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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 (250-300nm), 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 24h) 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Stearic acid-based solid lipid nanoparticles (SLNs) were prepared using the microwave assisted one-pot microemulsions procedure pioneered by our group. In this study, non-steroidal anti-inflammatory drugs (NSAIDs) including indomethacin, ketoprofen and nimesulide were selected as ideal "test" drugs, based on their poor water solubility. The model drugs were incorporated within the SLNs by the microwave-assisted procedure at the time of SLN production. The microwave-produced drug-loaded SLNs were evaluated in terms of their physicochemical characteristics, drug release behavior and their uptake into against A549 cell line (human lung epithelial cells). The microwave-produced drug-loaded SLNs had a small particle size distribution, negative zeta potential and high encapsulation efficiency. The drug release studies were consistent with a core-shell structure of SLNs (probably a drug-loaded shell) which results in biphasic drug release from the SLNs. The drug release kinetics suggested a good fit of the release data to the Makoid-Banakar model and was governed by Fickian diffusion. The drug-loaded SLNs showed concentration-dependent cytotoxicity and reduced IL-6 and IL-8 secretion in lipopolysaccharide-induced cells. All of the above findings suggest that the microwave-produced SLNs could be promising drug carriers of NSAIDs and will further facilitate their development for topical, oral and/or nasal administration., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Solid lipid nanoparticles (SLNs) are a well-tolerated lipid carrier system due to the employment of a physiological and/or biodegradable lipid matrix. Physicochemical properties such as particle size, polydispersity index (PI) and zeta potential are SLN quality response parameters. Increased particle size is a good indicator of in-vitro instability. This work focuses on the importance of selecting the lipid matrices and excipients that can achieve the particle size and stability required if such formulations are to be utilised in the pharmaceutical market. With the aim of understanding the influence of variation in SLN composition (lipid and emulsifier concentration), a Taguchi model of experimental design was applied. Tested factors included the concentration of lipid (stearic acid) and the concentration of Tween®20. SLNs were successfully prepared by a microemulsion-based technique. Based on the hydrophilic lipophilic balance (HLB), different combinations of emulsifiers/co-emulsifiers (Tween®20/Span®20, Tween®20/Span®80, Tween®20/n-butanol, and Tween®20/iso-propanol) were also used to control the physicochemical properties of SLNs. The influence of pH (addition of HCl or NaOH) and electrolyte (addition of NaCl), both during and after the preparation, were also investigated on selected SLN formulations. Slightly polydispersed (PI < 0.3) nanoparticles with a particle size < 450 nm and zeta potential range of +5 to -50 mV were developed. Physical stability of optimised stearic-acid based SLNs over 2 months were assessed by particle size measurement. SLNs were stable when refrigerated. These results suggest that thoughtful selection of lipid and lipid excipients is essential for successful preparation and physical stability of SLNs. This study facilitates the preliminary physicochemical characterisation for favourable encapsulation of lipophilic and hydrophilic drugs. [ABSTRACT FROM AUTHOR]

Suspensions of solid lipid nanoparticles (SLNs) stabilized with emulsifiers have been extensively investigated (since the 1990s) as drug carriers, although details of their ultrastructure are poorly defined. Previously, a novel microwave‐assisted microemulsion‐based technique to prepare SLNs was reported. To understand the detailed internal structure of these SLNs, ultra‐small angle neutron scattering (USANS) and small angle neutron scattering (SANS) experiments are conducted on suspensions of hydrogenated stearic acid SLNs stabilized with hydrogenated Tween 20 surfactant in D2O. Together, SANS and USANS gives a combined Q range of 0.000047 to 0.6 Å−1 (corresponding to a size range of ≈1 nm–15 µm). This extended Q range allows a comprehensive understanding of the hierarchical structure of SLNs. The data are consistent with the multi‐length scale structure of SLNs having polydispersed large particles with roughened surfaces at the microscale level. At the nanoscale level, the results are consistent with the SLNs having an ellipsoidal shape intermediate between spheres and rods, with a crossover from mass fractals to surface fractals. The elucidation of this structure is particularly important given that the structure influences the stability and drug release properties of the nanoparticles. These results assist in the development of systems with desired shape and properties. Neutron scattering techniques are successfully used to probe the hierarchical structure of solid lipid nanoparticles (SLNs). The results indicate multi‐length scale structure of SLNs having polydispersed large particles with roughened surfaces at the microscale level. At the nanoscale level, the SLNs have an ellipsoidal shape intermediate between spheres and rods, with a crossover from mass fractals to surface fractals. [ABSTRACT FROM AUTHOR]

Stearic acid-based solid lipid nanoparticles, stabilised with Tween® 20, were synthesised using a microwave-assisted microemulsion technique and their stability was tested in simulated blood plasma, several liquids mimicking gastrointestinal fluids and solutions containing different electrolyte compositions and pH levels. It was discovered that simulated blood plasma had a stabilising effect on the particles, as did simulated saliva and intestinal fluid, which was due to hydration forces, facilitated by the presence of hydrated cations. It was determined that the hydration stabilisation was pH dependent, with highly acidic conditions depriving the solid lipid nanoparticles of the negative charge required for the cations to hydrate the surface. In environments lacking hydrated cations, the particles were predominately reliant on steric stabilisation and were particularly susceptible to pH extremes due to hydrolysis/oxidation of the Tween® 20 layer. The results suggest that the SLNs have potential as a systemic drug carrier, as the physicochemical conditions of blood provide a stabilising environment that inhibits particle growth. [ABSTRACT FROM AUTHOR]

Tween® 20 stabilised stearic acid solid lipid nanoparticles (SLNs) were prepared using a one-pot microwave-assisted microemulsion technique. Two model water-insoluble drugs, the carboxylic acid-based indomethacin, and the imidazole-based miconazole nitrate, were then used to load the SLNs, and their subsequent physical properties (particle size and zeta potential) were measured and used to predict dispersion stability. Drug-free SLNs had a particle size of 239 nm and a zeta potential of − 29 mV. Indomethacin-loaded SLNs had a particle size of 266 nm and zeta potential of − 30 mV. Miconazole-loaded SLNs had a particle size of 266 nm and zeta potential of + 15 mV. These values were found to be relatively stable (under mildly acidic conditions) and recommend the suitability of the SLNs as a drug carrier. In all cases, the particle size and zeta potential were shown to be pH-dependent. For particle size, a minimum value was obtained at approximately pH 5, which corresponds to the pKa of the lipid used (stearic acid) indicating stearic acid adsorption onto the surface is likely to be at least partly responsible for dispersion stability. We conclude that dispersion stability arises from a combination of electrostatic stability (from adsorbed stearic acid) and limited steric stability from non-ionic (Tween® 20) surface-associated micelles. Dispersions were found to be unstable under alkaline conditions despite the increasingly negative zeta potential of all dispersions. This was observed as an increasingly larger particle size at pH > 7 combined with the observation that particle sizes at pH > 7 were also unstable and continued to increase with time. Visual observations showed dispersions physically broke within a few days at pH values > 7. The encapsulation efficiency (EE) and loading capacity (LC) of drug-loaded SLNs were shown to be close to their theoretical maximum (100%) at low pH, but decreased to < 20%, in the case of indomethacin-loaded SLNs, at a pH >> 7. Interestingly, the EE and LC of miconazole-loaded SLNs when first formed were relatively unaffected by pH. pH control, therefore, is very important to particle stability, and the pH should be kept neutral to mildly acidic. [Display omitted] [ABSTRACT FROM AUTHOR]