The escalating global challenge of antimicrobial resistance demands innovative approaches. This review delves into the current status and future prospects of bioengineered metallic nanoparticles derived from natural sources as potent antimicrobial agents. The unique attributes of metallic nanoparticles and the abundance of natural resources have sparked a burgeoning field of research in combating microbial infections. A systematic review of the literature was conducted, encompassing a wide range of studies investigating the synthesis, characterization, and antimicrobial mechanisms of bioengineered metallic nanoparticles. Databases such as PubMed, Scopus, Web of Science, ScienceDirect, Springer, Taylor & Francis online and OpenAthen were extensively searched to compile a comprehensive overview of the topic. The synthesis methods, including green and sustainable approaches, were examined, as were the diverse biological sources used in nanoparticle fabrication. The amalgamation of metallic nanoparticles and natural products has yielded promising antimicrobial agents. Their multifaceted mechanisms, including membrane disruption, oxidative stress induction, and enzyme inhibition, render them effective against various pathogens, including drug-resistant strains. Moreover, the potential for targeted drug delivery systems using these nanoparticles has opened new avenues for personalized medicine. Bioengineered metallic nanoparticles derived from natural sources represent a dynamic frontier in the battle against microbial infections. The current status of research underscores their remarkable antimicrobial efficacy and multifaceted mechanisms of action. Future prospects are bright, with opportunities for scalability and cost-effectiveness through sustainable synthesis methods. However, addressing toxicity, regulatory hurdles, and environmental considerations remains crucial. In conclusion, this review highlights the evolving landscape of bioengineered metallic nanoparticles, offering valuable insights into their current status and their potential to revolutionize antimicrobial therapy in the future. Graphical Abstract

Aim: The current paper was an attempt to design a sustained release dosage form using various grades of hydrophilic polymers, Hypromellose (hydroxyl-propyl methylcellulose [HPMC] K15M, HPMC K100M and HPMC K200M) and Polyacrylate polymers, Eudragit RL100 and Eudragit RS100 with or without incorporating ethyl cellulose on a matrix-controlled drug delivery system of Metformin hydrochloride. Materials and Methods: Laboratory scale batches of nine tablet formulations were prepared by wet granulation technique (Low shear). Micromeritic properties of the granules were evaluated prior to compression. Tablets were characterized as crushing strength, friability, weight variation, thickness, drug content or assay and evaluated for in-vitro release pattern for 12 h using Phosphate buffer of pH 6.8 at 37 ± 0.5°C. The in-vitro release mechanism was evaluated by kinetic modeling. Results and Discussion: The results obtained revealed that HPMC K200M at a concentration of 26% in formulation (F6) was able to sustain the drug release for 12 h and followed the Higuchi pattern quasi-Fickian diffusion. With that, combined effect of HPMC K15M as an extragranular section and Eudragit RS100 displayed a significant role in drug release. Dissolution data were compared with innovator for similarity factor (f2), and exhibited an acceptable value of ≥50 Three production validation scale batches were designed based on lab scale best batch and charged for stability testing, parameters were within the limit of acceptance. There was no chemical interaction found between the drug and excipients during Fourier Transform Infrared Spectroscopy (FTIR) and Differential scanning calorimetry study. Conclusion: Hence, combinely HPMC K200M and Eudragit RS100 at a suitable concentration can effectively be used to sustain drug release.

Liver disorders like hepatitis, cirrhosis, and hepatocellular carcinoma present a significant global health challenge, with high morbidity and mortality rates. Key factors contributing to liver disorders include inflammation, oxidative stress, and apoptosis. Due to their multifaceted action, natural compounds are promising candidates for mitigating liver-related disorders. Research studies revealed the antioxidant, anti-inflammatory, and detoxifying properties of natural compounds like curcumin, glycyrrhizin, and silymarin and their potential for liver detoxification and protection. With advancements in nanotechnology in drug delivery, natural compounds have improved stability and targetability, thereby enhancing their bioavailability and therapeutic efficiency. Further, recent advancements in genomics and an increased understanding of genetic factors influencing liver disorders and the hepatoprotective effects of natural agents made way for personalized medicine. Moreover, combinatorial therapy with natural products, synthetic drugs, or other natural agents has improved therapeutic outcomes. Even though clinical trials have confirmed the efficiency of natural compounds as hepatoprotective agents, several challenges remain unanswered in their translation to clinical practice. Therefore, it is logical to integrate natural compounds with nanotechnology and genomics to further advance hepatoprotection. This review gives an overview of the substantial progress made in the field of hepatoprotection, with specific emphasis on natural compounds and their integration with nanotechnology and genomics. This provides valuable insights for future research and innovations in developing therapeutic strategies for liver disorders.

