Daniel S. Eldridge

Physicochemical characterization of solid lipid nanoparticles (SLNs) prepared by a novel microemulsion technique

HYPOTHESIS Solid lipid nanoparticles (SLNs) produced by conventional microemulsion techniques using thermal heat have specific limitations (e.g. high polydispersity, instability and low encapsulation). Replacing thermal heat with microwave heat may produce SLNs which overcome some of these limitations. EXPERIMENTS Stearic acid-based SLNs prepared with Tween® 20 as the emulsifier were chosen as the optimum formulation to encapsulate and potentially deliver the antibacterial drug tetracycline. All formulations were characterized for their particle size, zeta potential, encapsulation efficiency, loading capacity, thermal and X-ray diffraction analyses. Short-term stability and in vitro drug studies were also performed. FINDINGS Microwave heating helps to overcome several disadvantages associated with thermal heating (nonuniform, inefficient and slow) and results in improved particle characteristics. There is thus the potential for new opportunities in the development of colloidal carriers. The particle sizes of microwave-produced SLNs were in the desired nanometer range (200-250 nm) with both lower size and lower polydispersity than the conventional SLNs. We take this as an indication of improved stability; however zeta potential measurements were not different, indicating similar stability. True stability testing (visual observation with time) did show that the microwave-induced SLNs were found to be more stable, particularly when refrigerated. The microwave-produced SLNs also demonstrated improved encapsulation efficiency and loading capacity. Thermal and diffraction analysis confirmed a lowered crystallinity of stearic acid with successful incorporation of tetracycline into the SLNs. In vitro release studies indicated that, after an initial burst release, SLNs could provide prolonged release of tetracycline. The presence of tetracycline and non-toxicity of carriers towards microbes was confirmed by antimicrobial susceptibility tests.

Composition and Structure

Lipid nanoparticles, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), lipid-drug conjugates (LDC) and polymer-lipid hybrid nanoparticles (PLN), are colloidal carriers with a lipid matrix that is solid at body temperature. These colloidal carriers have attracted increasing interest for their use in therapeutic and cosmetic applications. The performance of lipid nanoparticle formulations is greatly influenced by their composition and structure. Lipid nanoparticles are generally composed of lipids, surfactants and co-surfactants. The lipid materials used in the production of lipid nanoparticles are usually solid at room temperature. Being well-tolerated in physiological conditions, lipid nanoparticles are typically biocompatible. Liquid lipids, or oils, are specifically used for production of NLCs. In most cases, lipid nanoparticles are produced as dispersions and surface-tailored with surfactants to improve dispersion stability. Polymers are often used to form polymer-lipid cores in the production of PLNs. Lipid nanoparticles are often used as sustained-release systems, with the structure of the lipid nanoparticles dictating their release properties. While the concentration of drug in lipid nanoparticle dispersions is quite well known, knowledge of the drug-lipid interaction in terms of the state and localization of the drug in the nanoparticle is still unknown. Several structural models of SLNs and NLCs have been proposed. The composition and structure of lipid nanoparticles—two critical factors that may influence their pharmaceutical performance—will be discussed in this chapter.

Transport of stearic acid-based solid lipid nanoparticles (SLNs) into human epithelial cells.

Development of drug delivery systems, as much as the drug molecule itself, is an important consideration for improving drug absorption and bioavailability. The mechanisms by which drug carriers enter target cells can differ depending on their size, surface properties and components. Solid lipid nanoparticles (SLNs) have gained an increased attention in recent years and are the drug carriers of interest in this paper. They are known to breach the cell-membrane barrier and have been actively sought to transport biomolecules. Previous studies by our group, and also other groups, provided an extensive characterization of SLNs. However, few studies have investigated the uptake of SLNs and these have had limited mechanistic focus. The aim of this work was to investigate the pathway of uptake of SLNs by human epithelial cells i.e., lung A549 and cervical HeLa cells. To the best of our knowledge, this is first study that investigates the cellular uptake of SLNs by human epithelial cells. The mechanism of cellular uptake was deciphered using pharmacologic inhibitors (sucrose, potassium-free buffer, filipin and cytochalasin B). Imaging techniques and flow assisted cell sorting (FACS) were used to assess the cellular uptake of SLNs loaded with rhodamine 123 as a fluorescent probe. This study provided evidence that the cellular uptake of SLNs was energy-dependent, and the endocytosis of SLNs was mainly dependent on clathrin-mediated mechanisms. The establishment of entry mechanism of SLNs is of fundamental importance for future facilitation of SLNs as biological or drug carriers.

The role of metal ion-ligand interactions during divalent metal ion adsorption

A suite of seven different divalent metal ions (Ca(II), Cd(II), Cu(II), Mg(II), Ni(II), Pb(II), Zn(II)) was adsorbed from solution onto two Fe2O3 samples, quartz SiO2 and three different amphoteric polystyrene latices (containing amine and carboxyl functional groups). For the metal oxides, a high correlation was observed between the pH at which 50% of the metal was removed from solution (pH50) and the first hydrolysis constant for the metal ion (pK1). For the polystyrene latices, a much higher correlation was observed between the pH50 and pKc (equilibrium constant describing metal-carboxyl affinity) as opposed to pK1. These observations provide evidence of a strong relationship that exists between a metals affinity for a particular ligand in solution and for that metal ions affinity for the same ligand present as part of an adsorbing surface. The isoelectric point of the amphoteric latex surface can be increased by decreasing the carboxyl content of the latex surface. For all 7 metal ions, this resulted in a substantial decrease, for any given pH, in adsorption. We suggest that this may be partly due to the decreased carboxyl content, but is dominantly attributable to the presence of less favorable electrostatic conditions. This, in turn, demonstrates that electrostatics play a controlling role in metal ion adsorption onto amphoteric latex surfaces and, in addition to the nature of the metal ion, also controls the pH at which adsorption takes place.

