Epilobium angustifolium L. Essential Oil-Biological Activity and Enhancement of the Skin Penetration of Drugs-In Vitro Study.

Epilobium angustifolium L. is a popular medicinal plant found in many regions of the world. This plant contains small amounts of essential oil whose composition and properties have not been extensively investigated. There are few reports in the literature on the antioxidant and antifungal properties of this essential oil and the possibility of applying it as a potential promoter of the skin penetration of drugs. The essential oil was obtained by distillation using a Clavenger type apparatus. The chemical composition was analyzed by the GC-MS method. The major active compounds of E. angustifolium L. essential oil (EOEa) were terpenes, including α-caryophyllene oxide, eucalyptol, ß-linalool, camphor, (S)-carvone, and ß-caryophyllene. The analyzed essential oil was also characterized by antioxidant activity amounting to 78% RSA (Radical Scavenging Activity). Antifungal activity against the strains Aspergillus niger, A. ochraceus, A. parasiticum, and Penicillium cyclopium was also determined. The largest inhibition zone was observed for strains from the Aspergillus group. The EOEa enhanced the percutaneous penetration of ibuprofen and lidocaine. After a 24 h test, the content of terpene in the skin and the acceptor fluid was examined. It has been shown that the main compounds contained in the essential oil do not penetrate through the skin, but accumulate in it. Additionally, FTIR-ATR analysis showed a disturbance of the stratum corneum (SC) lipids caused by the essential oil application. Due to its rich composition and high biological activity, EOEa may be a potential candidate to be applied, for example, in the pharmaceutical or cosmetic industries. Moreover, due to the reaction of the essential oil components with SC lipids, the EOEa could be an effective permeation enhancer of topically applied hydrophilic and lipophilic drugs.

Biodegradable Polymeric Nanoparticle-Based Drug Delivery Systems: Comprehensive Overview, Perspectives and Challenges.

In the last few decades, there has been a growing interest in the use of biodegradable polymeric nanoparticles (BPNPs) as the carriers for various therapeutic agents in drug delivery systems. BPNPs have the potential to improve the efficacy of numerous active agents by facilitating targeted delivery to a desired site in the body. Biodegradable polymers are especially promising nanocarriers for therapeutic substances characterized by poor solubility, instability, rapid metabolism, and rapid system elimination. Such molecules can be efficiently encapsulated and subsequently released from nanoparticles, which greatly improves their stability and bioavailability. Biopolymers seem to be the most suitable candidates to be used as the nanocarriers in various delivery platforms, especially due to their biocompatibility and biodegradability. Other unique properties of the polymeric nanocarriers include low cost, flexibility, stability, minimal side effects, low toxicity, good entrapment potential, and long-term and controlled drug release. An overview summarizing the research results from the last years in the field of the successful fabrication of BPNPs loaded with various therapeutic agents is provided. The possible challenges involving nanoparticle stability under physiological conditions and the possibility of scaling up production while maintaining quality, as well as the future possibilities of employing BPNPs, are also reviewed.

Role of Plant Materials with Anti-inflammatory Effects in Phytotherapy of Osteoarthritis.

Osteoarthritis (OA) is a common chronic articular degenerative disease characterized by articular cartilage degradation, synovial inflammation/immunity, and subchondral bone lesions. Recently, increasing interest has been devoted to treating or preventing OA with herbal medicines. The mechanism of action of plant raw materials used in osteoarthrosis treatment is well documented. They are sought after because of the high frequency of inflammation of the knee joint among both elderly and young people engaged in sports in which their knee joints are often exposed to high-stress conditions. The purpose of this work was to present some most effective and safe plant medicines with proven mechanisms of action that can help to alleviate the growing social problem of osteoarthrosis caused in recent years. A review of the available literature based primarily on the latest editions of ESCOP and EMA monographs and the latest scientific papers has made it possible to select and propose medical management of osteoarthrosis by ranking plant medicines according to their effectiveness. Clinical studies of raw plant materials, such as Harpagophyti radix, Olibanum indicum, and Urticae foliumet herba have indicated that these drugs should be considered the first choice in osteoarthrosis treatment. The efficacy of Rosae pseudo-fructus, Salicis cortex, Filipendulae ulmariae flos et herba, Ribis nigri folium, and externally applied Capsici fructus and Symphyti radix, has also been proven by pharmacological studies. All the plant medicines mentioned in the paper have been studied in detail in terms of their phytochemistry, which can help doctors in their decision-- making in the treatment of osteoarthrosis.

