ENHANCED ORAL BIOAVAILABILITY OF TENOFOVIR FROM IONOTROPICALLY GELLED MICROBEADS

Objective: The main objective of the present investigation was to develop microbeads of tenofovir. Tenofovir, a BCS class III drug has a poor bioavailability of 25%, and it is administered 300 mg once a day. By incorporating the drug into a microparticulate carrier, it is expected that the dissolution profile and the oral bioavailability may be increased. Methods: Reinforced gellan-chitosan and calcium chloride beads of tenofovir were prepared by ionotropic gelation method employing various different concentrations of gellan, chitosan, calcium chloride and tenofovir. The beads were evaluated for various physico-chemical parameters such as particle size determination, drug entrapment efficiency, swelling studies, infra red spectroscopy study, differential scanning calorimetry, x-ray diffraction analysis, scanning electron microscopy, in vitro drug release study, cytotoxicity study and in vivo oral bioavailability studies. Results: From the results, it can be concluded that the formulation TB-III exhibited higher drug entrapment efficiency (46.09±0.21), a higher swelling index, sustained drug release for a period of 24 h. The pharmacokinetic profile of the drug from microbeads exhibited an increased oral bioavailability (1.25 times higher than that of pure drug), decreased elimination rate (1.32 times lesser for drug in microbeads) with prolonged elimination half-life (1.32 times higher than pure tenofovir). Conclusion: Tenofovir loaded microbeads demonstrated as a better delivery system for the modified release of drug and also to navigate the drawbacks associated with the conventional therapy

SUSTAINED RELEASE MICROBEADS OF RITONAVIR: IN VITRO AND IN VIVO EVALUATION

Objective: The main aim of the present investigation was to develop sustained release microbeads of ritonavir that has a shorter half-life (3-5 h) and requires twice a day administration. These formulations exhibit a sustained release of ritonavir that would expect to improve the therapy, better drug utilization, and patient compliance. Methods: Gellan-chitosan and calcium chloride reinforced beads of ritonavir were prepared by ionotropic gelation method employing different concentrations of gellan, chitosan, calcium chloride and drug. The prepared beads were evaluated for various physicochemical parameters such as particle size determination, drug entrapment efficiency, swelling studies, infrared spectroscopy study, differential scanning calorimetry, x-ray diffraction analysis, scanning electron microscopy, in vitro drug release study and in vivo bioavailability studies. Results: From the results, formulation GC-II exhibited higher drug entrapment efficiency (79.65±0.012), higher swelling index, sustained drug release over a period of 24 h, increased oral bioavailability (2.07 times higher than that of pure drug) and decreased elimination rate (2.15 times lesser for ritonavir microbeads) with prolonged elimination half-life (2.15 times more than pure drug) as compared to pure drug. Conclusion: Ritonavir microbeads have demonstrated as a better delivery system for the sustained release of the drug; which may in turn circumvent the drawbacks associated with the conventional therapy

A REVIEW ON GREEN-SYNTHESIS OF CERIUM OXIDE NANOPARTICLES: FOCUS ON CENTRAL NERVOUS SYSTEM DISORDERS

Green Synthesized Cerium oxide nanoparticles (CeO2NPs) have sparked a lot of interest in numerous disciplines of science and Technology during the past decade. A wide range of biological resources has been employed in synthesizing CeO2NPs, including plants, microorganisms, and other biological products. Biosynthesis procedures, current knowledge, and prospects in the synthesis of Green synthesis of CeO2NPs are also discussed. Neurodegenerative diseases, such as aging, trauma, Alzheimer's and Parkinson's, and other neurological problems, are linked to higher oxidative stress and superoxide radicals generation. Cerium oxide nanoparticles' antioxidant properties suggest that they may be useful in the treatment of CNS diseases. The biological antioxidant benefits of cerium oxide nanoparticles on extending cell and organism lifespan, preventing a free radical attack, and preventing trauma-induced neurological damage are discussed in this section. CeO2NPs, an aspect of nanotechnology, would emerge as a novel drug delivery carrier through therapeutic strategies. In several diseases oxidative stress and inflammation. CeO2NPs exhibited a remarkable ability to switch between+3 and+4 oxidation states making this an efficient therapeutic option and an effective drug delivery agent. Further Reactive oxygen and nitrogen species. The overall goal of this study is to provide reasonable insight into CeO2NPs as new therapeutic agents and to solve the challenges, of safely and effectively employing these CeO2NPs for efficient management of Central Nervous System diseases

