There is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures. As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.

• MeSH
• farmaceutická chemie metody   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• kyseliny laurové chemie   MeSH
• lipidy * chemie   MeSH
• oleje chemie   MeSH
• polysorbáty chemie   MeSH
• povrchově aktivní látky * chemie   MeSH
• příprava léků * metody   MeSH
• rozpouštědla * chemie   MeSH
• rozpustnost * MeSH
• simulace molekulární dynamiky * MeSH
• sulfonamidy chemie   aplikace a dávkování   MeSH
• uvolňování léčiv * MeSH
• Publikační typ
• časopisecké články MeSH

With an increasing number of lipophilic drugs under development, homolipids and heterolipids have gained renewed interests as excipients for oral drug delivery systems. Oral administration has many advantages for chronic drug therapy. It is relatively safe, convenient for the patient and allows self administration. This article is not intended to review the broad area of lipid-based vehicle for oral drug delivery comprehensively. The rationale behind choosing lipids materials for pharmaceutical dosage forms and their applications is discussed. It also comments on the methods for monitoring the physicochemical properties of vehicles and formulations and describes a range of pharmacopoeial excipients suitable for these purposes. The excipients selected here are pharmacopoeial in European Pharmacopoeia 4th Ed., United States Pharmacopoeia 24th Ed./National Formulary 19th Ed. and Japanese Pharmacopoeia 13th Ed. or are drafted in Pharmaeuropa and Pharmacopoeial Forum. Widening availability of lipidic excipients with specific characteristics offer flexibility of application with respect to improving the bioavailability of poorly water-soluble drugs and manipulating release profiles.

• MeSH
• aplikace orální MeSH
• farmaceutická vehikula * MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• lipidy * MeSH
• pomocné látky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

alpha-Tocopheryl succinate (alpha-TOS) is a semisynthetic analogue of alpha-tocopherol with selective toxicity to the cancer cells and anticancer activity in vivo. Yet, no suitable formulation of alpha-TOS for medical application has been reported. Various formulations, for example, solutions in organic solvents, oil emulsions and vesicules prepared by spontaneous vesiculation, polyethylene glycol conjugates and liposomes of various compositions have been tested. We developed and characterised a stable lyophilised liposome-based alpha-TOS formulation. alpha-TOS (15 mol%) was incorporated into large oligolamellar vesicles (OLVs) composed of soy phosphatidylcholine (SPC) by the method of lipid film hydration followed by extrusion through polycarbonate filters. Stabilised liposomal formulation was prepared by lyophilisation in the presence of sucrose (molar ratio lipid/sucrose, 1:5). The size distribution of the liposomes (130-140 nm, polydispersity index 0.14) as well as the stable lipid and alpha-TOS contents were preserved during storage in the lyophilised form at 2-8 degrees C for at least 6 months. The data indicate good physical and chemical stability of the lyophilised preparation of alpha-TOS liposomes that can be used in clinical medicine.

• MeSH
• alfa-tokoferol aplikace a dávkování   chemie   MeSH
• lipidy chemie   MeSH
• liposomy MeSH
• lyofilizace MeSH
• lysofosfolipidy chemie   MeSH
• peroxid vodíku chemie   MeSH
• povrchové vlastnosti MeSH
• příprava léků metody   MeSH
• protinádorové látky aplikace a dávkování   chemie   MeSH
• skladování léků MeSH
• stabilita léku MeSH
• transmisní elektronová mikroskopie MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The use of natural compounds is becoming increasingly popular among patients, and there is a renewed interest among scientists in nature-based bioactive agents. Traditionally, herbal drugs can be taken directly in the form of teas/decoctions/infusions or as standardized extracts. However, the disadvantages of natural compounds, especially essential oils, are their instability, limited bioavailability, volatility, and often irritant/allergenic potential. However, these active substances can be stabilized by encapsulation and administered in the form of nanoparticles. This brief overview summarizes the latest results of the application of nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers used as drug delivery systems of herbal essential oils or used directly for their individual secondary metabolites applicable in cancer therapy. Although the discussed bioactive agents are not typical compounds used as anticancer agents, after inclusion into the aforesaid formulations improving their stability and bioavailability and/or therapeutic profile, they indicated anti-tumor activity and became interesting agents with cancer treatment potential. In addition, co-encapsulation of essential oils with synthetic anticancer drugs into nanoformulations with the aim to achieve synergistic effect in chemotherapy is discussed.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The aim of this study was to follow the skin penetration of a model lipophilic compound (Nile red) delivered by nanoparticulate carriers, the so-called lipid nanocapsules. The nanocapsules consisting of an oil core stabilized by amixture of surfactants were prepared by the phase inversion temperature method. Varying the particle composition (the oil/surfactant ratio) nanoparticles of different size were prepared and characterized. The penetration profile of Nile red delivered into the porcine skin by the nanoparticles compared to non-particulate samples was determined using fluorescence microscopy combined with a novel, statistically robust quantitative image analysis method. This study demonstrated that lipid nanoparticles promoted the skin penetration of encapsulated Nile red in comparison with all the non-particulate samples. Nile red delivered by the lipid-based nanoparticles was able to diffuse across the stratum corneum and partition itself uniformly in the epidermis. No relationship between Nile red penetration into the skin and the particle size was found. Moreover, the presence of sodium chloride in the water phase had a negative impact on the Nile red penetration into the skin. The results indicate that the physico-chemical circumstances of the nanoparticulate formulation play the major role in the penetration of lipophilic substances into the skin.