Mesoporous Materials as Elements of Modern Drug Delivery Systems for Anti-Inflammatory Agents: A Review of Recent Achievements.

Interest in the use of mesoporous materials as carriers of medicinal substances has been steadily increasing in the last two decades. Mesoporous carriers have application in the preparation of delivery systems for drugs from various therapeutic groups; however, their use as the carriers of anti-inflammatory agents is particularly marked. This review article, with about 170 references, summarizes the achievements in the application of mesoporous materials as the carriers of anti-inflammatory agents in recent years. This article will discuss a variety of mesoporous carriers as well as the characteristics of their porous structure that determine further use of these materials in the field of medical applications. Special attention will be paid to the progress observed in the construction of stimuli-responsive drug carriers and systems providing site-specific drug delivery. Subsequently, a review of the literature devoted to the use of mesoporous matrices as the carriers of anti-inflammatory drugs was carried out.

Modification of the Release of Poorly Soluble Sulindac with the APTES-Modified SBA-15 Mesoporous Silica.

The effectiveness of oral drug administration is related to the solubility of a drug in the gastrointestinal tract and its ability to penetrate the biological membranes. As most new drugs are poorly soluble in water, there is a need to develop novel drug carriers that improve the dissolution rate and increase bioavailability. The aim of this study was to analyze the modification of sulindac release profiles in various pH levels with two APTES ((3-aminopropyl)triethoxysilane)-modified SBA-15 (Santa Barbara Amorphous-15) silicas differing in 3-aminopropyl group content. Furthermore, we investigated the cytotoxicity of the analyzed molecules. The materials were characterized by differential scanning calorimetry, powder X-ray diffraction, scanning and transmission electron microscopy, proton nuclear magnetic resonance and Fourier transformed infrared spectroscopy. Sulindac loaded on the SBA-15 was released in the hydrochloric acidic medium (pH 1.2) and phosphate buffers (pH 5.8, 6.8, and 7.4). The cytotoxicity studies were performed on Caco-2 cell line. The APTES-modified SBA-15 with a lower adsorption capacity towards sulindac released the drug in a less favorable manner. However, both analyzed materials improved the dissolution rate in acidic pH, as compared to crystalline sulindac. Moreover, the SBA-15, both before and after drug adsorption, exhibited insignificant cytotoxicity towards Caco-2 cells. The presented study evidenced that SBA-15 could serve as a non-toxic drug delivery system that enhances the dissolution rate of sulindac and improves its bioavailability.

Sulfonic Acid Derivative-Modified SBA-15, PHTS and MCM-41 Mesoporous Silicas as Carriers for a New Antiplatelet Drug: Ticagrelor Adsorption and Release Studies.

Three mesoporous, siliceous materials, i.e., SBA-15 (Santa Barbara Amorphous), PHTS (Plugged Hexagonal Templated Silica) and MCM-41 (Mobil Composition of Matter), functionalized with a sulfonic acid derivative, were successfully prepared and applied as the carriers for the poorly water-soluble drug, ticagrelor. The siliceous carriers were characterized using nitrogen sorption analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM) and elemental analysis. The adsorption studies were conducted in acetonitrile. At the highest equilibrium concentrations, the amount of ticagrelor Qe that adsorbed onto the examined silicas was in the range of 83 to 220 mg/g, increasing in the following order: PHTS-(CH2)3-SO3H < SBA-15-(CH2)3-SO3H < MCM-41-(CH2)3-SO3H. The equilibrium adsorption data were analyzed using the Freundlich, Jovanovich, Langmuir, Temkin, Dubinin-Radushkevich, Dubinin-Astakhov and Redlich-Peterson models. In order to find the best-fit isotherm for each model, a nonlinear fitting analysis was carried out. Based on the minimized values of the ARE function, the fit of the isotherms to the experimental points for ticagrelor adsorption onto the modified silicas can be ordered as follows: SBA-15-(CH2)3-SO3H (Redlich-Peterson > Dubinin-Astakhov > Temkin), PHTS-(CH2)3-SO3H (Redlich-Peterson > Temkin > Dubinin-Astakhov), MCM-41-(CH2)3-SO3H (Redlich-Peterson > Dubinin-Astakhov > Langmuir). The values of adsorption energy (above 8 kJ/mol) indicate the chemical nature of ticagrelor adsorption onto propyl-sulfonic acid-modified silicas. The results of release studies indicated that at pH 4.5, modified SBA-15 and MCM-41 carriers accelerate the drug dissolution process, compared to the dissolution rate of free crystalline ticagrelor. Intriguingly, modified PHTS silica provides prolonged drug release kinetics compared to other siliceous adsorbents and to the dissolution rate of crystalline ticagrelor. A Weibull release model was employed to describe the release profiles of ticagrelor from the prepared carriers. The time necessary to dissolve 50% and 90% of ticagrelor from mesoporous adsorbents at pH 4.5 increased in the following order: SBA-15-(CH2)3-SO3H < MCM-41-(CH2)3-SO3H < PHTS-(CH2)3-SO3H.

