Hybrid hydrogels derived from renewable resources as a smart stimuli responsive soft material for drug delivery applications

The design and synthesis of amphiphilic molecules play a crucial role in fabricating smart functional materials via self-assembly.

Drug-Induced Phase Separation in Polyelectrolyte Microgels

Polyelectrolyte microgels may undergo volume phase transition upon loading and the release of amphiphilic molecules, a process important in drug delivery. The new phase is “born” in the outermost gel layers, whereby it grows inward as a shell with a sharp boundary to the “mother” phase (core). The swelling and collapse transitions have previously been studied with microgels in large solution volumes, where they go to completion. Our hypothesis is that the boundary between core and shell is stabilized by thermodynamic factors, and thus that collapsed and swollen phases should be able to also coexist at equilibrium. We investigated the interaction between sodium polyacrylate (PA) microgel networks (diameter: 400–850 µm) and the amphiphilic drug amitriptyline hydrochloride (AMT) in the presence of NaCl/phosphate buffer of ionic strength (I) 10 and 155 mM. We used a specially constructed microscopy cell and micromanipulators to study the size and internal morphology of single microgels equilibrated in small liquid volumes of AMT solution. To probe the distribution of AMT micelles we used the fluorescent probe rhodamine B. The amount of AMT in the microgel was determined by a spectrophotometric technique. In separate experiments we studied the binding of AMT and the distribution between different microgels in a suspension. We found that collapsed, AMT-rich, and swollen AMT-lean phases coexisted in equilibrium or as long-lived metastable states at intermediate drug loading levels. In single microgels at I = 10 mM, the collapsed phase formed after loading deviated from the core-shell configuration by forming either discrete domains near the gel boundary or a calotte shaped domain. At I = 155 mM, single microgels, initially fully collapsed, displayed a swollen shell and a collapsed core after partial release of the AMT load. Suspensions displayed a bimodal distribution of swollen and collapsed microgels. The results support the hypothesis that the boundary between collapsed and swollen phases in the same microgel is stabilized by thermodynamic factors.

Phospholipids: Identification and Implication in Muscle Pathophysiology

Phospholipids (PLs) are amphiphilic molecules that were essential for life to become cellular. PLs have not only a key role in compartmentation as they are the main components of membrane, but they are also involved in cell signaling, cell metabolism, and even cell pathophysiology. Considered for a long time to simply be structural elements of membranes, phospholipids are increasingly being viewed as sensors of their environment and regulators of many metabolic processes. After presenting their main characteristics, we expose the increasing methods of PL detection and identification that help to understand their key role in life processes. Interest and importance of PL homeostasis is growing as pathogenic variants in genes involved in PL biosynthesis and/or remodeling are linked to human diseases. We here review diseases that involve deregulation of PL homeostasis and present a predominantly muscular phenotype.

Formation of Amphiphilic Molecules from the Most Common Marine Polysaccharides, toward a Sustainable Alternative?

Marine polysaccharides are part of the huge seaweeds resources and present many applications for several industries. In order to widen their potential as additives or bioactive compounds, some structural modifications have been studied. Among them, simple hydrophobization reactions have been developed in order to yield to grafted polysaccharides bearing acyl-, aryl-, alkyl-, and alkenyl-groups or fatty acid chains. The resulting polymers are able to present modified physicochemical and/or biological properties of interest in the current pharmaceutical, cosmetics, or food fields. This review covers the chemical structures of the main marine polysaccharides, and then focuses on their structural modifications, and especially on hydrophobization reactions mainly esterification, acylation, alkylation, amidation, or even cross-linking reaction on native hydroxyl-, amine, or carboxylic acid functions. Finally, the question of the necessary requirement for more sustainable processes around these structural modulations of marine polysaccharides is addressed, considering the development of greener technologies applied to traditional polysaccharides.