• MeSH
• epidermis účinky léků   MeSH
• fluorescenční mikroskopie MeSH
• konfokální mikroskopie MeSH
• kožní absorpce MeSH
• kůže účinky léků   patologie   MeSH
• lékové transportní systémy MeSH
• lipidy chemie   MeSH
• nanočástice chemie   MeSH
• nanokapsle chemie   MeSH
• nosiče léků chemie   MeSH
• oleje chemie   MeSH
• oxaziny chemie   MeSH
• počítačové zpracování obrazu MeSH
• povrchově aktivní látky chemie   MeSH
• prasata MeSH
• software MeSH
• transmisní elektronová mikroskopie MeSH
• velikost částic MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Despite the increasing interest in pharmaceutical use of mesoporous silica, there is still only limited knowledge on mechanisms of pore loading and subsequent drug desorption and release. Hence the aim of this work was to address the mechanistic aspects of drug loading into the mesoporous silica pores and to minimise the risk of pore clogging. Hydrophilic solvents (polysorbate 20 and polyethylene glycol 200) with high dissolving capacity for the model drug celecoxib were studied for their surface tension as well as dynamic viscosity by considering hydration. As an innovation in liquisolid systems preparation, a rather simple drug loading method on a mesoporous carrier was introduced by using semi-volatile solvent mixtures. Fast liquid loading into the pores was achieved due to the lowered viscosity and surface tension of the whole solvent system. Drug release kinetics suggested that lipid-based formulations belonging to class IV of Lipid Formulation Classification System may exhibit a lower risk of incomplete desorption from a carrier. The utilisation of volatile solvents during preparation had no negative impact on the liquisolid systems' dissolution behaviour. All prepared formulations showed similar significantly faster dissolution profiles compared to the physical mixture. The novel approach has potential to promote liquisolid applications in pharmaceutics.

• MeSH
• diferenciální skenovací kalorimetrie metody   MeSH
• farmaceutická chemie metody   MeSH
• farmaceutická technologie metody   MeSH
• hydrofobní a hydrofilní interakce MeSH
• kinetika MeSH
• léčivé přípravky chemie   MeSH
• lipidy chemie   MeSH
• nosiče léků chemie   MeSH
• oxid křemičitý chemie   MeSH
• polysorbáty chemie   MeSH
• propylenglykol chemie   MeSH
• rozpouštědla chemie   MeSH
• rozpustnost účinky léků   MeSH
• tablety chemie   MeSH
• Publikační typ
• časopisecké články MeSH

We developed fully biodegradable/metabolizable nanosystem based on polymer surfactant-stabilized thermoresponsive solid lipid nanoparticles with non-covalently bound photosensitizer temoporfin (T-SLNP) with particle size below 50nm. The efficacy of T-SLNP was compared with commercial temoporfin formulation in terms of in vitro phototoxicity in 4T1 (murine mammary carcinoma) and MDA-MB-231(human breast adenocarcinoma) cells and of in vivo anticancer effect in Nu/Nu mice bearing MDA-MB-231 tumors. In vitro study demonstrated faster accumulation kinetics in the cells for our formulation design resulting in higher phototoxicity against the tumor cells. In vivo anticancer efficacy was markedly improved by T-SLNP compared with commercial temoporfin formulation. Owing to controlled and sustained release properties, subcellular size, biocompatibility with tissue and cells, the T-SLNP nanodispersion prepared in this study represents promising drug delivery system applicable in cancer treatment.