The Effect of SBA-15 Surface Modification on the Process of 18ß-Glycyrrhetinic Acid Adsorption: Modeling of Experimental Adsorption Isotherm Data.

This study aimed at the adsorption of 18ß-glycyrrhetinic acid (18ß-GA), a pentacyclic triterpenoid derivative of oleanane type, onto functionalized mesoporous SBA-15 silica and non-porous silica (Aerosil®) as the reference adsorbent. Although 18ß-GA possesses various beneficial pharmacological properties including antitumor, anti-inflammatory, and antioxidant activity, it occurs is small amounts in plant materials. Thus, the efficient methods of this bioactive compound enrichment from vegetable raw materials are currently studied. Siliceous adsorbents were functionalized while using various alkoxysilane derivatives, such as (3-aminopropyl)trimethoxysilane (APTMS), [3-(methylamino)propyl]trimethoxysilane (MAPTMS), (N,N-dimethylaminopropyl)trimethoxysilane (DMAPTMS), and [3-(2-aminothylamino)propyl] trimethoxysilane (AEAPTMS). The effect of silica surface modification with agents differing in the structure and the order of amine groups on the adsorption capacity of the adsorbent and adsorption efficiency were thoroughly examined. The equilibrium adsorption data were analyzed while using the Langmuir, Freundlich, Redlich-Peterson, Temkin, Dubinin-Radushkevich, and Dubinin-Astakhov isotherms. Both linear regression and nonlinear fitting analysis were employed in order to find the best-fitted model. The adsorption isotherms of 18ß-GA onto silicas functionalized with APTMS, MAPTMS, and AEAPTMS indicate the Langmuir-type adsorption, whereas sorbents modified with DMAPTMS show the constant distribution of the adsorbate between the adsorbent and the solution regardless of silica type. The Dubinin-Astakhov, Dubinin-Radushkevich, and Redlich-Peterson equations described the best the process of 18ß-GA adsorption onto SBA-15 and Aerosil® silicas that were functionalized with APTMS, MAPTMS, and AEAPTMS, regardless of the method that was used for the estimation of isotherm parameters. Based on nonlinear fitting analysis (Dubinin-Astakhov model), it can be concluded that SBA-15 sorbent that was modified with APTMS, MAPTMS, and AEAPTMS is characterized by twice the adsorption capacity (202.8-237.3 mg/g) as compared to functionalized non-porous silica (118.2-144.2 mg/g).

Modeling of boldine alkaloid adsorption onto pure and propyl-sulfonic acid-modified mesoporous silicas. A comparative study.

The present study deals with the adsorption of boldine onto pure and propyl-sulfonic acid-functionalized SBA-15, SBA-16 and mesocellular foam (MCF) materials. Siliceous adsorbents were characterized by nitrogen sorption analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy and thermogravimetric analysis. The equilibrium adsorption data were analyzed using the Langmuir, Freundlich, Redlich-Peterson, and Temkin isotherms. Moreover, the Dubinin-Radushkevich and Dubinin-Astakhov isotherm models based on the Polanyi adsorption potential were employed. The latter was calculated using two alternative formulas including solubility-normalized (S-model) and empirical C-model. In order to find the best-fit isotherm, both linear regression and nonlinear fitting analysis were carried out. The Dubinin-Astakhov (S-model) isotherm revealed the best fit to the experimental points for adsorption of boldine onto pure mesoporous materials using both linear and nonlinear fitting analysis. Meanwhile, the process of boldine sorption onto modified silicas was described the best by the Langmuir and Temkin isotherms using linear regression and nonlinear fitting analysis, respectively. The values of adsorption energy (below 8kJ/mol) indicate the physical nature of boldine adsorption onto unmodified silicas whereas the ionic interactions seem to be the main force of alkaloid adsorption onto functionalized sorbents (energy of adsorption above 8kJ/mol).