Biosurfactants from Soil Microorganisms as a Possible Detergent Replacement

Biosurfactants belong to the amphiphilic molecules category and are formed by a range of microorganisms. Similar to chemical surfactants, properties of Biosurfactants that make them unique include minimizing the surface and interfacial tensions. Biosurfactants also have Critical Micelle Concentration (CMC) in organic and aqueous solutions. Recent studies confirm the toxic nature of chemically synthesized surfactants and the advantages of biosurfactants prove their potential than commercially artificial counterparts. Rhamnolipids are well-characterized and promising compounds among other biosurfactants. In this study, biosurfactants producing microorganisms were isolated from the soil. The isolated microorganism was identified with different biochemical tests and found to be Pseudomonas aeruginosa. 16s rRNA locus was utilized for DNA bar-coding. Production of biosurfactants was done at shake flask level and 5L lab-scale fermenter using minimal media optimized for high yield. Cell-free supernatant was purified using LLE and biosurfactants characterization was performed on HPTLC and HPLC using standard Rhamnolipids. The isolated biosurfactants were tested to remove common stains and were found effective. This shows the potential of biosurfactants as a Laundry detergent.

A general approach on the surfactants use and their properties in drug delivery systems

: Surfactants are amphiphilic molecules of great interest in the pharmaceutical field due to their use in combination with other adjuvants to solubilize poor soluble drugs, improve their dissolution profile, promote permeation, increase drug delivery systems stabilization, among other characteristics. Literature shows that surfactants are included in several pharmaceutical forms composition: tablets, solid dispersions, emulsions, microemulsions, nanoemulsions, liposomes, and niosomes. This review aims to elucidate the different classes of surfactants based on their charges (cationic, anionic, nonionic, zwitterionic, and dimeric), the micelles formation process, and how surfactants molecules geometry can affect this phenomenon. Moreover, current studies regarding the benefits of surfactants in the development of formulations are presented. Finally, a discussion on how charges and chain length of surfactants can interact with the stratum corneum epithelial cells leading to increased permeation or skin irritability is reported.

Mechanistic Insights on ATP’s role as Hydrotrope

Hydrotropes are small amphiphilic molecules which help in solubilizing hydrophobic entities in aqueous medium. Recent experimental investigation has provided convincing evidences that, adenosine triphosphate (ATP), besides being an energy currency of cell, also can act as hydrotrope to inhibit the formation of protein condensates. In this work, we have designed computer simulations of prototypical macromolecules in aqueous ATP solution to dissect the molecular mechanism underlying ATP’s newly discovered role as a hydrotrope. The simulation demonstrates that ATP can unfold a single-chain of hydrophobic macromolecule as well as can disrupt the aggregation process of a hydrophobic assembly. Moreover, the introduction of charges in the macromolecule is found to reinforce ATP’s disaggregation effects in a synergistic fashion, a behaviour reminiscent of recent experimental observation of pronounced hydrotropic action of ATP in intrinsically disordered proteins. A molecular analysis indicates that this new-found ability of ATP are ingrained in its propensity of preferential binding to the polymer surface, which gets fortified in presence of charges. The investigation also renders evidence that the key to the ATP’s superior hydrotropic role over chemical hydrotrope (Sodium xylene sulfonate, NaXS) may lie in its inherent self-aggregation propensity. Overall, via employing a bottom-up approach the current investigation provides fresh mechanistic insights into the dual solubilizing and denaturing abilities of ATP.

Predicting Critical Micelle Concentrations for Surfactants using Graph Convolutional Neural Networks

Surfactants are amphiphilic molecules that are widely used in consumer products, industrial processes, and biological applications. A critical property of a surfactant is the critical micelle concentration (CMC), which is the concentration at which surfactant molecules undergo cooperative self-assembly in solution. Notably, the primary method to obtain CMCs experimentally—tensiometry—is laborious and expensive. In this work, we show that graph convolutional neural networks (GCNs) can predict CMCs directly from the surfactant molecular structure. Specifically, we developed a GCN architecture that encodes the surfactant structure in the form of a molecular graph and trained it using experimental CMC data. We found that the GCN can predict CMCs with higher accuracy than previously proposed methods and that it can generalize to anionic, cationic, zwitterionic, and nonionic surfactants. Molecular saliency maps revealed how atom types and surfactant molecular substructures contribute to CMCs and found this to be in agreement with physical rules that correlate constitutional and topological information to CMCs. Following such rules, we proposed a small set of new surfactants for which experimental CMCs are not available; for these molecules, CMCs predicted with our GCN exhibited similar trends to those obtained from molecular simulations. These results provide evidence that GCNs can enable high-throughput screening of surfactants with desired self-assembly characteristics.