Structure of solid lipid nanoparticles produced by a microwave-assisted microemulsion technique

We have recently reported a novel microwave-assisted microemulsion technique for the production of solid lipid nanoparticles (SLNs). SLNs are colloidal carriers made from physiologically well-tolerated lipids that are normally solid at room and body temperature. These microwave-produced SLNs have small size, moderate zeta potential, high encapsulation efficiency and low crystallinity. The drug release studies conducted on drug-loaded SLNs are consistent with a core–shell structure for the microwave-produced SLNs, but with significantly different release profiles depending on the drug used. We further employed multi-angle static and dynamic light scattering (SLS/DLS) and small angle X-ray scattering (SAXS) techniques to help elucidate the structure of microwave-produced SLNs. The SLS/DLS data for the SLNs prepared in this study are consistent with a core–shell structure with a shell thickness of ∼13 nm. SAXS data suggest that the SLNs have a lipid lamellar structure with a repeat spacing of 41.0 ± 0.1 A.

Using a gamified mobile app to increase student engagement, retention and academic achievement

This study investigated whether the use of a gamified mobile learning app influenced students’ academic performance and boosted their engagement in the subject. Created to better engage students in lecture content, the app was used to deliver multiple-choice content-based quizzes directly to students’ personal mobile devices post-lecture and pre-tutorial. After measuring the relationships between students’ app usage and their engagement, retention and academic achievement in the subject, it is suggested that following the app’s introduction, student retention rates and academic performance increased, and there was a positive correlation between students’ scoring highly on the app and achieving higher academic grades. While the app’s affordances for learning are promising, the causal relationship between the app usage and improved student outcomes requires further investigation. Conclusions made in the context of the wider scholarship of mobile app enhanced learning and applied game principles in HE.

Microwave-assisted microemulsion technique for production of miconazole nitrate and econazole nitrate-loaded solid lipid nanoparticles

Graphical abstract Figure. No caption available. ABSTRACT The microwave‐assisted production of solid lipid nanoparticles (SLNs) is a novel technique reported recently by our group. The small particle size, solid nature and use of physiologically well‐tolerated lipid materials make SLNs an interesting and potentially efficacious drug carrier. The main purpose of this research work was to investigate the suitability of microwave‐assisted microemulsion technique to encapsulate selected ionic drug substances such as miconazole nitrate and econazole nitrate. The microwave‐produced SLNs had a small size (250–300 nm), low polydispersity (<0.20), high encapsulation efficiency (72–87%) and loading capacity (3.6–4.3%). Differential scanning calorimetry (DSC) and X‐ray diffraction (XRD) studies suggested reduced crystallinity of stearic acid in SLNs. The release studies demonstrated a slow, sustained but incomplete release of drugs (<60% after 24 h) from microwave‐produced SLNs. Data fitting of drug release data revealed that the release of both drugs from microwave‐produced SLNs was governed by non‐Fickian diffusion indicating that drug release was both diffusion‐ and dissolution‐ controlled. Anti‐fungal efficacy of drug‐loaded SLNs was evaluated on C. albicans. The cell viability studies showed that cytotoxicity of SLNs was concentration‐dependent. These encouraging results suggest that the microwave‐assisted procedure is suitable for encapsulation of ionic drugs and that microwave‐produced SLNs can act as potential carriers of antifungal drugs.

Surface functionalization and manipulation of mesoporous silica adsorbents for improved removal of pollutants: a review

Mesoporous silica (MS) has been one of the most versatile and successful adsorbents for the removal of environmental pollutants in recent years. The extent to which its structural properties can be tailored and the ease with which such morphological properties can be manipulated are widely acknowledged as major advantages of MS over other adsorbents. In addition to this, modifications to the surface of MS have also been explored in recent years. When the morphology and surface functionality of adsorbents are optimised, great improvements in selective adsorption capacities for a wide range of different pollutant types have been achieved. This review article will explore the most common functional groups deposited at adsorbent surfaces, and the reagents and methods used to deposit these groups to the MS surface, for the purpose of increasing the adsorption capacity and/or selectivity for both inorganic and organic wastewater pollutants. A selection of successful surface functionalizations which have been performed on different substrates will also be outlined, to guide future MS surface modifications.

The role of lecithin degradation on the pH dependent stability of halofantrine encapsulated fat nano-emulsions

We report on the successful incorporation of the antimalarial drug, halofantrine, into laboratory based soybean oil emulsions which were designed to mimic the commercially available parenteral fat emulsion, Intralipid®. A high pH (minimum of pH 9, preferable pH of 11) was required for the drug laden emulsion to remain stable on storage and also to resist breaking under various stresses. Ageing of lecithin samples on storage was noted to result in degradation and a decrease in pH. We argue that this is the main reason for a similar decrease in pH for lecithin based emulsions and subsequent instability in drug laden emulsions. As expected, incorporation of the drug (halofantrine) resulted in lower stability. The (intensity weighted) particle size increased from 281nm for the drug free emulsion to 550nm following a loading of 1gL-1 of halofantrine, indicative of a lowering in stability and this was reflected in a shorter shelf life. Interestingly, incorporation of even higher concentrations of drug then resulted in better stability albeit never as stable as the drug free emulsion. We also report on unusual and complex surface tension behaviour for fresh lecithin where multiple critical concentration points were observed.