Amine-modified SBA-15 and MCF mesoporous molecular sieves as promising sorbents for natural antioxidant. Modeling of caffeic acid adsorption.

This work presents a detailed study of caffeic acid adsorption on mesoporous SBA-15 and MCF silicas functionalized with (3-aminopropyl)triethoxysilane (APTES) and 3-[2-(aminoethylamino)propyl]trimethoxysilane (AEAPTMS). Synthesized mesoporous adsorbents were characterized using different analytical techniques such as N2 sorption, XRD, TEM, SEM and FT-IR. The adsorption studies of caffeic acid were conducted in various organic solvents. Moreover, the effect of water content in 2-propanol-water mixture on adsorption efficiency was investigated. The experimental data were best fitted to the Langmuir equation, followed by the Temkin, Dubinin-Radushkevich and Freundlich models. The maximum adsorption capacity values calculated from the Langmuir model demonstrated that SBA-15 and MCF silicas modified with AEAPTMS revealed better adsorption properties toward caffeic acid (192.3 and 161.3mg/g, respectively) as compared to the materials modified with APTES (125.0 and 113.6 mg/g, respectively). The obtained results indicate that both SBA-15 and MCF silicas functionalized with AEAPTMS and APTES are promising materials for the entrapment of caffeic acid.

Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems.

Recent Developments in the Application of Polymeric Nanoparticles as Drug Carriers.

Nanotechnology is an interdisciplinary field of science offering interesting solutions for many branches of human life. Nanomaterials, defined as structures with at least one dimension below 100 nm, are the focus of increasing research attention as versatile tools for nanomedicine. Among the various nanostructures recently described in the literature, polymeric nanoparticles, characterized by satisfying biocompatibility, have aroused great interest as the carriers for various biologically active substances such as drugs, proteins and nucleic acids. These nanoparticles have already been reported as efficient vehicles for therapeutic agents in many disease entities. They can be delivered to the body via different administration routes. This review addresses recent advances in the usage of polymeric nanoparticles as drug carriers described in the years 2013 and 2014. The advantages of polymeric nanocarriers for medical application are highlighted, including their low toxicity, evaluated in vitro and in vivo. Moreover, the classification of polymeric nanoparticles is presented as well as various protocols of their synthesis.

Mesoporous materials as multifunctional tools in biosciences: principles and applications.

Research on mesoporous materials for biomedical and biological applications has experienced an outstanding increase during recent years. This review with ca. 420 references provides an overview of mesoporous structures covering synthesis and bioapplications. Various methods of mesoporous material preparation and modification are discussed as controlled synthesis of these molecular sieves has great impact on their properties and applications. In the area of bioapplications, mesoporous materials offer the potential for drug delivery, bioimaging, regenerative medicine, optical and electrochemical biosensing, enzyme immobilization, biomolecule sorption and separation and many others. We also discuss the cytotoxicity aspects of mesoporous structures being of crucial importance for successful application of these novel tools in the biomedical field. Future prospects of mesoporous materials have been also briefly discussed. We believe that the present review will serve as a comprehensive guide for scientists in the area of biosciences giving the background in regard to mesoporous materials.

Application of nanoporous silicas as adsorbents for chlorinated aromatic compounds. A comparative study.

