Domain-selective thermal decomposition within supramolecular nanoribbons

Self-assembly of small molecules in water provides a powerful route to nanostructures with pristine molecular organization and small dimensions (<10 nm). Such assemblies represent emerging high surface area nanomaterials, customizable for biomedical and energy applications. However, to exploit self-assembly, the constituent molecules must be sufficiently amphiphilic and satisfy prescribed packing criteria, dramatically limiting the range of surface chemistries achievable. Here, we design supramolecular nanoribbons that contain: (1) inert and stable internal domains, and (2) sacrificial surface groups that are thermally labile, and we demonstrate complete thermal decomposition of the nanoribbon surfaces. After heating, the remainder of each constituent molecule is kinetically trapped, nanoribbon morphology and internal organization are maintained, and the nanoribbons are fully hydrophobic. This approach represents a pathway to form nanostructures that circumvent amphiphilicity and packing parameter constraints and generates structures that are not achievable by self-assembly alone, nor top-down approaches, broadening the utility of molecular nanomaterials for new targets.

The influence of lipid digestion on the fate of orally administered drug delivery vehicles

This review will focus on orally administered lipid-based drug delivery vehicles and specifically the influence of lipid digestion on the structure of the carrier lipids and their entrained drug cargoes. Digestion of the formulation lipids, which are typically apolar triglycerides, generates amphiphilic monoglycerides and fatty acids that can self-assemble into a diverse array of liquid crystalline structures. Tracking the dynamic changes in self-assembly of the lipid digestion products during digestion has recently been made possible using synchrotron-based small angle X-ray scattering. The influence of lipid chain length and degree of unsaturation on the resulting lipid structuring will be described in the context of the critical packing parameter theory. The chemical and structural transformation of the formulation lipids can also have a dramatic impact on the physical state of drugs co-administered with the formulation. It is often assumed that the best strategy for drug development is to maximise drug solubility in the undigested formulation lipids and to incorporate additives to maintain drug solubility during digestion. However, it is possible to improve drug absorption using lipid digestion in cases where the solubility of the dosed drug or one of its polymorphic forms is greater in the digested lipids. Three different fates for drugs administered with digestible lipid-based formulations will be discussed: (1) where the drug is more soluble in the undigested formulation lipids; (2) where the drug undergoes a polymorphic transformation during lipid digestion; and (3) where the drug is more soluble in the digested formulation lipids.

Structure optimization of lipopeptide assemblies for aldol reactions in an aqueous medium

Guanidiniocarbonyl pyrrole (GCP) conjugated lipopeptides improve aldol reaction catalysis by enhanced the molecules packing parameter, as shown by SAXS data and molecular dynamics simulations.

Highly Sustainable and Completely Amorphous Hierarchical Ceramide Microcapsules for Potential Epidermal Barrier

As a main component of the stratum corneum, ceramides can construct protective lamellae to provide an epidermal barrier against dehydration or external microorganisms. However, as ceramide molecules can easily form the isolated crystalline phase through self-assembly due to the amphipathic nature of bioactive lipids, the effective incorporation of ceramides into liquid media is the remaining issue for controlled release. Here, we report an unprecedented effective strategy to fabricate a completely amorphous and highly sustainable hierarchical ceramide polymer microcapsule for promising epidermal barrier by using the interpenetrating and cooperative self-construction of conical amphiphiles with a different critical packing parameter. The self-constructed amorphous architecture of ceramides in polymer microcapsule is achieved by the facile doping of conical amphiphiles and subsequent in situ polymerization of shell polymer in the core-shell geometry. It is experimentally revealed that an irregular cooperative packing structure formed by adaptive hydrophobic–hydrophilic interactions of cylindrical ceramides and conical amphiphiles in the confined microcapsule geometry enables a completely amorphous morphology of ceramides to be realized during the spontaneous encapsulation process. Furthermore, this elegant approach affords a highly dispersible and uniform hierarchical amorphous ceramide microcapsule with a greatly enhanced long-term stability compared to conventional crystalline ceramides.

