Rohan M. Shah

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.

Pharmacological properties of guggulsterones, the major active components of gum guggul.

Oleo gum resin secreted by Commiphora mukul, also known as gum guggul, has been used widely as an ayurvedic drug. Commiphora mukul is a short thorny shrub that is native to the Indian subcontinent. Oleo gum resin extracted by incision of the bark is a very complex mixture of gum, minerals, essential oils, terpenes, sterols, ferrulates, flavanones and sterones. Its active constituents, the Z‐ and E‐guggulsterones, have been demonstrated to exhibit their biological activities by binding to nuclear receptors and modulating the expression of proteins involved in carcinogenic activities. Guggulsterones have also been reported to regulate gene expression by exhibiting control over other molecular targets including transcription factors such as nuclear factor (NF)‐κB, signal transducer and activator of transcription (STAT) and steroid receptors. Considerable scientific evidence indicates the use of gum guggul as a therapeutic agent in the treatment of inflammation, nervous disorders, hyperlipidaemia and associated cardiac disorders such as hypertension and ischaemia, skin disorders, cancer and urinary disorders. This review highlights the taxonomic details, phytochemical properties and pharmacological profile of gum guggul. Copyright

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.

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.