The removal of two selected environmental pollutants such as 2,4-dichlorophenoxyacetic acid (2,4-D) and Triclosan (TC) was examined by adsorption experiments on the modified SBA-15 and MCF mesoporous silicas. Mesoporous adsorbents were modified by a grafting process with (3-aminopropyl)triethoxysilane (APTES) and 1-[3-(trimethoxysilyl)propyl]urea (TMSPU). Mesoporous materials were synthesized and characterized by N2 adsorption-desorption experiment, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), elemental analysis and adsorption studies. The results show that both APTES-functionalized SBA-15 and MCF nanoporous carriers are potentially good adsorbents for the removal of 2,4-D in a wide range of concentrations from 0.1 to 4 mg/cm(3). Maximum adsorption capacity of as-modified adsorbents for 2,4-D estimated from the Langmuir model was ~280 mg/g. The ionic interaction between the adsorbent and 2,4-D seems to play a key role in the adsorption process of the pollutant on APTES-modified siliceous matrices. The efficiency of TC sorption onto all prepared mesoporous adsorbents was significantly lower as compared to the entrapment of 2,4-D. Experimental data were best fitted by the Langmuir isotherm model. The results of this study suggest that mesoporous silica-based materials are promising adsorbents for the removal of selected organic pollutants.

Quantum dots as versatile probes in medical sciences: synthesis, modification and properties.

Quantum dots (QDs) are semiconductor inorganic fluorescent nanocrystals in the size range between 1 and 20 nm. Due to their very small size, they possess unique properties and behave in different way than crystals in macro scale. The specificity of QDs makes them widespread in many branches of human life. The disciplines that took recently huge advantage from the development of nanotechnology are medicine and pharmacy. The creation of particles of very tiny sizes allowed these two sciences to develop or revolutionize the techniques of diagnosis or drug delivery. The most important feature for application of fluorescent nanocrystals in medical and pharmaceutical sciences is their high surface to volume ratio enabling QDs' conjugation to multiple ligands. Other properties of great importance are dispersibility and water stability, high and not easy quenched fluorescence, biocompatibility, and small and uniform sizes. In this review with ca. 200 references the recent developments in QD synthesis, surface modification, QD-based bioimaging, biotracking of drug molecules, biosensing and photodynamic therapy are summarized.

Thioglycerol-capped Mn-doped ZnS quantum dot bioconjugates as efficient two-photon fluorescent nano-probes for bioimaging.

Water-dispersible 1-thioglycerol (TG)-capped Mn-doped ZnS quantum dots were prepared in aqueous solution using the nucleation-doping strategy. Using 4% Mn relative to Zn and a Zn(OAc)2/Na2S ratio of 0.9, Mn:ZnS nanocrystals with an average diameter of 3.9 ± 0.5 nm, with pure Mn2+-related photoluminescence (PL) at 585 nm, and with a PL quantum yield of 13.2% were obtained. Transmission electron microscopy, X-ray powder diffraction, electron spin resonance, X-ray photoelectron spectroscopy, UV-visible spectroscopy and spectrofluorometry have been used to characterize the crystal structure, the doping status, and the optical properties of the doped-dots. Folic acid (FA) was linked to TG-capped Mn:ZnS nanocrystals to produce Mn:ZnS@TG-FA nanobioconjugates that were used for targeted in vitro delivery to a human cancer cell line. Folate receptor mediated cellular uptake of FA-functionalized dots is proven via confocal and two-photon imaging.

Folic acid-conjugated core/shell ZnS:Mn/ZnS quantum dots as targeted probes for two photon fluorescence imaging of cancer cells.

This work presents a novel approach to producing water soluble manganese-doped core/shell ZnS/ZnS quantum dots (ZnS:Mn/ZnS). The Mn-doped ZnS core was prepared through a nucleation doping strategy and a ZnS shell was grown on ZnS:Mn d-dots by decomposition of Zn(2+)-3-mercaptopropionic acid (MPA) complexes at 100 °C. It was found that the Mn2+(4)T1→6A1 fluorescence emission at ∼590 nm significantly increased after growth of the shell when the Mn2+ doping content was 4.0 at.%. A photoluminescence quantum yield of ∼22% was obtained for core/shell nanocrystals. The nanoparticles were structurally and compositionally characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and dynamic light scattering. The surface MPA molecules favor the dispersion of ZnS:Mn/ZnS QDs in aqueous media and make possible conjugation with targeting folic acid molecules. The folate receptor-mediated delivery of folic acid-conjugated ZnS:Mn/ZnS QDs was demonstrated using confocal microscopy with biphotonic excitation. Bare and folate-conjugated QDs exhibit only weak cytotoxicity towards folate receptor-positive T47D cancer cells and MCF-7 cells, used as a reference, at high concentrations (mmolar range) after 72h incubation.