Fabrication and Characterization of Electrospun Ocimum sanctum and Curcumin-Loaded Nanofiber Membrane for the Management of Periodontal Disease: An In Vitro Study.

Background Periodontal disease is a chronic inflammatory condition that gradually deteriorates the supportive tissues of teeth, eventually leading to tooth loss. Mechanical debridement stands as the gold standard method for treating periodontitis. However, antimicrobial therapy is recommended for optimal results when used alongside mechanical debridement. Numerous studies have investigated local drug delivery as an adjunct to mechanical debridement of affected tooth surfaces. Ocimum sanctum exhibits anti-inflammatory, antioxidant, and antimicrobial properties. Similarly, curcumin, as documented in the literature, demonstrates a broad spectrum of anti-inflammatory and antimicrobial effects. Electrospinning has demonstrated itself to be a highly effective method for fabricating drug-loaded fibers. Electrospun nanofibers containing Ocimum sanctum and curcumin are expected to exhibit greater efficacy due to their increased surface area, facilitating the dispersion of larger quantities of drugs, and their ability to control drug release when employed as a local drug delivery system. This study aims to fabricate and characterize the properties of nanofiber membranes loaded with Ocimum sanctum and curcumin using the electrospinning technique. Methods About 50 mg each of Ocimum sanctum and curcumin were blended with 15% polyvinyl alcohol and 2% chitosan polymer in a 4:1 ratio and left to stir overnight. A 10 mL syringe was filled with this solution, and an 18 G blunt-end needle charged at 15.9 kV was used for extrusion. Continuous fibers were collected onto a collector plate positioned 12 cm from the center of the needle tip, at a flow rate of 0.005 mL/min. The morphology of the fabricated membrane was assessed through scanning electron microscopy (SEM), the strength of the material was assessed through tensile strength analysis using INSTRON, an Electropuls E3000 Universal Testing Machine (INSTRON, Norwood, MA), and the drug release pattern was analyzed using Jasco V-730 UV-visible spectrophotometer (Jasco, Easton, MD). Results The morphology of this nanofiber showed a random distribution of fibers with no bead formation. The average diameter of the membrane was 383±102 nm, and the tensile strength of this material was 1.87 MPa. The drug release pattern showed an initial burst release of Ocimum sanctum, followed by a controlled release in subsequent hours. However, curcumin showed very little drug release because of its solubility. Conclusion In summary, the Ocimum sanctum and curcumin-loaded nanofibers exhibited robust tensile strength, a controlled drug release profile, and uniform drug distribution within the nanofiber membrane. Consequently, it can be concluded that curcumin nanofibers and electrospun Ocimum sanctum serve as valuable agents for local drug delivery in the treatment of periodontitis.

Self-Assembly of Cysteine into Nanofibrils Precedes Cystine Crystal Formation: Implications for Aggregation Inhibition.

The self-association of metabolites into well-ordered assemblies at the nanoscale has significant biological and medical implications. The thiol-containing amino acid cysteine (CYS) can assemble into amyloid-like nanofibrils, and its oxidized form, the disulfide-bonded cystine (CTE), forms hexagonal crystals as those found in cystinuria due to metabolic disorder. Yet, there have been no attempts to connect these two phenomena, especially the fibril-to-crystal transition. Here, we reveal that these are not separated events, and the CYS-forming amyloid fibrils are mechanistically linked to hexagonal CTE crystals. For the first time, we demonstrated that cysteine fibrils are a prerequisite for forming cystine crystals, as observed experimentally. To further understand this mechanism, we studied the effects of thiol-containing cystinuria drugs (tiopronin, TIO; and d-penicillamine, PEN) and the canonical epigallocatechin gallate (EGCG) amyloid inhibitor on fibril formation by CYS. The thiol-containing drugs do not solely interact with monomeric CYS via disulfide bond formation but can disrupt amyloid formation by targeting CYS oligomers. On the other hand, EGCG forms inhibitor-dominant complexes (more than one EGCG molecule per cysteine unit) to prevent CYS fibril formation. Interestingly, while CYS can be oxidized into CTE, the thiol drugs can reduce CTE back to CYS. We thus suggest that the formation of crystals in cystinuria could be halted at the initial stage by targeting CYS fibril formation as an alternative to solubilizing the water-insoluble hexagonal CTE crystals at a later stage. Taken together, we depicted a complex hierarchical organization in a simple amino acid assembly with implications for therapeutic intervention.

