Grahame Mackenzie

Sporopollenin micro-reactors for in-situ preparation, encapsulation and targeted delivery of active components

We report a simple and robust technique for loading of sporopollenin microcapsules from Lycopodium clavatum with a range of inorganic and organic nanomaterials based on in-situ preparation of nanoparticles by a chemical reaction in the sporopollenin interior.

Palladium-catalyzed Suzuki reaction in aqueous solvents applied to unprotected nucleosides and nucleotides

Nucleoside analogues have attracted much attention due to their potential biological activities. Amongst all synthetic nucleosides, C5-modified pyrimidines and C2- or C8-modified purines have been particularly studied. A large variety of palladium cross-coupling reactions, with a majority of them based on the Suzuki–Miyaura reaction, have been developed for preparing the desired nucleoside derivatives. Our objective is to focus this review on the Suzuki–Miyaura cross-coupling of nucleosides using methodologies compatible with green chemistry and sustainable development for one part and bioorthogonality for the other part, which means using aqueous medium and no protection/deprotection steps.

Liquid crystals with restricted molecular topologies: supermolecules and supramolecular assemblies

The term liquid crystal is often associated with fascinating compounds that exhibit unusual melting or solubilisation properties, however, it also represents a unique collection of mesophases that exist between the solid state and the amorphous liquid. As such, this unique state of matter can be accessed by a wide variety of materials from low molar mass to polymeric systems. In this Feature Article we describe some recent studies concerning the liquid-crystalline behaviour of ‘in-between’ materials that have discrete molecular structures, and which are oligomeric but not low molar mass or polymeric systems. Thus, these materials could be described as having supermolecular architectures. We examine some of their mesophase properties and their abilities to form supramolecular assemblies. The development of liquid crystals that have large molecular structures or consist of large scale assemblies is one step towards creating novel self-organising systems which are of a similar dimension to certain biological materials, such as proteins.

Viability of plant spore exine capsules for microencapsulation

Sporopollenin exine capsules (SECs) (outer exoskeletal wall of the spores of Lycopodium clavatum) were extracted and examined for their potential use as microcapsules. They were shown, by laser scanning confocal microscopy (LSCM), to be void of their inner contents. The removal of nitrogenous and other internal materials was supported by a combination of elemental and gravimetric analyses. Two different methods were investigated to encapsulate substances into SECs which were (i) mild passive migration of materials into the SECs and (ii) subjecting SECs and materials to a vacuum. A range of fluorescent dyes with different polarities were seen using LSCM to encapsulate efficiently into the SECs (up to 1 g.g−1). Relatively unstable materials with different polarities were encapsulated into the SECs: polyunsaturated oils, which are labile to oxidation, and the enzymes streptavidin-horseradish peroxidase (sHRP) and alkaline phosphatase (ALP). Irrespective of the encapsulation techniques employed no oxidation of the oils or denaturation of the enzymes was observed following their full recovery. This study gives the first indication of the viability of SECs to microencapsulate various potentially unstable materials without causing a detrimental effect.

Protein free microcapsules obtained from plant spores as a model for drug delivery: ibuprofen encapsulation, release and taste masking

Sporopollenin exine capsules (SEC) extracted from Lycopodium clavatum spores were shown to encapsulate ibuprofen as a drug model, with 97 ± 1% efficiency as measured by recovery of the loaded drug and absence of the drug on the SEC surface by scanning electron microscopy (SEM). The encapsulated ibuprofen was shown to be unchanged from its bulk crystalline form by solid state NMR, FTIR and XRD. Essential for drug delivery applications, SEC were shown to be non-toxic to human endothelial cells and free of allergenic protein epitopes by MALDI-TOF-MS and ESI-QqToF-MS. Potential application for targeted release into the intestinal region of the gastrointestinal tract (GIT) was demonstrated by 88 ± 1% of the drug being retained in simulated gastric fluid (SGF) after 45 minutes and 85 ± 2% being released after 5 min in buffer (PBS; pH 7.4). The SEC were shown to provide significant taste masking of encapsulated ibuprofen in a double blind trial with 10 human volunteers.

Hollow pollen shells to enhance drug delivery

Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly of sporopollenin. The relative proportion of each varies according to the plant species. The structure of sporopollenin has not been fully characterised but different studies suggest the presence of conjugated phenols, which provide antioxidant properties to the microcapsule and UV (ultraviolet) protection to the material inside it. These microcapsule shells have many advantageous properties, such as homogeneity in size, resilience to both alkalis and acids, and the ability to withstand temperatures up to 250 °C. These hollow microcapsules have the ability to encapsulate and release actives in a controlled manner. Their mucoadhesion to intestinal tissues may contribute to the extended contact of the sporopollenin with the intestinal mucosa leading to an increased efficiency of delivery of nutraceuticals and drugs. The hollow microcapsules can be filled with a solution of the active or active in a liquid form by simply mixing both together, and in some cases operating a vacuum. The active payload can be released in the human body depending on pressure on the microcapsule, solubility and/or pH factors. Active release can be controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell.

MRI contrast agent delivery using spore capsules: controlled release in blood plasma

The exine coatings of spores can be used to encapsulate drug molecules. We have demonstrated that these microcapsules can be filled with a commercial gadolinium(III) MRI contrast agent (in this proof of concept study Gd-DTPA-BMA was used) which is slowly released in plasma due to enzymatic digestion of the capsule.

UV and visible light screening by individual sporopollenin exines derived from Lycopodium clavatum (club moss) and Ambrosia trifida (giant ragweed).

We have investigated the UV-visible light transmission of three types of micrometre-sized sporopollenin exine shells, two derived from Lycopodium clavatum (club moss) spores and one from Ambrosia trifida (giant ragweed) pollen. We have used spectrophotometer measurements of partial monolayers of exines and microscope absorbance imaging to derive the light transmission properties of individual exines. Measurements have been made for exines in air when light transmission losses are due to a combination of absorption, reflection and scattering processes and for exines dispersed in a liquid for which the refractive index (RI) is approximately equal to the RI of the exine such that reflection and scattering effects are negligible. Overall, it found that the light transmission of a single exine wall is approximately 50%. This value of the transmission is due mainly to light absorption, is similar for the three exines studied here and varies only slightly with light wavelength over the range 200-900 nm.

Self-Organization and Formation of Liquid Crystal Phases by Molecular Templates Related to Membrane Components of Archaebacteria

Tubular supramolecular aggregates are formed from glycolipids 1, which are closely related to natural components of membranes of archaebacteria. The glycolipids exhibit disordered columnar thermotropic and hexagonal lyotropic liquid crystal phases. Whereas formation of the mesophases is insensitive to stereochemical factors, formation of the tubules is dependent on the configuration of the stereocenters that are shown in the picture but not specified.

The effect of molecular shape on the liquid crystal properties of the mono-O-(2-hydroxydodecyl)sucroses

In this study we have varied the position of attachment of an aliphatic chain to a disaccharide sucrose unit, and we have shown that the point of attachment can markedly influence the self-organising properties and structure and bonding features of the material. The location of the attachment can introduce curvature into the system thereby stabilising certain structures over others. The results obtained for the thermotropic liquid crystalline properties of the mono-O-(2-hydroxydodecyl)sucroses show a similar dependency on molecular shape and curvature as those found in general for lyotropic systems.