Optimizing nitrogen and potassium for aerobic rice (Oryza sativa L.) in elevated -temperature environments

Increasing atmospheric temperature is the consequence of global warming, which is anticipated to impact crop growth and development and decrease the productivity of crops in tropical regions. The field experiments were conducted during the summer season of 2020 and 2021 at College farm, Kerala Agricultural University, Thrissur, to study the response of different rice varieties to elevated temperatures (2-3°C above ambient condition) during the flowering stage with different N and K levels under aerobic conditions. The experiments were laid out in Randomized Block Design consisting of eight treatments viz. V1F0 – Vaishak + 60 kg N and 30 kg K2O (Control – ambient temperature); V1F1- Vaishak+60 kg N and 30 kg K2O; V1F2- Vaishak+90 kg N and 45 kg K2O; V1F3- Vaishak+120 kg N and 60 kg K2O (under stress); V2F0- Aiswarya+60 kg N and 30 kg K2O (Control – No stress);V2F1- Aiswarya+60 kg N and 30 kg K2O; V2F2- Aiswarya+90 kg N and 45 kg K2O; V2F3- Aiswarya+120 kg N and 60 kg K2O (under stress). The tallest plant, higher number of tillers per hill, leaf area index, grain protein, grain and straw yield were observed with higher N and K levels (120: 60 kg/ha). The study revealed that the application of 90 kg N and 45 kg K2O produced comparable grain yields of Vaishak (2365 kg/ha in 2020 and 2186 kg/ha in 2021) and Aiswarya (2395 kg/ha in 2020 and 2104 kg/ha in 2021) to that of 120 kg N and 60 kg K2O/ha in both Vaishak and Aiswarya. Under elevated temperatures, the variety Aiswarya and Vaishak gave better yields to the farmers when supplied with 90 kg N and 45 kg K2O.  

ANTIOXIDANT AND ANTI-PROLIFERATIVE EFFECTS OF AN ETHYL ACETATE FRACTION OF THE HYDRO-ETHANOLIC EXTRACT OF SYNEDRELLA NODIFLORA (L) GAERTN

Objective: Synedrella nodiflora is traditionally used in the treatment of several ailments. Pharmacologically, this plant has anticonvulsant, sedative, anti-nociceptive and anti-proliferative effects. This study further investigated S. nodiflora for its antioxidant and in vitro inhibition of cancerous cell lines. Methods: Phytochemical assays, and the DPPH radical scavenging method were employed in preliminary screening for antioxidant activities of the crude hydro-ethanolic extract (SNE) and resulting fractions. The potent ethyl acetate fraction (EAF), was further investigated for total phenol and flavonoid contents, reducing power, lipid peroxidation potential, and cytotoxic effects on human breast cancer (MCF-7), leukemic (Jurkat), and normal liver (Chang’s liver) cell lines. Results: The extract contained phenols, flavonoids, tannins, glycosides, sterols, terpenoids, and alkaloids. It scavenged for DPPH with an IC50 of 114 µg/ml, whereas that of EAF was 8.9 µg/ml. EAF prevented peroxidation of egg lecithin at an IC50 of 24.01±0.08 µg/ml. These IC50s are four and three times lower than the reference standards. EAF produced anti-proliferative effects against MCF-7, and Jurkat cell lines with IC50s of 205.2 and 170.9 µg/ml, respectively. EAF had a high IC50 of 252.2 µg/ml against Chang’s liver cells. At 0.1 mg/ml EAF had similar total flavonoid content to SNE, but a significantly higher total phenol content. Conclusion: The ethyl acetate fraction of S. nodiflora, exhibited the most potent antioxidant activity. It inhibited the proliferation of breast and leukemic cancer cell lines, whiles having weak cytotoxic effect on normal liver cells. These can be explored for further drug development

