Extraction, Characterization and Pharmacological Evaluation of Aegle marmelos Leaves

In the present day, antibiotic drugs are gradually becoming obsolete due to the development of antimicrobial resistance. As a result, the scientific community is in search of new antibiotic drugs which can be safely administered to the patents. Natural products are generally known for their nontoxic nature and many of them are known to produce a variety of pharmacological activities. The aim of this work is to extract the leaves of Aegle marmelos, phytochemical characterization of the extract, identification of phytoconstituents by thin layer chromatography, ATR-FTIR Spectroscopy of extract and evaluation of its antimicrobial activity. Extraction of the leaves of Aegle marmelos has been conducted using a Soxhlet apparatus. About 10.32% yield of extract was obtained. Phytochemical screening of the ethanolic leaf extract by standard methods showed the presence of secondary metabolites such as alkaloids, carbohydrates, phenolic compounds, flavonoids, saponins and triterpenoids which were confirmed by TLC. ATR-FTIR Spectroscopic study was conducted to determine the type of functional groups present in extract. The ethanolic leaf extract also produced antibacterial activity against gram positive bacteria Staphylococcus aureus and gram-negative bacteria Escherichia coli and zone of inhibition was 14 mm and 16 mm respectively when compared to standard antibiotic tetracycline. From this research it can be inferred that ethanolic leaf extract of Aegle marmelos has antimicrobial activity because of the presence of secondary metabolites in it. Further investigation will hereby be conducted in future regarding the route of administration of the extract and the type of dosage form. &nbsp

State-of-the-art preclinical evaluation of COVID-19 vaccine candidates

Peer reviewedPublisher PD

A Universal Nanogel-Based Coating Approach for Medical Implant Materials

Coatings are essential for biomedical applications antifouling and antimicrobialproperties, supporting cell adhesion and tissue integration and particularlyinteresting in this field are nanogel (nGel)-based coatings. Since biomaterialsdiffer in physiochemical properties, specific nGel-coating strategies need to bedeveloped for every distinct material, leading to complex coating strategies.Hence, the solution lies in adopting a universal strategy to apply the same nGelcoating with the same function on a wide range of implant surfaces. To this end, auniversal nGel-based coating approach provides the same coating using a singlemethod on implant materials including stiff polymer materials, metals, ceramics,glass, and elastomers. The coating formation is achieved by electrostatic interactionsbetween oxygen plasma–activated surfaces and positively charged nGelsusing a spray-deposition method. Fluorescent labels are introduced into thenGels as a model for post-modification capabilities to increase the functionality ofthe coating. The coating is highly stable under in vitro physiological conditionswith the retention of its function on different clinically relevant materials.Meanwhile, the in vivo study indicates that the nGel coating on a polyvinylidenefluoride hernia mesh is stable and biocompatible, therefore, making the coatingand the coating strategy, a highly impactful approach for future clinicaldevelopments

Effects of sterilization on nanogel-based universal coatings:An essential step for clinical translation

Implant associated infections are a serious threat to the well-being of patients, which can be mitigated by taking effective disinfection/sterilization (D/S) methods into account. Nanogels (nGel) are stimuli sensitive polymeric hydrogel particles, which have provided numerous innovative applications in the biomedical field to enhance antifouling, antibacterial properties, or drug delivery, or they can be employed as imaging modalities or can be applied as a coating on biomaterials (implants). Prior to translating their application towards clinical use, nGel-based coated implant materials must undergo an intermediary, pre-requisite process of cleaning, disinfection, and sterilization, in sequence. The interplay among the three crucial pillars- the implant material, the nGel coating (with specific function), and the applied D/S processes influence the fate (success or failure) of medical implant in the host body. In this study, we investigated a previously developed NIPAM-co-APMA core shell nGel coating on various clinically-relevant polymeric and inorganic implant materials and tested them on a diverse range of D/S techniques to assess the retention of the coating quality and antifouling function. The stability and integrity of the nGel coating was analyzed by performing Atomic Force Microscopy and the retention of the antifouling function of the nGel-coating after sterilization was studied by Colony forming units against S. aureus RN4220. Among all the materials that were coated, polymeric materials- polypropylene and polyetheretherketone exhibited exceptional coating stability, post-sterilization while also demonstrating a considerable reduction in bacterial attachment with respect to their ‘uncoated, sterilized’ and ‘coated, non-sterilized’ controls. Although often overlooked, sterilization is an indispensable part of clinical translation, therefore research in this domain is of utmost importance when considering clinical translatability.</p

Effects of sterilization on nanogel-based universal coatings: An essential step for clinical translation

Implant associated infections are a serious threat to the well-being of patients, which can be mitigated by taking effective disinfection/sterilization (D/S) methods into account. Nanogels (nGel) are stimuli sensitive polymeric hydrogel particles, which have provided numerous innovative applications in the biomedical field to enhance antifouling, antibacterial properties, or drug delivery, or they can be employed as imaging modalities or can be applied as a coating on biomaterials (implants). Prior to translating their application towards clinical use, nGel-based coated implant materials must undergo an intermediary, pre-requisite process of cleaning, disinfection, and sterilization, in sequence. The interplay among the three crucial pillars- the implant material, the nGel coating (with specific function), and the applied D/S processes influence the fate (success or failure) of medical implant in the host body. In this study, we investigated a previously developed NIPAM-co-APMA core shell nGel coating on various clinically-relevant polymeric and inorganic implant materials and tested them on a diverse range of D/S techniques to assess the retention of the coating quality and antifouling function. The stability and integrity of the nGel coating was analyzed by performing Atomic Force Microscopy and the retention of the antifouling function of the nGel-coating after sterilization was studied by Colony forming units against S. aureus RN4220. Among all the materials that were coated, polymeric materials- polypropylene and polyetheretherketone exhibited exceptional coating stability, post-sterilization while also demonstrating a considerable reduction in bacterial attachment with respect to their ‘uncoated, sterilized’ and ‘coated, non-sterilized’ controls. Although often overlooked, sterilization is an indispensable part of clinical translation, therefore research in this domain is of utmost importance when considering clinical translatability

