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Generally, protein-based vaccines are available in liquid form and are highly susceptible to instability under elevated temperature changes including freezing conditions. There is a need to create a convenient formulation of protein/peptides that can be stored at ambient conditions without loss of activity or production of adverse effects. The efficiency of naturally occurring biocompatible polymer dextran in improving the shelf-life and biological activity of a highly thermally unstable plague vaccine candidate protein called Low Calcium Response V antigen (LcrV), which can be stored at room temperature (30 ± 2 °C), has been evaluated. To determine the preferential interactions with molecular-level insight into solvent–protein interactions, analytical techniques such asspectroscopy, particle size distribution, gel electrophoresis, microscopy, and thermal analysis have been performed along with the evaluation of humoral immune response, invivo. The analytical methods demonstrate the structural stability of the LcrV protein by expressing its interaction with the excipients in the formulation. The invivo studies elicited the biological activity of the formulated antigen with a significantly higher humoral immune response (p-value = 0.047) when compared to the native, adjuvanted antigen. We propose dextran as a potential biopolymer with its co-excipient sodium chloride (NaCl) to provide protein compactness, i.e., prevent protein unfolding by molecular crowding or masking mechanism using preferential hydrophobic interaction for up to three weeks at room temperature (30 ± 2 °C).

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy. [ABSTRACT FROM AUTHOR]

A pharmaceutical formulation with favorable pharmacokinetic parameters is more likely to be efficacious and safe to overcome the failures of the drug resulting from lack of efficacy, poor bioavailability, and toxicity. In this view, we aimed to evaluate the pharmacokinetic functionalities and safety margin of an optimized CS-SS nanoformulation (F40) by in vitro/in vivo methods. The everted sac technique was used to evaluate the improved absorption of a simvastatin formulation. In vitro protein binding in bovine serum and mice plasma was performed. The formulation's liver and intestinal CYP3A4 activity and metabolic pathways were investigated by the qRT-PCR technique. The excretion of cholesterol and bile acids was measured to demonstrate the formulation's cholesterol depletion effect. Safety margins were determined by histopathology as well as fiber typing studies. In vitro protein binding results revealed the existence of a high percentage of free drugs (22.31 ± 3.1%, 18.20 ± 1.9%, and 16.9 ± 2.2%, respectively) compared to the standard formulation. The controlled metabolism in the liver was demonstrated from CYP3A4 activity. The formulation showed enhanced PK parameters in rabbits such as a lower Cmax, clearance, and a higher Tmax, AUC, Vd, and t1/2. qRT-PCR screening further proved the different metabolic pathways followed by simvastatin (SREBP-2) and chitosan (PPAR-γ pathway) in the formulation. The results from qRT-PCR and histopathology confirmed the toxicity level. Hence, this pharmacokinetic profile of the nanoformulation proved it has a unique synergistic hypolipidemic modality. [ABSTRACT FROM AUTHOR]

The present work deals with the preparation and characterization of lignin based macromolecular polymeric composites and applications thereof. Here lignin is complexed with pectin and/ or gellan gum, to form two different macromolecular green composites LP and LPG. The best ratios screened out through evaluation of nanoparticle characterization and rheology, then confirmed by surface morphology. The superior thermal stability is proved by DSC analysis. The reaction groups involving in complexation are confirmed by FT‐IR spectroscopic evaluation where the methoxy or methyl group of lignin interacts with the hydroxyl group of pectin and gellan gum to form nanocomposites. The reduced particle size and surface charge confirm the complexation due to interaction between ionizable functional groups. The applications of these composites are validated by their dye adsorption capacity and anti‐microbial properties (after loading of green silver nanoparticles) which proves the multifunctional properties of novel composites. The maximum dye removal efficiency of both composites is independent of initial dye concentration. Dye adsorption capacity is best fitted by Freundlich adsorption isotherms that follow pseudo‐second‐order adsorption kinetics. The antibacterial study of developed silver nanoparticle loaded and unloaded composites shows wide spectrum activity against E. coli and S. aureus, with higher inhibition efficiency against gram‐negative organism. [ABSTRACT FROM AUTHOR]

Objective and methods: This study predicted the nature of chitosan interactions and effects of this interaction on drug release mechanism in simvastatin-loaded chitosan nanoformulation using molecular docking, spectroscopic and thermal analysis. Significance: This work explains in depth the molecular mechanism of simvastatin and chitosan bond formation in nanoformulation. Results: The effective encapsulation and sustain release properties of chitosan were indicated by increase in melting endotherm of simvastatin. Intermolecular hydrogen bond between third hydroxyl group pyranone ring of simvastatin and amino group of chitosan represented the stability of active lactone moiety that was not cleaved during formulation which is prerequisite for biological activity. UV–vis spectroscopic characterization, shift in infrared vibration wavenumber of simvastatin and chitosan, ligand titration, 1HNMR and 13C-NMR analyses confirmed this interaction pattern. The pharmacokinetic evaluation in mouse model revealed the sustain release property of nanoformulation. Conclusion: Thus formation of intermolecular hydrogen bond in nanoformulation contributed to modified physicochemical properties and improved in vivo performance of simvastatin. [ABSTRACT FROM AUTHOR]