Hypericin supramolecular assembles: A way to increase the skin availability and photodynamic efficiency in tumor cells.

Cyclodextrins (CDs) are molecules approved by the FDA and show promise in increasing the solubility of hydrophobic molecules and making them more available to the skin. These CDs have been used to form complexes with some photosensitizers for Photodynamic Therapy (PDT), such as Hypericin (HY). HY is a lipophilic photosensitizer known for its exceptional fluorescence and singlet oxygen quantum yield generation of over 20 % under 590 nm irradiation. In this study, we found a six-fold increase in the release of HY in vitro after complexation with ß-CD. The ß-CDHY assembly also demonstrated better skin retention, which is crucial for the topical application of this photosensitizer. Furthermore, the ß-CD complexation led to a significant increase in the phototoxicity of HY at three different light doses (3, 6, and 10 J cm-2) due to its improved water solubility and higher in vitro accumulation (approximately two times compared with free HY) in HeLa and Vero cell lines.

Design and Characterization of Lipid-Surfactant-Based Systems for Enhancing Topical Anti-Inflammatory Activity of Ursolic Acid.

Skin inflammation is a symptom of many skin diseases, such as eczema, psoriasis, and dermatitis, which cause rashes, redness, heat, or blistering. The use of natural products with anti-inflammatory properties has gained importance in treating these symptoms. Ursolic acid (UA), a promising natural compound that is used to treat skin diseases, exhibits low aqueous solubility, resulting in poor absorption and low bioavailability. Designing topical formulations focuses on providing adequate delivery via application to the skin surface. The aim of this study was to formulate and characterize lipid-surfactant-based systems for the delivery of UA. Microemulsions and liquid crystalline systems (LCs) were characterized by polarized light microscopy (PLM), rheology techniques, and textural and bioadhesive assays. PLM supported the self-assembly of these systems and elucidated their formation. Rheologic examination revealed pseudoplastic and thixotropic behavior appropriate, and assays confirmed the ability of these formulations to adhere to the skin. In vivo studies were performed, and inflammation induced by croton oil was assessed for response to microemulsions and LCs. UA anti-inflammatory activities of ~60% and 50% were demonstrated by two microemulsions and 40% and 35% by two LCs, respectively. These data support the continued development of colloidal systems to deliver UA to ameliorate skin inflammation.

PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement of ursolic acid release

Abstract Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA.

Reversed-phase high-performance liquid chromatography: A fast and efficient analytical method to quantify docetaxel-loaded pegylated liposomes in release study.

Docetaxel is an anticancer that belongs to the family of taxanes and acts in the inhibition of cell proliferation through the polymerization of microtubules. The aim of this study was the development and validation of a fast method by reversed-phase high-performance liquid chromatography for quantitative analysis of docetaxel encapsulated in pegylated liposomes. The analytical method was validated for the following recognized specifications: system suitability, precision (repeatability and intermediate precision), linearity, accuracy, selectivity, detection and quantification limits, and robustness. The reversed phase-high-performance liquid chromatography analyses were performed at a temperature of 45°C (isocratic mode). The mobile phase was composed of acetonitrile and water (65:35, v/v) and the flow rate was fixed at 0.8 mL/min. The running time and wavelength were 8 min and 230 nm, respectively. The method was found to be linear, precise, selective, precise, robust, accurate, in the range of 1-75 µg/mL (R2 = 0.9999) and the values of detection and quantification limits were 2.35 and 7.84 µg/mL, respectively. The release rates of docetaxel in pegylated liposomes were lower compared to docetaxel in solution. The reversed phase high-performance liquid chromatography method developed proved to be adequate and can be effectively used to determine the in vitro release profile of docetaxel transported by pegylated liposomes.

Highlights Regarding the Use of Metallic Nanoparticles against Pathogens Considered a Priority by the World Health Organization.

The indiscriminate use of antibiotics has facilitated the growing resistance of bacteria, and this has become a serious public health problem worldwide. Several microorganisms are still resistant to multiple antibiotics and are particularly dangerous in the hospital and nursing home environment, and to patients whose care requires devices, such as ventilators and intravenous catheters. A list of twelve pathogenic genera, which especially included bacteria that were not affected by different antibiotics, was released by the World Health Organization (WHO) in 2017, and the research and development of new antibiotics against these genera has been considered a priority. The nanotechnology is a tool that offers an effective platform for altering the physicalchemical properties of different materials, thereby enabling the development of several biomedical applications. Owing to their large surface area and high reactivity, metallic particles on the nanometric scale have remarkable physical, chemical, and biological properties. Nanoparticles with sizes between 1 and 100 nm have several applications, mainly as new antimicrobial agents for the control of microorganisms. In the present review, more than 200 reports of various metallic nanoparticles, especially those containing copper, gold, platinum, silver, titanium, and zinc were analyzed with regard to their anti-bacterial activity. However, of these 200 studies, only 42 reported about trials conducted against the resistant bacteria considered a priority by the WHO. All studies are in the initial stage, and none are in the clinical phase of research.

