic neuropathy (DN). Avanafil (AV), that selectively inhibits the degradation of cGMP-specific phosphodiesterase, thereby increasing the levels of cGMP, makes a decisive mediator for cytoprotection. (2) Methods: AVnanocomplex formulations were prepared by a modified anti-solvent precipitation method and the method was optimized by Box-Behnken design. An optimized formulation was characterized and evaluated for various in vitro parameters; (3) results:based on the desirability approach, the formulation containing 2.176 g of chitosan, 7.984 g of zein and 90% v/v ethanol concentration can fulfill the prerequisites of optimum formulation (OB-AV-NC).OB-AV-NC was characterized and evaluated for various parameters. The neuroprotective mechanism of AV was evaluated by pretreatment of PC12 cells with plain AV, avanafil nanocomplex (NC) without antioxidants (AV-NC) and with antioxidants (α-Lipoic acid LP; Ellagic Acid EA), AV-LP-EA-Nanocomplex has also shown considerable attenuation in intracellular reactive oxygen species (ROS) and lipid peroxidation with a significant increase in the PC 12 viability under HG conditions in comparison to pure AV; (4) conclusion: the nanocomplex of AV prepared to utilize natural polymers and antioxidants aided for high solubility of AV and exhibited desired neuroprotective activity.This can be one of the promisingstrategy to translate the AV nanocomplex with safety and efficacy in treating DN.

Wireless Networking-Driven Healthcare Approaches in Combating COVID-19.

Since its outbreak, the coronavirus (COVID-19) pandemic has caused havoc on people's lives. All activities were paused due to the virus's spread across the continents. Researchers have been working hard to find new medication treatments for the COVID-19 pandemic. The World Health Organization (WHO) recommends that safety and self-measures play a major role in preventing the virus from spreading from one person to another. Wireless technology is playing a critical role in avoiding viral propagation. This technology mainly comprises of portable devices that assist self-isolated patients in adhering to safe precautionary measures. Government officials are currently using wireless technologies to identify infected people at large gatherings. In this research, we gave an overview of wireless technologies that assisted the general public and healthcare professionals in maintaining effective healthcare services during COVID-19. We also discussed the possible challenges faced by them for effective implementation in day-to-day life. In conclusion, wireless technologies are one of the best techniques in today's age to effectively combat the pandemic.

In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma.

The goal of this study is to develop optimized chitosan-coated Simvastatin (SIM) nanoparticles (NPs) loaded in an in situ gel (ISG) formulation via a face-centered central composite design (FCCCD). Coated SIM-NPs were doped with Quercetin (QRC) using a modified nanoprecipitation method. The concentrations of poloxamer 188 (A) and chitosan (B) at five different levels, plus/minus alpha (+1.414 and -1.414: axial points), plus/minus 1 (factorial points) and the center point were optimized for particle size (PS-Y1), entrapment efficacy (EE-Y2) and stability index (SI-Y3). Based on the desirability approach, a formulation containing poloxamer 188 0.24% and chitosan 0.43% renders the prerequisites of optimum formulation for preparing SIM-QRC NP-loaded ISG. Scanning microscopy showed spherical SIM-NPs, indicating monodispersity in the range of 0.50 ± 0.04 nm with a charge of +32.42 mV. The optimized formulation indicated the highest EE 79.67% and better stability at 4 °C. Drug release from SIM-QRC NP-loaded ISG was slower to plateau by up to 96 h and, at the end of 168 h, only 65.12% of SIM was released in a more controlled manner in comparison to SIM-QRC NPs and plain SIM. ISG formulation showed a considerable increase in apoptosis occurrence through caspase-3 mediation and it also enhanced the tumor suppressor protein levels. Enhanced biological activity of SIM was observed due to QRC enabling promising drug and polymer synergistic interaction. The proposed formulation can provide a breakthrough in localized therapy, overcoming the potential drawbacks of systemic chemotherapy for tongue carcinoma.