Development of End-Spliced Dimeric Nanodiscs for the Improved Virucidal Activity of a Nanoperforator.

Lipid-bilayer nanodiscs (NDs) wrapped in membrane scaffold proteins (MSPs) have primarily been used to study membrane proteins of interest in a physiological environment. Recently, NDs have been employed in broader applications including drug delivery, cancer immunotherapy, bio-imaging, and therapeutic virucides. Here, we developed a method to synthesize a dimeric nanodisc, whose MSPs are circularly end-spliced, with long-term thermal stability and resistance to aggregation. The end-spliced nanodiscs (esNDs) were assembled using MSPs that were self-circularized inside the cytoplasm ofEscherichia colivia highly efficient protein trans-splicing. The esNDs demonstrated a consistent size and 4-5-fold higher stability against heat and aggregation than conventional NDs. Moreover, cysteine residues on trans-spliced circularized MSPs allowed us to modulate the formation of either monomeric nanodiscs (essNDs) or dimeric nanodiscs (esdNDs) by controlling the oxidation/reduction conditions and lipid-to-protein ratios. When the esdNDs were used to prepare an antiviral nanoperforator that induced the disruption of the viral membrane upon contact, antiviral activity was dramatically increased, suggesting that the dimerization of nanodiscs led to cooperativity between linked nanodiscs. We expect that controllable structures, long-term stability, and aggregation resistance of esNDs will aid the development of novel versatile membrane-mimetic nanomaterials with flexible designs and improved therapeutic efficacy.

Specific Uptake of Lipid-Antibody-Functionalized LbL Microcarriers by Cells.

The modular construction of Layer-by-Layer biopolymer microcarriers facilitates a highly specific design of drug delivery systems. A supported lipid bilayer (SLB) contributes to biocompatibility and protection of sensitive active agents. The addition of a lipid anchor equipped with PEG (shielding from opsonins) and biotin (attachment of exchangeable outer functional molecules) enhances the microcarrier functionality even more. However, a homogeneously assembled supported lipid bilayer is a prerequisite for a specific binding of functional components. Our investigations show that a tightly packed SLB improves the efficiency of functional components attached to the microcarrier's surface, as illustrated with specific antibodies in cellular application. Only a low quantity of antibodies is needed to obtain improved cellular uptake rates independent from cell type as compared to an antibody-functionalized loosely packed lipid bilayer or directly assembled antibody onto the multilayer. A fast disassembly of the lipid bilayer within endolysosomes exposing the underlying drug delivering multilayer structure demonstrates the suitability of LbL-microcarriers as a multifunctional drug delivery system.

Recent advances in liposome surface modification for oral drug delivery.

Oral delivery via the gastrointestinal (GI) tract is the dominant route for drug administration. Orally delivered liposomal carriers can enhance drug solubility and protect the encapsulated theraputic agents from the extreme conditions found in the GI tract. Liposomes, with their fluid lipid bilayer membrane and their nanoscale size, can significantly improve oral absorption. Unfortunately, the clinical applications of conventional liposomes have been hindered due to their poor stability and availability under the harsh conditions typically presented in the GI tract. To overcome this problem, the surface modification of liposomes has been investigated. Although liposome surface modification has been extensively studied for oral drug delivery, no review exists so far that adequately covers this topic. The purpose of this paper is to summarize and critically analyze emerging trends in liposome surface modification for oral drug delivery.

Bicelles: New Lipid Nanosystems for Dermatological Applications.

Bicelles have emerged as promising membrane models, and due to their attractive combination of lipid composition and physicochemical characteristics, they have become new nanostructures for biomedical research. Depending on the composition, temperature and other experimental factors, these nanosystems exhibit high structural and morphological versatility. Additionally, bicelles are able to modulate the biophysical parameters and barrier function of skin. Given these properties, these nanostructures appear to be smart nanosystems with great potential in biomedicine and dermopharmacy.

RP-HPLC method for simultaneous estimation of atorvastatin calcium and ramipril from plasma

Solid lipid microparticles (SLMs) loaded with ketoprofen were prepared by single emulsion-solvent evaporation method, in which glyceryl monostearate and Tween 80 were employed. The particle size was found to be 99.80±2.1μm. Microparticles observed by scanning electron microscope (SEM) showed spherical shape. The entrapment efficiency (EE %) and drug loading capacity (DL %) were found to be 72.60±1.6 % and 17.98±0.7% respectively. Results of stability evaluation showed relatively long term stability after storage at 4˚C for 3 months. The in-vivo study revealed slightly better per cent inhibition of pain i.e. 74% in comparison with 68% produced by plain drug(AU)

Las micropartículas lipídicas sólidas (MLS) cargadas con ketoprofeno se prepararon a través del método de evaporación del disolvente en emulsión simple, en el que se ha utilizado monoestearato de glicerilo y Tween 80. El tamaño de la partícula resultó ser de 99,80±2,1 μm. Las micropartículas observadas a través del microscopio electrónico de barrido (MEB) mostraron una forma esférica. La eficacia de captura (EC %) y la capacidad de carga (CC %) del fármaco resultaron ser del 72,60±1,6% y 17,98±0,7%, respectivamente. Los resultados de la evaluación de estabilidad mostraron una estabilidad relativa a largo plazo, después de una conservación a 4˚C durante 3 meses. El estudio in vivo reveló un ligero mejor porcentaje en la inhibición del dolor, concretamente, un 74% en comparación con un 68% producido por un fármaco corriente(AU)

[Liposomes as drug carrier systems. Preparation, classification and therapeutic advantages of liposomes]. / A liposzóma mint gyógyszerszállító rendszer. A liposzómák elóállítása, alapvetó típusaik és terápiás alkalmazásuk elónyei.

Bangham et al. (1965) created first the concept of the liposome as a microparticulate lipoidal vesicle separated from its aqueous environment by one or more lipid bilayers. Later Gregoriadis and Ryman (1972) suggested to use liposomes as drug carrier systems. Nowadays liposomes are under extensive investigation for improving the delivery of therapeutic agents, enzymes, vaccines and genetic materials. Liposomes offer an excellent opportunity to selective targeting of drugs which is expected to optimize the pharmacokinetical parameters, the pharmacological effect and to reduce the toxicity of the encapsulated drugs. To understand the system it is important to know the basic properties of these lipoidal vesicles. Our aim was to focus on the lipid composition and the method of liposome preparation what determine the liposomal membrane fluidity, permeability, vesicle size, charge density, steric hindrance and stability of the liposomes as principle factors those influence the fate of liposomes, their interactions with the blood components and other tissues after systemic administration or local use.