Synthesis and characterization of meloxicam eutectics with mandelic acid and saccharin for enhanced solubility.

Meloxicam (MLX) is a non-steroidal anti-inflammatory which is practically insoluble in water, requiring high concentrations to reach therapeutic levels and causing frequently gastrointestinal effects. In this way, the aim of this study was to synthesize two eutectic mixtures of MLX with mandelic acid (MND) and saccharin (SAC) by liquid-assisted grinding resulting in a multicomponent material with enhanced solubility. Mixtures were studied in different stoichiometric and eutectic point was found for each eutectic by Binary phase diagram and Tamman's triangle, with 0.33 molar fraction of MLX for SAC and MND. Eutectics were characterized by thermoanalytical techniques (TG-DSC, EGA, DSC, and DSC microscopy), infrared spectroscopy, and X-ray powder diffraction. Thermal behavior was studied and videos of the materials being heated were available. A polymorphic transition was discovered and studied for MLX-MND eutectic. Each new system was evaluated by solubility, dissolution, and hygroscopicity tests. Eutectics showed an increase in solubility of 1.7× (MLX-MND1), 3.1× (MLX-MND2), and 1.3× (MLX-SAC) with slower dissolution profile when compared with MLX. All new solid forms showed high hygroscopicity at 98% relative humidity with 27.9 and 58.9% increase in mass at day four for MLX-SAC and MLX-MND, deliquescence occurs at day 6. The experiments and analysis in this study help to understand the behavior of eutectics and evaluate them as an approach to modify properties in drugs.

Recent Advances in the Use of Metallic Nanoparticles with Antitumoral Action - Review.

The term cancer represents a set of more than 100 diseases that are caused due to an uncontrolled growth of cells; and their subsequent spread to the other tissues and organs of the body by a phenomenon, called 'metastasis'. According to the estimates provided by the World Health Organization (WHO), cancer is expected to account for about 10 million deaths per year by 2020 and 21 million cancer cases, which may lead to 13 million deaths by 2030, making cancer as the cause of highest mortality in contrast to other diseases. The search for potential therapeutics against cancer, which can reduce the side-effects that occur due to the difficulty of recognition between cancerous and normal cells, has ever been increased. In this view, nanotechnology, especially metallic nanoparticles (MNPs), comes to aid in the development of novel therapeutic agents, which may be synthesized or modified with the most diverse functional chemical groups; this property makes the metallic nanoparticles suitable for conjugation with already known drugs or prospective drug candidates. The biocompatibility, relatively simple synthesis, size flexibility and easy chemical modification of its surface, all make the metallic nanoparticles highly advantageous for opportune diagnosis and therapy of cancer. The present article analyzes and reports the anti-tumor activities of 78 papers of various metallic nanoparticles, particularly the ones containing copper, gold, iron, silver and titanium in their composition.

Characteristics, Biological Properties and Analytical Methods of Ursolic Acid: A Review.

Ursolic acid (UA) is a naturally occurring triterpenoid which is a promising candidate for the development of new therapeutic approaches and for the prevention and treatment of several diseases owing to its pharmacological importance. However, its low solubility in aqueous medium affects its therapeutic application. Several strategies have been used to overcome this obstacle. In this study, the incorporation of UA in to different drug delivery systems was found to be highly efficient. In addition, important investigations were performed about methods for qualitative and quantitative analyses of UA in various raw materials, including plants, biological fluids, and drug delivery systems, were investigated. Most recently high performance liquid chromatography coupled with various detectors, gas chromatography-mass spectrometry and capillary electrophoresis were used for this purpose. Thus, this review was performed to evaluate the biological effects of UA demonstrated thus far as well as the currently used, delivery systems and analytical methods.

Synthesis and factorial design applied to a novel chitosan/sodium polyphosphate nanoparticles via ionotropic gelation as an RGD delivery system.

Chitosan nanoparticles have been extensively studied for both drug and protein/peptide delivery. The aim of this study was to develop an optimized chitosan nanoparticle, by ionotropic gelation method, using 32 full factorial design with a novel polyanion, sodium polyphosphate, well known under the trade name Graham salt. The effects of these parameters on the particle size, zeta potential, and morphology and association efficiency were investigated. The optimized nanoparticles showed an estimated size of 166.20±1.95nm, a zeta potential of 38.7±1.2mV and an efficacy of association of 97.0±2.4%. The Atomic Force Microscopy (AFM) and Scanning Electronic Microscopy (SEM) revealed spherical nanoparticles with uniform size. Molecular interactions among the components of the nanoparticles and peptide were evaluated by Fourier Transform Infrared Spectra (FTIR) and Differential Scanning Calorimetry (DSC). The obtained results indicated that, the developed nanoparticles demonstrated high biocompatible, revealing no or low toxicity in the human cancer cell line (Caco-2). In conclusion, this work provides parameters that contribute to production of chitosan nanoparticles and sodium polyphosphate with desirable size, biocompatible and enabling successful use for protein/peptides delivery.