Designing Sub-20 nm Nanocarriers for Small Molecule Delivery: Interplay among Structural Geometry, Assembly Energetics, and Cargo Release Kinetics

Biological constraints in diseased tissues have motivated the need for small nanocarriers (10-30 nm) to achieve sufficient vascular extravasation and pervasive tumor penetration. This particle size limit is only an order of magnitude larger than small molecules, such that cargo loading is better described by co-assembly processes rather than simple encapsulation. Understanding the structural, kinetic, and energetic contributions of carrier-cargo co-assembly is thus critical to achieve molecular-level control and predictable in vivo behavior. These interconnected set of properties were systematically examined using sub-20 nm self-assembled nanocarriers known as three-helix micelles (3HM). Both hydrophobicity and the “geometric packing parameter” dictate small molecule compatibility with 3HM’s alkyl tail core. Planar obelisk-like apomorphine and doxorubicin (DOX) molecules intercalated well within the 3HM core and near the core-shell interface, forming an integral component to the co-assembly, as corroborated by small angle X-ray and neutron-scattering structural studies. DOX promoted crystalline alkyl tail ordering, which significantly increased (+63%) the activation energy of 3HM subunit exchange. Subsequently, 3HM-DOX displayed slow-release kinetics (t1/2=40 h) at physiological temperatures, with ~50x greater cargo preference for the micelle core as described by two drug partitioning coefficients (micellar core/shell Kp1 ~24, and shell/bulk solvent Kp2 ~2). The geometric and energetic insights between nanocarrier and their small molecule cargos developed here will aid in broader efforts to deconvolute the interconnected properties of carrier-drug co-assemblies, and to understand nanomedicine behavior throughout all the physical and in vivo processes they are intended to encounter.

Interfacial and Micellization Behavior of Cetyltrimethylammonium Bromide (CTAB) in Water and Methanol-Water Mixture at 298.15 to 323.15 K

The micellization behavior of cetyltrimethylammonium bromide (CTAB) in water , 0.1, 0.2, 0.3, and 0.4 volume fractions of methanol at 298.15, 308.15, 318.15, and 323.15 K were investigated by surface tension measurements. The effect of methanol on values of critical micelle concentration (cmc), free energies of micellization ΔGmo, and surface properties viz. maximum surface excess concentration Γmax, area occupied by per surfactant molecule Amin, surface pressure πcmc, solution surface tension γcmc, solvent surface tension (γo), free energies of adsorption ΔGadso, the efficiency of adsorption (pC20), effective Gibbs free energy ΔGeffo, and free energy of surface at equilibrium (Gmin) were investigated using surface tension values. Other parameters such as the packing parameter (P), aggregation number (N), concentration of surfactant in the bulk phase (C20), relation between Amin and πcmc, and correlation of slopes dγ/d log C, γo/γcmc, Γ/Γmax, cmc/C20, ΔGadso/ΔGmo, and cmc/pC20 with the volume fraction of methanol are calculated and discussed in the light of the experiment done.

Encapsulation of Vitamin C in Sesame Liposomes: Computational and Experimental Studies

An experimental and computational study was carried out for encapsulation of vitamin C in sesame, Sesamum indicum L., liposomes. Based on computational studies, the packing parameter (P) of sesame phospholipids was found to be 0.64 ± 0.09. This indicates that the molecular shape of sesame phospholipids is in the form of truncated cone and, in aqueous solution, it self-assembles to form liposomes. In the liposomes, no chemical interaction was observed between phospholipid molecules and vitamin C. However, medium-strength hydrogen bonds (Ei) from -87.6 kJ/mol to -82.02 kJ/mol with bond lengths ranging from 1.746 Å to 1.827 Å were formed between vitamin C and phospholipid molecules. Because of this weak interaction, vitamin C gets released easily from the inner regions of liposome. Empirical experiments were performed to confirm the computation outcomes, where sesame liposomes were found to encapsulate almost 80% of vitamin C in their interior cavities. During the 8 days storage, release of vitamin C occurred gradually from the liposome system, which signifies week interactions in the liposome membranes amongst phospholipid molecules and vitamin C.

Sweet surfactants: packing parameter-invariant amphiphiles as emulsifiers and capping agents for morphology control of inorganic particles

Exploration of isomer effects on amphiphile properties (e.g.emulsification and as nanoparticle growth modifiers) using a library of glycoside-based surfactants.