Hydrogen trapping and embrittlement in high-strength Al alloys.

Ever more stringent regulations on greenhouse gas emissions from transportation motivate efforts to revisit materials used for vehicles1. High-strength aluminium alloys often used in aircrafts could help reduce the weight of automobiles, but are susceptible to environmental degradation2,3. Hydrogen 'embrittlement' is often indicated as the main culprit4; however, the exact mechanisms underpinning failure are not precisely known: atomic-scale analysis of H inside an alloy remains a challenge, and this prevents deploying alloy design strategies to enhance the durability of the materials. Here we performed near-atomic-scale analysis of H trapped in second-phase particles and at grain boundaries in a high-strength 7xxx Al alloy. We used these observations to guide atomistic ab initio calculations, which show that the co-segregation of alloying elements and H favours grain boundary decohesion, and the strong partitioning of H into the second-phase particles removes solute H from the matrix, hence preventing H embrittlement. Our insights further advance the mechanistic understanding of H-assisted embrittlement in Al alloys, emphasizing the role of H traps in minimizing cracking and guiding new alloy design.

Understanding Alkali Contamination in Colloidal Nanomaterials to Unlock Grain Boundary Impurity Engineering.

Metal nanogels combine a large surface area, a high structural stability, and a high catalytic activity toward a variety of chemical reactions. Their performance is underpinned by the atomic-level distribution of their constituents, yet analyzing their subnanoscale structure and composition to guide property optimization remains extremely challenging. Here, we synthesized Pd nanogels using a conventional wet chemistry route, and a near-atomic-scale analysis reveals that impurities from the reactants (Na and K) are integrated into the grain boundaries of the poly crystalline gel, typically loci of high catalytic activity. We demonstrate that the level of impurities is controlled by the reaction condition. Based on ab initio calculations, we provide a detailed mechanism to explain how surface-bound impurities become trapped at grain boundaries that form as the particles coalesce during synthesis, possibly facilitating their decohesion. If controlled, impurity integration into grain boundaries may offer opportunities for designing new nanogels.

A supramolecular hydrogel derived from a simple organic salt capable of proton conduction.

The supramolecular hydrogel of a simple organic salt derived from a primary amine and a mono-sulfonic acid displayed a proton conductivity of 1.2 × 10-4 S cm-1. The hitherto unknown example of the supramolecular gel displaying proton conductivity provides an intriguing alternative to liquid electrolyte or polymer gel electrolytes.

An easy access to topical gels of an anti-cancer prodrug (5-fluorouracil acetic acid) for self-drug-delivery applications.

An easy access to topical gels (both hydro- and organogels) derived from an anti-cancer prodrug namely 5-fluorouracil acetic acid (5-FuA) achieved by exploiting a simple salt formation strategy is reported for the first time. Nearly 85% of the salts synthesized were gelators. Single crystal structures of some of the gelator salts revealed an intriguing hydrogen bonding network including double stranded 1D chains stabilized through uracil-uracil complementary interactions and the crystal structures of the gelator salts corroborated well with the hypothesis based on which the gelators were designed. Studies indicated that both the hydrogel and the methyl salicylate gel of the gelator salt FuA-15 were suitable for self-drug-delivery application.

Exploring Orthogonal Hydrogen Bonding towards Designing Organic-Salt-Based Supramolecular Gelators: Synthesis, Structures, and Anticancer Properties.

A series of primary ammonium monocarboxylate (PAM) salts derived from ß-alanine derivatives of pyrene and naphthalene acetic acid, along with the parent acids, were explored to probe the plausible role of orthogonal hydrogen bonding resulting from amide⋅⋅⋅amide and PAM synthons on gelation. Single-crystal X-ray diffraction (SXRD) studies were performed on two parent acids and five PAM salts in the series. The data revealed that orthogonal hydrogen bonding played an important role in gelation. Structure-property correlation based on SXRD and powder X-ray diffraction data also supported the working hypothesis upon which these gelators were designed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell migration assay on a highly aggressive human breast cancer cell line, MDA-MB-231, revealed that one of the PAM salts in the series, namely, PAA.B2, displayed anticancer properties, and internalization of the gelator salt in the same cell line was confirmed by cell imaging.