MOLECULAR DOCKING INSIGHTS INTO PROBIOTICS AS POTENTIAL INHIBITORS OF THE PI3K PATHWAY FOR COLON CANCER THERAPY

Objective: This study investigates the interactions of probiotics-derived bacteriocins with Phosphoinositide 3-kinases (PI3Ks), a key enzyme involved in cell growth and survival pathways, with a focus on the cancer-associated PI3K pathway (PDB ID: 1E8X). The aim is to explore the anti-cancer potential of these bacteriocins as inhibitors of the PI3K catalytic subunit. Methods: Using the Glide module, the study first involved molecular docking of bacteriocins. Next, an Absorption, Distribution, Metabolism, and Excretion (ADME) study was conducted using Qikprop. The Prime Molecular Mechanics Generalised Born Surface Area (MM-GBSA) method was used to calculate binding free energy. Results: Five bacteriocins demonstrated significant binding affinity and interactions, including hydrogen and hydrophobic bonds, with key residues such as Tyr867, Trp812, Asp950, Asn951, Lys802, Lys890, Lys833, Val882, Ser806, Thr886, and Gln893 in the PI3K catalytic subunit (PDB ID: 1E8X). Among these, Plantaricin D exhibited an excellent XP-docking score of -7.47 kcal/mol, indicating strong binding potential. Prime MM-GBSA analysis revealed promising binding affinities with ΔBind (-92.85 kcal/mol), ΔLipo (-65.81 kcal/mol), and ΔVdW (-47.34 kcal/mol). The ligand consistently interacted with residues Asp950, Lys890, Gln893, Ser894, Thr887, Ala885, Tyr757, Asp758, Lys802, and Val759. Conclusion: Plantaricin D bacteriocin, characterized by functional groups including the primary amine (NH₂), carbonyl (C=O), hydroxide (OH), and oxygen (O), demonstrates significant potential as a PI3K inhibitor. This suggests its promising application as an anti-cancer agent, particularly for colon cance

MOLECULAR DOCKING INSIGHTS INTO PROBIOTICS SAKACIN P AND SAKACIN A AS POTENTIAL INHIBITORS OF THE COX-2 PATHWAY FOR COLON CANCER THERAPY

Objective: This study aims to explore the interactions between probiotics-derived bacteriocins and the COX (cyclooxygenase) pathway, particularly focusing on the cancer-associated COX-2 (cyclooxygenase-2) enzyme (PDB ID: 6COX). The goal is to assess the potential of these bacteriocins as inhibitors of COX-2, investigating their possible anti-cancer effects through modulation of this key enzyme involved in cell growth and survival pathways. Methods: Using the Glide module, the study first involved the molecular docking of bacteriocins. Next, an Absorption, Distribution, Metabolism, and Excretion (ADME) study was conducted using Qikprop. The Prime Molecular Mechanics Generalised Born Surface Area (MM-GBSA) method was used to calculate binding free energy. Results: Four bacteriocins demonstrated significant binding affinity and interactions, including hydrogen and hydrophobic bonds, with key residues such as Tyr385, Ser530, Tyr355, Arg120, Phe518, and Leu352, in the associated COX-2 enzyme(PDB ID: 6COX). Among these, Sakacin P exhibited an excellent XP-docking score of -6.73 kcal/mol, indicating strong binding potential. Prime MM-GBSA analysis revealed promising binding affinities with ΔBind (-90.85 kcal/mol), ΔLipo (-64.81 kcal/mol), and ΔVdW (-46.34 kcal/mol). The ligand consistently interacted with residues Tyr355, and Arg120. Conclusion: Sakacin P bacteriocin, characterized by functional groups including the primary amine (NH₂), and oxygen (O), demonstrates significant potential as a COX-2 enzyme inhibitor. This suggests its promising application as an anti-cancer agent, particularly for colon cancer

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New <i>Serratia marcescens</i> JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of <i>Serratia</i> Species for Biological Applications

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography–mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound’s structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 μg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets