Rutin-loaded zein gel as a green biocompatible formulation for wound healing application.

Wound healing is a challenging clinical problem and efficient wound management is essential to prevent infection. This is best done by utilizing biocompatible materials in order to complete the healing in a rapid manner, with functional and esthetic outcomes. In this context, the zein protein fulfills the criteria of the ideal wound dressing which include non-toxicity and non-inflammatory stimulation. Zein gels containing rutin were prepared without any chemical refinement or addition of gelling agents in order to obtain a natural formulation characterized by antioxidant and anti-inflammatory properties to be proposed for the treatment of burns and sores. In vitro scratch assay showed that the proposed gel formulations promoted cell migration and a rapid gap closure within 24 h (~90 %). In addition, the in vivo activities of rutin-loaded zein gel showed a greater therapeutic efficacy in Wistar rats, with a decrease of the wound area of about 90 % at day 10 with respect to the free form of the bioactive and to DuoDERM®. The evaluation of various markers (TNF-α, IL-1ß, IL-6, IL-10) confirmed the anti-inflammatory effect of the proposed formulation. The results illustrate the feasibility of exploiting the peculiar features of rutin-loaded zein gels for wound-healing purposes.

Impact of airborne iron oxide nanoparticles on Tillandsia usneoides as a model plant to assess pollution in heavy traffic areas.

Due to the increasing evidence of widespread sub-micron pollutants in the atmosphere, the impact of airborne nanoparticles is a subject of great relevance. In particular, the smallest particles are considered the most active and dangerous, having a higher surface/volume ratio. Here we tested the effect of iron oxide (Fe3O4) nanoparticles (IONPs) with different mean diameter and size distribution on the model plant Tillandsia usneoides. Strands were placed in home-built closed boxes and exposed to levels of airborne IONPs reported for the roadside air, i.e. in the order of 107 - 108 items m-2. Plant growth and other morpho-physiological parameters were monitored for two weeks, showing that exposure to IONPs significantly reduced the length increment of the treated strands with respect to controls. A dose-dependence of this impairing effect was found only for particles with mean size of a few tens of nanometers. These were also proved to be the most toxic at the highest concentration tested. The IONP-induced hamper in growth was correlated with altered concentration of macro- and micronutrients in the plant, while no significant variation in photosynthetic activity was detected in treated samples. Microscopy investigation showed that IONPs could adhere to the plant surface and were preferentially located on the trichome wings. Our results report, for the first time, evidence of the negative effects of airborne IONP pollution on plant health, thus raising concerns about related environmental risks. Future research should be devoted to other plant species and pollutants to assess the impact of airborne pollution on plants and devise suitable attenuation practices.

Strategies of stabilization of zein nanoparticles containing doxorubicin hydrochloride.

Hybrid nanoparticles made up of zein and various stabilizers were developed and characterized. In detail, a zein concentration of 2 mg/ml was blended with various amounts of different phospholipids or PEG-derivatives in order to obtain formulations with suitable physico-chemical properties for drug delivery purposes. Doxorubicin hydrochloride (DOX) was used as a model of a hydrophilic compound and its entrapment efficiency, release profile and cytotoxic activity were investigated. Photon correlation spectroscopy showed that the best formulations were obtained using DMPG, DOTAP and DSPE-mPEG2000 as stabilizers of zein nanoparticles, which were characterized by an average diameter of ~100 nm, a narrow size distribution and a significant time- and temperature-dependent stability. The interaction between protein and stabilizers was confirmed through FT-IR analysis, while TEM analysis showed the presence of a shell-like structure around the zein core. The release profiles of the drug from the zein/DSPE-mPEG2000 nanosystems, evaluated at two pHs (5.5 and 7.4), showed a prolonged and constant leakage of the drug. The encapsulation of DOX within zein/DSPE-mPEG2000 nanosystems did not compromise its biological efficacy, demonstrating the potential application of these hybrid nanoparticles as drug carriers.

Unraveling the Role of Nickel Nanoparticles Functionalization in the Electronic Properties and Structural Features of 2D Black Phosphorene Exposed to Ambient Conditions.

Layered black phosphorus (BP) is endowed with peculiar chemico-physical properties that make it a highly promising candidate in the field of electronics. Nevertheless, as other 2D materials with atomic scale thickness, it suffers from easy degradation under ambient conditions. Herein, it is shown that the functionalization of BP with preformed and in situ grown Ni NPs, affects the electronic properties of the material. In particular, Ni functionalization performed in situ leads to a narrowing of the average BP band gap from 1.15 to 0.95 eV and to a marked shift in the conduction band maximum from -0.33 V to -0.07 V, which, in turn, improve the ambient stability. Structural studies carried out by XAS can well distinguish the two nanohybrids and reveal that once Ni NPs are grown on BP nanosheets, a Ni-P coordinative bond is formed, featuring a short Ni-P distance of 2.27 Å, which is not observed when preformed Ni NPs are immobilized on BP. Comparing the XANES and EXAFS spectra of fresh and aged samples of both nanohybrids, suggests that the interaction between Ni and P atoms results in a stabilization effect exerted via a dual electronic and redox mechanism, that infers a much superior ambient stability to BP, even if the surface functionalization is far to achieve a full coverage.

Gliadin Nanoparticles Containing Doxorubicin Hydrochloride: Characterization and Cytotoxicity.

Doxorubicin hydrochloride (DOX) is a well-known antitumor drug used as first line treatment for many types of malignancies. Despite its clinical relevance, the administration of the compound is negatively affected by dose-dependent off-target toxicity phenomena. Nanotechnology has helped to overcome these important limitations by improving the therapeutic index of the bioactive and promoting the translation of novel nanomedicines into clinical practice. Herein, nanoparticles made up of wheat gliadin and stabilized by polyoxyethylene (2) oleyl ether were investigated for the first time as carriers of DOX. The encapsulation of the compound did not significantly affect the physico-chemical features of the gliadin nanoparticles (GNPs), which evidenced a mean diameter of ~180 nm, a polydispersity index < 0.2 and a negative surface charge. The nanosystems demonstrated great stability regarding temperature (25−50 °C) and were able to retain high amounts of drug, allowing its prolonged and sustained release for up to a week. In vitro viability assay performed against breast cancer cells demonstrated that the nanoencapsulation of DOX modulated the cytotoxicity of the bioactive as a function of the incubation time with respect to the free form of the drug. The results demonstrate the potential use of GNPs as carriers of hydrophilic antitumor compounds.

Fluorescent Labeling of Lignin Nanocapsules with Fluorol Yellow 088.

The microscopic visualization of nanoparticles in plants is crucial to elucidate the mechanisms of their uptake through the cell wall and plasma membrane and to localize the possible sites of their extracellular or intracellular accumulation. Lignin nanocarriers are polymeric hollow nanocapsules able to contain and transport several bioactive substances inside plant tissues. We describe here a method for the preparation of Fluorol Yellow 088-labeled lignin nanocapsules that allow their localization in plant organs and tissues by fluorescence microscopy.

Microemulsions Enhance the In Vitro Antioxidant Activity of Oleanolic Acid in RAW 264.7 Cells.

Oleanolic acid (OA) is the main triterpenic acid of olive leaves known for numerous pharmacological properties, including antioxidant activity. However, it is poorly soluble in water and consequently with low bioavailability, which limits its pharmacological application. Microemulsions (MEs) are dispersed systems consisting of two immiscible phases that promote rapid solubilization and absorption in the gastrointestinal tract. To improve both solubility and intestinal permeability of this molecule, OA has been formulated in two different microemulsions (ME-1 and ME-2). A solubility screening was carried out to select the ME components, and pseudoternary phase diagrams were constructed to evaluate the region of existence and select the appropriate amount of the constituents. ME-1 was prepared using Capmul PG-8/NF as the oily phase, and Transcutol and Tween 20 (7:3) as surfactants, while ME-2 contained Nigella oil and Isopropil myristate as the oily phase, and Transcutol HP and Cremophor EL (2:1) as surfactants. The OA solubility was increased by 1000-fold and 3000-fold in ME-1-OA and ME-2-OA, respectively. The MEs' droplet size and the PdI were evaluated, and the stability was assessed for 8 weeks by monitoring chemical and physical parameters. The parallel artificial membrane permeability assay (PAMPA) also demonstrated an enhanced intestinal permeability of both OA formulations compared with free OA. The potential ability of both MEs to enhance the bioactivity of OA against LPS-induced oxidative stress in RAW 264.7 murine macrophages was also investigated. Overall, this study suggests that both MEs promote a bio-enhancement of the protective action of OA against the LPS-induced pro-oxidant stress in macrophages. Overall, this study suggests that MEs could be an interesting formulation to improve OA oral bioavailability with potential clinical applications.

Solubility and Permeability Enhancement of Oleanolic Acid by Solid Dispersion in Poloxamers and γ-CD.

Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in the Oleaceae family, and it represents 3.5% of the dry weight of olive leaves. OA has many pharmacological activities, such as hepatoprotection, anti-inflammatory, anti-oxidant, anti-diabetic, anti-tumor, and anti-microbic activities. Its therapeutic application is limited by its poor water solubility, bioavailability, and permeability. In this study, solid dispersions (SDs) were developed to overcome these OA limitations. Solubility studies were conducted to evaluate different hydrophilic polymers, drug-to-polymer ratios, and preparation methods. Poloxamer 188, Poloxamer 407, and γ-CD exhibited the highest increases in terms of OA solubility, regardless of the method of preparation. Binary systems were characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). In addition, pure compounds and SDs were analyzed using scanning electron microscopy (SEM) in order to observe both the morphology and the particle surface. In vitro dissolution studies were performed for P407, P188, and γ-CD SDs. Preparation using the solvent evaporation method (SEM) produced the highest increase in the dissolution profiles of all three polymers with respect to the OA solution. Finally, the effect of SDs on OA permeability was evaluated with an in vitro parallel artificial membrane permeability assay (PAMPA). The formulation improved passive permeation across the simulated barrier due to OA increased solubility. The dissolution and PAMPA results indicate that the amorphization of OA by SD preparation could be a useful method to enhance its oral absorption, and it is also applicable on an industrial scale.

Influence of the Dispersion Medium and Cryoprotectants on the Physico-Chemical Features of Gliadin- and Zein-Based Nanoparticles.

The evaluation of the physico-chemical features of nanocarriers is fundamental because the modulation of these parameters can influence their biological and in vivo fate. This work investigated the feasibility of saline, 5% w/v glucose and phosphate-buffered saline solution, as polar media for the development of nanoparticles made up of two vegetal proteins, zein from corn and gliadin from wheat, respectively. The physico-chemical features of the various systems were evaluated using dynamic and multiple light scattering techniques, and the results demonstrate that the 5% w/v glucose solution is a feasible medium to be used for their development. Moreover, the best formulations were characterized by the aforementioned techniques following the freeze-drying procedure. The aggregation of the zein nanoparticles prepared in water or glucose solution was prevented by using various cryoprotectants. Mannose confirmed its crucial role in the cryopreservation of the gliadin nanosystems prepared in both water and glucose solution. Sucrose and glucose emerged as additional useful excipients when they were added to gliadin nanoparticles prepared in a 5% glucose solution. Specifically, their protective effect was in the following order: mannose > sucrose > glucose. The results obtained when using specific aqueous media and cryoprotectants permitted us to develop stable zein or gliadin nanoparticles as suspension or freeze-dried formulations.

Evaluation of the increase of the thymoquinone permeability formulated in polymeric micelles: In vitro test and in vivo toxicity assessment in Zebrafish embryos.

Thymoquinone (TQ) is a natural compound present in the essential oil and in the fixed oil of Nigella sativa L. Like many natural substances, it is characterized by poor aqueous solubility and low stability which limit its bioavailability. Soluplus®-Solutol® HS15 polymeric micelles (TQ-MP) were developed to increase the permeability of TQ with particular attention to overcoming intestinal barrier and the blood brain barrier, for possible oral and parenteral administration. The optimized micelles have dimensions < 100 nm and PdI < 0.2 indicating that the formulation was homogeneous as confirmed also by TEM experiments. EE% was 92.4 ± 0.3%. Stability studies showed a stable formulation following subsequent dilutions and in the gastric-intestinal media. In vitro studies have revealed that the carrier enhances the permeability of TQ in the intestine and in the blood-brain barrier using Parallel Artificial Membrane Permeability Assay (PAMPA) assay and cellular tests with Caco-2 cells and hCMEC/D3 monolayer cells. Up-take study, cell viability and cytotoxicity studies were also conducted. Fluorescent micelles (FITC-MP), were also optimized to perform in vitro up-take study in Caco-2 cells and to study their toxicity in Zebrafish model. The toxicity was evaluated on three lines of Zebrafish: wild type, transgenic line Tg(Myl7:EGFP) in which cardiomyocytes are marked with green fluorescence protein and Tg(flk1-GFP) line which expresses GFP under the control of the vascular endothelial growth factor receptor 2 (vegfr2) promoter.

Phospholipid/zein hybrid nanoparticles as promising carriers for the protection and delivery of all-trans retinoic acid.

A totally biodegradable mixed system made up of phospholipids and zein was developed in order to effectively improve the photostability of all-trans retinoic acid (ATRA) preserving its pharmacological properties. Photon correlation spectroscopy showed that the formulation obtained using phospholipon 85G and zein at a ratio of 7:3 w/w was characterized by an average diameter of less than 200 nm, a narrow size distribution and a significant time- and temperature-dependent stability. The use of specific cryoprotectants such as mannose and glucose favoured the long-term storage of the nanocarriers after the freeze-drying procedure. The nanoparticles increased the stability of the ATRA against photochemical degradation with respect to the free drug and its antitumor effect was preserved as a consequence of the cell uptake of the colloidal systems. The results demonstrate the potential of the proposed hybrid nanosystems to provide a high level of stabilization for sensitive and labile antitumor compounds.

Development of polyoxyethylene (2) oleyl ether-gliadin nanoparticles: Characterization and in vitro cytotoxicity.

Natural polymers have been widely investigated as materials for the delivery of active compounds as a consequence of their biocompatibility, low-cost and the opportunity they furnish to obtain micro- and nanostructures. In this investigation, commercial wheat gliadin was used as raw material with the aim of obtaining a vegetal protein-based nanoformulation to be used for various applications. The influence of non-ionic and anionic surfactants on the physico-chemical properties of gliadin nanoparticles was evaluated in order to propose a suitable candidate able to stabilize the colloidal structure. The use of Super Refined polyoxyethylene (2) oleyl ether gave the best results, promoting the formation of spherical-shaped nanosystems with a narrow size distribution. The oleyl ether-based emulsifier prevented the destabilization of the colloidal systems when pH- and temperature-dependent stress was applied. A freeze-dried formulation was obtained when mannose was used as a cryoprotectant. Polyoxyethylene (2) oleyl ether-stabilized nanosystems were shown to retain and release both hydrophilic and lipophilic model compounds in a controlled manner. The cytotoxicity of the surfactant-free and polyoxyethylene (2) oleyl ether-stabilized gliadin based nanosystems was assessed on human cells, both normal and tumoural, in order to investigate the concentrations of particles that can be used during in vitro experiments. Polyoxyethylene (2) oleyl ether-stabilized gliadin-based nanosystems are promising carriers for the delivery of several active compounds.

Brij-stabilized zein nanoparticles as potential drug carriers.

The current study was designed to provide a preliminary physico-chemical characterization of zein nanosystems prepared with various Brij surfactants (for the first time to the best of our knowledge) as a function of various external stimuli such as temperature, pH, serum incubation and the freeze-drying process. The results demonstrate that when Brijs are characterized by unsaturation (C18), considerable stabilization of the colloidal structure is promoted while the length of the polyethylene glycol fraction does not significantly modulate the physico-chemical properties of the nanosystems. Specifically, dynamic light scattering and nanoparticle tracking analysis demonstrated that the use of 0.2 % w/v of Brij O10 promoted the formation of stable zein nanosystems with mean sizes of ∼150 nm and a narrow size distribution, preserving their structures at various pHs and temperatures. The use of mannitol as cryoprotectant resulted in a formulation that can easily be re-suspended in water after the freeze-drying process. This nanoformulation demonstrated that it efficiently retained different amounts of both hydrophilic and lipophilic compounds and showed a prolonged release of the entrapped molecules. In addition, the nanosystems showed a favorable degree of in vitro safety on various cell lines when a concentration <50 µg/mL of protein was used, demonstrating the potential application of Brij O10-stabilized zein nanoparticles as innovative nanocarriers of several active compounds.

Green and cost-effective synthesis of copper nanoparticles by extracts of non-edible and waste plant materials from Vaccinium species: Characterization and antimicrobial activity.

The aim of this work was the green synthesis of copper nanoparticles (Cu-NPs) using aqueous extracts of (i) bilberry (Vaccinium myrtillus L.) waste residues from the production of fruit juices and (ii) non-edible "false bilberry" fruits (Vaccinium uliginosum L. subsp. gaultherioides). Different cupric salts (CuCl2, Cu(CH3COO)2 and Cu(NO3)2) were used for the synthesis. The formation of stable nanoparticles (CuNPs) was assessed by transmission electron microscopy and the oxidation state of copper in these aggregates was followed by X-ray photoelectron spectroscopy. The polyphenol composition of the extracts was characterized, before and after the synthesis, using spectrophotometric methods (i.e. total soluble polyphenols and total monomeric anthocyanins) and high-performance liquid chromatography coupled with tandem mass spectrometry (i.e. individual anthocyanins). Polyphenol concentration in the extracts was found to decrease after the synthesis, indicating their active participation to the processes, which led to the formation of Cu-NPs. The antimicrobial activity of Cu-NPs, berry extracts, and cupric ion solutions were analysed by broth microdilution and time-kill assays, on prokaryotic and eukaryotic models. The antimicrobial activity of Cu-NPs, especially those derived from bilberry waste residues, appeared to be higher for both Gram-negative and Gram-positive bacteria, and for fungi, compared to the ones of its single components (cupric salts and berry extracts). Therefore, Cu-NPs from the green synthesis here proposed can be considered as a cost-effective sanitization tool with a wide spectrum of action.

Effect of manual, preloaded, and automated preloaded injectors on corneal incision architecture after IOL implantation.

PURPOSE: To analyze the effects on corneal morphology of manual, preloaded, and automated preloaded intraocular lens (IOL) injectors in eye bank human corneas by environmental scanning electron microscopy (ESEM) and in patients after phacoemulsification using anterior segment optical coherence tomography (AS-OCT). SETTINGS: Eye Clinic, Careggi University Hospital, Florence, Italy. DESIGN: Retrospective and experimental study. METHODS: Seventy-eight corneal incisions were examined after IOL implantation: 30 in human corneas mounted on an artificial chamber using ESEM (ex vivo); 48 in patients undergoing phacoemulsification (in vivo). Three different injectors were used for both analyses: manual (Monarch III, n = 26), manual preloaded (UltraSert, n = 26), and automated preloaded system (AutonoMe, n = 26). Thirty IOLs were implanted in the ex vivo study: 5 intermediate and 5 high dioptric powers for AcrySof IQ (Monarch and UltraSert) and for Clareon (AutonoMe) IOLs. In the in vivo analysis, 16 corneal wounds for each injector were evaluated using AS-OCT; in the ex vivo study, incision width was measured and Descemet membrane detachment, posterior wound retraction, and posterior gape were analyzed. RESULTS: In the eye bank corneas, the incision width was significantly wider in the high dioptric power IOL manual subgroup (P < .05), with more Descemet tearing compared with AutonoMe. In the in vivo study, the incidence of Descemet membrane detachment, posterior gape, and wound retraction was lower in the automated preloaded group at 1 postoperative day 1. CONCLUSIONS: The automated preloaded injector ensured less trauma to the wound and contributed to preserving the endothelial side of the incision even during the implantation of high-power IOLs and in the early postoperative period.

Comparison of Chitosan Nanoparticles and Soluplus Micelles to Optimize the Bioactivity of Posidonia oceanica Extract on Human Neuroblastoma Cell Migration.

Posidonia oceanica (L.) Delile is a marine plant endemic of Mediterranean Sea endowed with interesting bioactivities. The hydroalcholic extract of P. oceanica leaves (POE), rich in polyphenols and carbohydrates, has been shown to inhibit human cancer cell migration. Neuroblastoma is a common childhood extracranial solid tumor with high rate of invasiveness. Novel therapeutics loaded into nanocarriers may be used to target the migratory and metastatic ability of neuroblastoma. Our goal was to improve both the aqueous solubility of POE and its inhibitory effect on cancer cell migration. METHODS: Chitosan nanoparticles (NP) and Soluplus polymeric micelles (PM) loaded with POE have been developed. Nanoformulations were chemically and physically defined and characterized. In vitro release studies were also performed. Finally, the inhibitory effect of both nanoformulations was tested on SH-SY5Y cell migration by wound healing assay and compared to that of unformulated POE. RESULTS: Both nanoformulations showed excellent physical and chemical stability during storage, and enhanced the solubility of POE. PM-POE improved the inhibitory effect of POE on cell migration probably due to the high encapsulation efficiency and the prolonged release of the extract. CONCLUSIONS: For the first time, a phytocomplex of marine origin, i.e., P. oceanica extract, has enhanced in terms of acqueous solubility and bioactivity once encapsulated inside nanomicelles.

Development and Percutaneous Permeation Study of Escinosomes, Escin-Based Nanovesicles Loaded with Berberine Chloride.

Escin is a natural saponin, clinically used for the anti-edematous and anti-inflammatory effects. The aim of the study was to explore the possibility of converting escin into vesicle bilayer-forming component. The hyaluronidase inhibition activity of escin was evaluated after its formulation in escinosomes. Berberine chloride, a natural quaternary isoquinoline alkaloid isolated from several medicinal plants that is traditionally used for various skin conditions was loaded in the vesicles. The developed nanovesicles were characterized in terms of diameter, polydispersity, ζ-potential, deformability, recovery, encapsulation efficiency, stability, and release kinetics. Nanovesicle permeation properties through artificial membranes and rabbit ear skin were investigated using skin-PAMPATM and Franz cells were also evaluated. Escinosomes, made of phosphatidylcholine and escin, were loaded with berberine chloride. These nanovesicles displayed the best characteristics for skin application, particularly optimal polydispersity (0.17) and deformability, high negative ζ-potential value, great encapsulation efficiency (about 67%), high stability, and the best release properties of berberine chloride (about 75% after 24 h). In conclusion, escinosomes seem to be new vesicular carriers, capable to maintain escin properties such as hyaluronidase inhibition activity, and able to load other active molecules such as berberine chloride, in order to enhance or expand the activity of the loaded drug.

New insights into sperm with total globozoospermia: Increased fatty acid oxidation and centrin1 alteration.

Sperm morphology and lipid profile have a relevant role in male fertility. We explore the status of the sperm centriole, essential structure for human fertilization and the role of fatty acid oxidation in globozoospermia, a rare sperm pathology causing infertility. A case of globozoospermia was characterized by light and electron microscopy, sperm immunolocalization was performed for centrin1, 8-iso-PGF2α and peroxisome proliferator γ activated receptor gamma (PPARγ). In semen and sperm pellet, F2-isoprostanes (F2-IsoPs) levels were determined. Finally, the cytosolic phospholipase A2 (cPLA2) assessment was carried out in spermatozoa. The experiments were also performed in sperm from three fertile men. The results of electron microscopy analysis showed spermatozoa were round-headed without acrosome and with tail coiled around the nucleus characterized by immature chromatin. Centrin1 was located around the head in globozoospermic sperm, whereas, in sperm of controls, it appears as two spots. The 8-iso-PGF2α was detected around the head and in the cytoplasmic residue; PPARγ was mainly present in the cytoplasmic residue and under the head. The fluorescent signals for all molecules were different in the sperm of fertile men. F2-IsoPs levels, determined both in semen and sperm, were significantly increased (P < 0.05) and sperm cPLA2 was significantly decreased (P < 0.05) in the globozoospermic patients versus fertile subjects. In conclusion, sperm with globozoospermia showed an increased susceptibility to non-enzymatic fatty acid oxidation that could be, at least in part, responsible for fertilization failure in intracytoplasmic sperm injection. The opportunity to study a peculiar sperm pathology, as globozoospermia, could provide new insights in the relationship between lipid peroxidation and male infertility. Abbreviations: PPARγ: peroxisome proliferator γ activated receptor gamma; F2-IsoPs: F2-isoprostanes; cPLA2: cytosolic phospholipase A2; ICSI: Intracytoplasmic Sperm Injection; PLCζ: phospholipase C zeta; PUFAs: polyunsaturated fatty acid; AA: arachidonic acid; PLA2: phospholipase A2; SEM: scanning electron microscopy; TEM: transmission electron microscopy; AB: aniline blue; AO: acridine orange; FA: fatty acid; 8-iso-PGF2α: 8-iso-prostaglandin F2α; WHO: World Health Organization; DAPI: 4,6-Diamidino-2-phenylindole; PBS: phosphate buffered saline; GC/NICI-MS/MS: gas chromatography/negative-ion chemical ionization tandem mass spectrometry; BHT: butylated hydroxytoluene; PGF2α-d4: tetradeuterated derivative of Prostaglandin F2α; ELISA: enzyme-linked immunosorbent assay.

Sclareol-loaded hyaluronan-coated PLGA nanoparticles: Physico-chemical properties and in vitro anticancer features.

Sclareol (labd­14­ene­8,13­diol), a phytochemical compound belonging to labdane-type diterpenes, has recently attracted noteworthy attention because of its peculiar pharmacological properties. The foremost obstacle to an efficacious application and use of this molecule is its unfavorable bioavailability due to its poor aqueous solubility. In this investigation sclareol was encapsulated within PLGA nanoparticles with the aim of favoring its administration in physiological media, increasing its anticancer activity and obtaining a stable colloidal formulation. These nanoparticles containing sclareol were characterized by a mean diameter of 100-150 nm, a narrow size distribution and a negative surface charge. The active compound was efficiently retained by the polymeric structure and did not induce any physical destabilization. The coating of the PLGA nanoparticles with hyaluronic acid (1.5 MDa) increased the antitumor efficacy of the encapsulated drug against human breast cancer cells expressing the hyaluronan receptors (MCF-7 and MDA-MB468) while a similar pharmacological effect was obtained on human colon carcinoma cells (CaCo-2). CLSM analysis demonstrated the intracellular localization of fluorescent nanosystems after 3 h incubation.

Corneal incision architecture after IOL implantation with three different injectors: an environmental scanning electron microscopy study.

PURPOSE: To evaluate by Environmental Scanning Electron Microscopy (ESEM) the corneal incision architecture after intraocular lens (IOL) implantation in pig eyes, using manual, automated injectors or preloaded delivery systems. METHODS: Twenty-four pig eyes underwent IOL implantation in the anterior chamber using three different injectors: manual (Monarch III) (n = 8), automated (AutoSert) (n = 8), or a preloaded system (UltraSert) (n = 8). Acrysof IQ IOLs, 21 Dioptres (D) (n = 12) and 27D (n = 12), were implanted through 2.2 mm clear corneal incisions. Incision width was measured using corneal calipers. The endothelial side of the incision was analyzed with ESEM. RESULTS: In each group, the final size of the corneal wound after IOL implantation, measured by calipers, was 2.3-2.4 mm. The incision architecture resulted more irregular in the Monarch group compared with the other injectors. In every group the 27D IOL-implanted specimens showed more alterations than in 21D IOL-implanted samples, and this was less evident in the UltraSert group. The Descemet tear length was higher in the Monarch group than AutoSert and UltraSert group. CONCLUSIONS: The automated and preloaded delivery systems provided a good corneal incision architecture; after high-power IOL implantation the incisions were more regular and less damaged with the preloaded system than with the other devices.