Discrimination of Ligands with Different Flexibilities Resulting from the Plasticity of the Binding Site in Tubulin

Tubulin, an α,β heterodimer, has four distinct ligand binding sites (for paclitaxel, peloruside/laulimalide, vinca, and colchicine). The site where colchicine binds is a promising drug target for arresting cell division and has been observed to accommodate compounds that are structurally diverse but possess comparable affinity. This investigation, using two such structurally different ligands as probes (one being colchicine itself and another, TN16), aims to provide insight into the origin of this diverse acceptability to provide a better perspective for the design of novel therapeutic molecules. Thermodynamic measurements reveal interesting interplay between entropy and enthalpy. Although both these parameters are favourable for TN16 binding (Δ<i>H</i> < 0, Δ<i>S</i> > 0), but the magnitude of entropy has the determining role for colchicine binding as its enthalpic component is destabilizing (Δ<i>H</i> > 0, Δ<i>S</i> > 0). Molecular dynamics simulation provides atomistic insight into the mechanism, pointing to the inherent flexibility of the binding pocket that can drastically change its shape depending on the ligand that it accepts. Simulation shows that in the complexed states both the ligands have freedom to move within the binding pocket; colchicine can switch its interactions like a “flying trapeze”, whereas TN16 rocks like a “swing cradle”, both benefiting entropically, although in two different ways. Additionally, the experimental results with respect to the role of solvation entropy correlate well with the computed difference in the hydration: water molecules associated with the ligands are released upon complexation. The complementary role of van der Waals packing versus flexibility controls the entropy–enthalpy modulations. This analysis provides lessons for the design of new ligands that should balance between the “better fit” and “flexibility”’, instead of focusing only on the receptor–ligand interactions

Discrimination of Ligands with Different Flexibilities Resulting from the Plasticity of the Binding Site in Tubulin

Tubulin, an α,β heterodimer, has four distinct ligand binding sites (for paclitaxel, peloruside/laulimalide, vinca, and colchicine). The site where colchicine binds is a promising drug target for arresting cell division and has been observed to accommodate compounds that are structurally diverse but possess comparable affinity. This investigation, using two such structurally different ligands as probes (one being colchicine itself and another, TN16), aims to provide insight into the origin of this diverse acceptability to provide a better perspective for the design of novel therapeutic molecules. Thermodynamic measurements reveal interesting interplay between entropy and enthalpy. Although both these parameters are favourable for TN16 binding (Δ<i>H</i> < 0, Δ<i>S</i> > 0), but the magnitude of entropy has the determining role for colchicine binding as its enthalpic component is destabilizing (Δ<i>H</i> > 0, Δ<i>S</i> > 0). Molecular dynamics simulation provides atomistic insight into the mechanism, pointing to the inherent flexibility of the binding pocket that can drastically change its shape depending on the ligand that it accepts. Simulation shows that in the complexed states both the ligands have freedom to move within the binding pocket; colchicine can switch its interactions like a “flying trapeze”, whereas TN16 rocks like a “swing cradle”, both benefiting entropically, although in two different ways. Additionally, the experimental results with respect to the role of solvation entropy correlate well with the computed difference in the hydration: water molecules associated with the ligands are released upon complexation. The complementary role of van der Waals packing versus flexibility controls the entropy–enthalpy modulations. This analysis provides lessons for the design of new ligands that should balance between the “better fit” and “flexibility”’, instead of focusing only on the receptor–ligand interactions

Discrimination of Ligands with Different Flexibilities Resulting from the Plasticity of the Binding Site in Tubulin

Tubulin, an α,β heterodimer, has four distinct ligand binding sites (for paclitaxel, peloruside/laulimalide, vinca, and colchicine). The site where colchicine binds is a promising drug target for arresting cell division and has been observed to accommodate compounds that are structurally diverse but possess comparable affinity. This investigation, using two such structurally different ligands as probes (one being colchicine itself and another, TN16), aims to provide insight into the origin of this diverse acceptability to provide a better perspective for the design of novel therapeutic molecules. Thermodynamic measurements reveal interesting interplay between entropy and enthalpy. Although both these parameters are favourable for TN16 binding (Δ<i>H</i> < 0, Δ<i>S</i> > 0), but the magnitude of entropy has the determining role for colchicine binding as its enthalpic component is destabilizing (Δ<i>H</i> > 0, Δ<i>S</i> > 0). Molecular dynamics simulation provides atomistic insight into the mechanism, pointing to the inherent flexibility of the binding pocket that can drastically change its shape depending on the ligand that it accepts. Simulation shows that in the complexed states both the ligands have freedom to move within the binding pocket; colchicine can switch its interactions like a “flying trapeze”, whereas TN16 rocks like a “swing cradle”, both benefiting entropically, although in two different ways. Additionally, the experimental results with respect to the role of solvation entropy correlate well with the computed difference in the hydration: water molecules associated with the ligands are released upon complexation. The complementary role of van der Waals packing versus flexibility controls the entropy–enthalpy modulations. This analysis provides lessons for the design of new ligands that should balance between the “better fit” and “flexibility”’, instead of focusing only on the receptor–ligand interactions