Background: Drug metabolism is a complex mechanism of human body systems to detoxify foreign particles, chemicals, and drugs through bio alterations. It involves many biochemical reactions carried out by invivo enzyme systems present in the liver, kidney, intestine, lungs, and plasma. After drug administration, it crosses several biological membranes to reach into the target site for binding and produces the therapeutic response. After that, it may undergo detoxification and excretion to get rid of the biological systems. Most of the drugs and its metabolites are excreted through kidney via urination. Some drugs and their metabolites enter into intestinal mucosa and excrete through feces. Few of the drugs enter into hepatic circulation where they go into the intestinal tract. The drug leaves the liver via the bile duct and is excreted through feces. Therefore, the study of total methodology of drug biotransformation and interactions with various targets is costly.Methods: To minimize time and cost, in-silico algorithms have been utilized for lead-like drug discovery. Insilico modeling is the process where a computer model with a suitable algorithm is developed to perform a controlled experiment. It involves the combination of both in-vivo and in-vitro experimentation with virtual trials, eliminating the non-significant variables from a large number of variable parameters. Whereas, the major challenge for the experimenter is the selection and validation of the preferred model, as well as precise simulation in real physiological status.Results: The present review discussed the application of in-silico models to predict absorption, distribution, metabolism, and excretion (ADME) properties of drug molecules and also access the net rate of metabolism of a compound.Conclusion: : It helps with the identification of enzyme isoforms; which are likely to metabolize a compound, as well as the concentration dependence of metabolism and the identification of expected metabolites. In terms of drug-drug interactions (DDIs), models have been described for the inhibition of metabolism of one compound by another, and for the compound–dependent induction of drug-metabolizing enzymes.

Objective: The present investigation aimed to prepare metronidazole (MTZ) topical bigel for the effective delivery of MTZ and to study the effect of used variables as per statistical design. The study also signifies the implementation of the statistical method using the Quality by Design technique for MTZ bigel. Methods: The MTZ bigels were prepared as per the runs suggested by Box Behnken design (BBD) using statistical software. A total of 28 runs were suggested by the BBD, considering sodium carboxymethylcellulose (Na CMC), guar gum, hydrogel and RPM as independent variables. The prepared bigels were evaluated for organoleptic properties, percentage drug content, spreadability, viscosity, percentage in-vitro drug release, and antimicrobial efficacy. Model selectivity was ascertained by p-value considering responses along with predicted R² and adjusted R² values.The fitting of model was ascertained by F-value as well as “lack of fit” was carried out to find out the suitability of the experimental design. Furthermore, the characteristic distribution of data was ascertained by the “normal plot of residual” method. The compatibility of MTZ and excipients in bigels was confirmed by FTIR and the crystalline nature of MTZ in formulations was studied by DSC and XRD studies. Furthermore, the dispersion of bigel was assessed by the SEM study. Results: The effect of independent variables on spreadability (mm), viscosity (cp), pH, drug release in 6 hours (%)and drug content (%) was evaluated. The optimized formulation was selected and evaluated by a polynomial equation while considering the p-value. These variables showed a significant effect on responses. A less significant difference was observed (6.37, 14463, 6.97, 86.29, and 67.47, respectively, for spreadability, viscosity, pH, and percentage drug release and % drug content) between the observed and predicted values indicating the model’s suitability. The prepared bigels were found to be compatible and globules uniformly dispersed throughout the bigel. Conclusion: The 3D response surface design ascertained the optimal MTZ bigel at 1.25g of NaCMC, 0.5g of guargum, 37.5g hydrogel, and 1000 RPM. The selected bigel showed good antimicrobial efficacy against S. Aureus and may be considered an effective delivery vehicle for MTZ.