• MeSH
• experimentální nádory mléčných žláz terapie   MeSH
• fotochemoterapie metody   MeSH
• fotosenzibilizující látky aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• lipidy chemie   MeSH
• mastné alkoholy aplikace a dávkování   terapeutické užití   MeSH
• mesoporfyriny chemie   MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanočástice chemie   MeSH
• nosiče léků chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The present work highlights recent achievements in development of nanostructured dispersions and biocolloids for drug delivery applications. We emphasize the key role of biological small-angle X-ray scattering (BioSAXS) investigations for the nanomedicine design. A focus is given on controlled encapsulation of small molecular weight phytochemical drugs in lipid-based nanocarriers as well as on encapsulation of macromolecular siRNA, plasmid DNA, peptide and protein pharmaceuticals in nanostructured nanoparticles that may provide efficient intracellular delivery and triggered drug release. Selected examples of utilisation of the BioSAXS method for characterization of various types of liquid crystalline nanoorganizations (liposome, spongosome, cubosome, hexosome, and nanostructured lipid carriers) are discussed in view of the successful encapsulation and protection of phytochemicals and therapeutic biomolecules in the hydrophobic or the hydrophilic compartments of the nanocarriers. We conclude that the structural design of the nanoparticulate carriers is of crucial importance for the therapeutic outcome and the triggered drug release from biocolloids.

• MeSH
• difrakce rentgenového záření MeSH
• fytonutrienty chemie   farmakologie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• koloidy MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• maloúhlový rozptyl MeSH
• nanočástice chemie   MeSH
• nosiče léků * MeSH
• peptidy chemie   metabolismus   MeSH
• plazmidy chemie   metabolismus   MeSH
• příprava léků metody   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Disrupted skin barrier, one of the severe attributes of inflammatory skin diseases, is caused by lower content and pathological changes of lipids in the uppermost skin layer-stratum corneum (SC). Restoring skin barrier with native skin lipids, especially ceramides (Cers), appears to be a promising therapy with minimum side effects. For testing the efficiency of these formulations, suitable in vitro models of the skin with disrupted barriers are needed. For the similarity with the human tissue, our models were based on the pig ear skin. Three different ways of skin barrier disruption were tested and compared: tape stripping, lipid extraction with organic solvents, and barrier disruption by sodium lauryl sulfate. The level of barrier disruption was investigated by permeation studies, and parameters of each method were modified to reach significant changes between the non-disrupted skin and our model. Fourier transform infrared (FTIR) spectroscopy was employed to elucidate the changes of the skin permeability on the molecular scale. Further, the potential of the developed models to be restored by skin barrier repairing agents was evaluated by the same techniques. We observed a significant decrease in permeation characteristics through our in vitro models treated with the lipid mixtures compared to the untreated damaged skin, which implied that the skin barrier was substantially restored. Taken together, the results suggest that our in vitro models are suitable for the screening of potential barrier repairing agents.

• MeSH
• ceramidy * MeSH
• epidermis MeSH
• kůže * MeSH
• lipidy MeSH
• permeabilita MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To provide a comprehensive and up-to-date overview focusing on the extent of lymphatic transport of drugs following intestinal absorption and to summarize available data on the impact of molecular weight, lipophilicity, formulation and prandial state. METHODS: Literature was searched for in vivo studies quantifying extent of lymphatic transport of drugs after enteral dosing. Pharmacokinetic data were extracted and summarized. Influence of molecular weight, log P, formulation and prandial state was analyzed using relative bioavailability via lymph (FRL) as the parameter for comparison. The methods and animal models used in the studies were also summarized. RESULTS: Pharmacokinetic data on lymphatic transport were available for 103 drugs. Significantly higher FRL [median (IQR)] was observed in advanced lipid based formulations [54.4% (52.0)] and oil solutions [38.9% (60.8)] compared to simple formulations [2.0% (27.1)], p < 0.0001 and p = 0.004, respectively. Advanced lipid based formulations also provided substantial FRL in drugs with log P < 5, which was not observed in simple formulations and oil solutions. No relation was found between FRL and molecular weight. There were 10 distinct methods used for in vivo testing of lymphatic transport after intestinal absorption so far. CONCLUSION: Advanced lipid based formulations provide superior ability to increase lymphatic absorption in drugs of various molecular weights and in drugs with moderate to low lipophilicity.

• MeSH
• aplikace orální MeSH
• biologická dostupnost MeSH
• biologický transport fyziologie   MeSH
• databáze bibliografické MeSH
• farmakokinetika MeSH
• intestinální absorpce MeSH
• léčivé přípravky MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• lymfatický systém metabolismus   MeSH
• modely u zvířat MeSH
• příprava léků metody   statistika a číselné údaje   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH