Drug carriers tailored to fit the physicochemical properties of anticancer agents and the therapeutic peculiarities of tumor management are envisioned for improving the effectiveness/toxicity ratio ...of the current treatments. Polymeric micelles are attracting much attention owing to their unique beneficial features: i) core-shell structure capable to host hydrophobic drugs, raising the apparent solubility in aqueous medium; ii) size adequate for a preferential accumulation (passive targeting) within the tumor, exhibiting enhanced permeability and retention (EPR effect), and iii) unimers that modulate the activity of efflux pumps involved in multidrug resistance (MDR). This review focuses on amphiphilic poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block copolymers, namely the linear poloxamers (Pluronic® or Lutrol®) and the X-shaped poloxamines (Tetronic®), as components of polymeric micelles able to play these three roles. Specific facets of poloxamers have been highlighted some years ago, but recently their wide range of possibilities is beginning to be fully elucidated and understood. Poloxamines are new excipients in the cancer arena and the comparison of their performance with that of poloxamers may enable to identify aspects of their architecture relevant for the optimization of micellar carriers. Clinical trials in progress indicate that drug-loaded polymeric micelles are beneficial regarding efficiency, safety, and compliance of the treatment and quality of life of the patients. The fact that some copolymers are already approved for internal use and several chemotherapy agents will be off patent soon may help to bring the clinical use of poloxamer- or poloxamine-based micelles into a reality in the coming years.
Determine the suitability of transcutaneous bilirubin (TCB) as a tool to assess the effectiveness of phototherapy on patched skin.
A prospective observational study was conducted. We covered a ...fragment of skin (sternum) with a photo-opaque patch. Several simultaneous TCB and TSB measurements were performed with the JM-105 bilirubinometer. Bland and Altman test evaluated the agreement between bilirubin levels.
A total of 217 patients were studied, 48.8% were preterm. The mean difference between TSB and TCB before the start of treatment was 1.07 mg/dL. During phototherapy, differences on covered skin were 0.52, 0.27, and 0.39 mg/dL at 24, 48, and 72 h of therapy respectively. The best correlation was observed at 48 h in preterm infants.
The measurement of TCB on patched skin (PTCB) is useful for monitoring the response to phototherapy in term and preterm infants. We use a patch with a removable flap that eases successive measures without disturbing the patients.
A supercritical carbon dioxide (scCO2)-assisted foaming/mixing method (SFM) was implemented for preparing dexamethasone (DXMT)-loaded poly(ɛ-caprolactone)/silica nanoparticles (PCL/SNPs) composite ...materials suitable for bone regeneration. The composites were prepared from PCL and mesoporous SNPs (MCM-41/SBA-15) by means of scCO2-assisted SFM at several operational pressures, processing times and depressurization conditions. DXMT was loaded into SNPs (applying a scCO2 solvent impregnation/deposition method – SSID) and into PCL/SNPs composites (using the SFM method). The effects of the employed operational and compositional variables on the physicochemical and morphological features as well as in the in vitro release profiles of DXMT were analyzed in detail. This work demonstrates that the above-referred scCO2-based methods can be very useful for the preparation of DXMT-loaded PCL/SNPs composites with tunable physicochemical, thermomechanical, morphological and drug release properties and suitable for hard-tissue regeneration applications.
Heroini constitute the second largest tribe of Neotropical cichlids and show their greatest diversity in Mesoamerica. Although heroine species are morphologically and ecologically very diverse, they ...were all historically assigned to one single genus,
Cichlasoma that was never formally revised from a phylogenetic point of view. Here, we present the most comprehensive molecular phylogeny of the tribe Heroini to date, based on the complete DNA sequence of the mitochondrial gene
cytochrome b, and the analysis of 204 individuals representing 91 species. Phylogenetic analyses did not support the monophyly of heroines because the genus
Pterophyllum was placed as the sister group of all remaining heroines plus cichlasomatines. However, the recovered relative position of
Pterophyllum was without strong statistical support. Within the remaining heroines,
Hyspelecara and
Hoplarchus are recovered with low support in a basal position with respect to a clade that includes
Heros,
Uaru,
Mesonauta, and
Symphysodon, and the circumamazonian (CAM) heroines. The first clade is restricted to South America. The largest clade of heroines, the CAM heroines, include more than 85% of the species within the tribe. This clade is mostly Mesoamerican, but also contains four species found in the Greater Antilles (
Nandopsis), and three genera found in South America (the
‘Heros’ festae group,
Australoheros, and
Caquetaia). Up to eight major lineages can be recovered within the CAM heroines, but the phylogenetic relationships among them remain unresolved. Two large suprageneric groups can be distinguished, the amphilophines and the herichthyines. The amphilophines include
Amphilophus,
Archocentrus,
Hypsophrys,
Neetroplus,
Parachromis,
Petenia, and five additional unnamed genera (the
‘Heros’ istlanus group, the
‘Amphilophus’ calobrensis group, the
‘Heros’ urophthalmus group, the
‘Heros’ wesseli group, and the
‘Heros’ sieboldii group). The herichthyines include the crown-group herichthyines (
Herichthys,
Theraps,
Vieja, and
Paratheraps) and the genera
Tomocichla,
Herotilapia, and
Thorichthys, together with three unnamed genera (the
‘Heros’ umbriferus group, the
‘Heros’ grammodes group, and the
‘Heros’ salvini group). Amphilophines are prevalent in southern Mesomerica south of the Motagua fault. Herichthyines have basal linages in Central America, whereas crown-group herichthyines and three related genera are found north from the Motagua fault. At least two independent origins are required to explain current Mesoamerican heroine distribution. Dispersal of heroines from South America into Mesoamerica was dated between 24 and 16 million years ago (MYA) based on geological calibrations and on standard fish mitochondrial cytochrome
b rates, respectively. These datings cannot be reconciled with currently known geological evidence, and the existence of a connection between Central America and South America in the Miocene needs to be postulated in order to explain the origins of Mesoamerican heroine lineages. However, our datings agree with those estimated for the dispersal of other secondary freshwater fishes (Rivulidae,
Synbranchus) into Mesoamerica, and predate the invasion of primary freshwater fishes by at least 10
myr.
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•Simvastatin was efficiently encapsulated in PLGA-based microparticles by spray-drying.•PLGA microparticles released osteogenic simvastatin hydroxyacid (SVA).•SVA concentration and ...microparticle formulation affected MSC proliferation and differentiation.•PLGA microparticles were embedded in fibroin/alginate beads alleviating SVA burst.•Microparticle-embedded fibroin/alginate beads promoted MSC differentiation into osteoblasts.
In the present work, we propose silk fibroin/alginate (SF/Alg) beads embedding simvastatin-loaded biodegradable microparticles as a versatile platform capable of tuning SVA release and in so doing osteogenic effects. In a first part of the study, microparticles of poly(lactic-co-glycolic) acid incorporating simvastatin either as lactone (SVL) or as hydroxyacid form (SVA) were prepared by spray-drying. While SVA-loaded microparticles released the drug in three days, long-term release of SVA could be obtained from SVL-loaded microparticles. In this latter case, SVL was promptly transformed to the osteogenic active SVA during release. When tested on mesenchymal stem cells, a time- and dose-dependent effect of SVL-loaded microparticles on cell proliferation and alkaline phosphatase (ALP) activity was found. Thereafter, SVL-loaded microparticles were embedded in SF/Alg beads to limit the initial simvastatin burst and to achieve easier implantation as well. Microparticle-embedded beads showed no cytotoxicity while ALP activity increased. If correctly exploited, the developed system may be suitable as osteogenic polymer scaffolds releasing correct amount of the drug locally for long time-frames.
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Superamphiphobic surfaces were evaluated as a tool to prepare spherical particles from polymers and solvents of very diverse nature, under mild conditions and with 100% drug ...encapsulation yield. Different from bioinspired superhydrophobic surfaces suitable only for aqueous dispersions, the superamphiphobic platforms allowed the formation of spherical droplets when solvents of any polarity were deposited onto them. Spherical poly(d,l-lactide-co-glycolide) (PLGA) particles were synthesized by placing drops of PLGA/ciprofloxacin suspensions in dioxane on a superamphiphobic surface followed by solvent evaporation. The particles prepared covering a wide range of PLGA/ciprofloxacin weight ratios delivered a 20% dose in the first 24h and then sustained the release of the remaining drug for more than 1month. The particles, both freshly prepared and after being 26days in the release medium, showed efficiency against different types of microorganisms. The developed polymer- and solvent-independent approach could be useful for microencapsulation with very high efficiency of active substances of varied nature into size-tunable particles for a wide range of applications in an affordable and cost-effective manner.
The goal of this work was to synthesize hybrid thin films prepared combining polyamide-6 (N6) and microcellulose (CE) at various weight ratios. Products exhibited improved mechanical properties, ...temperature-tunable hydrophilicity, and antimicrobial features. The obtained N6@CE films were grafted with
N
-vinylcaprolactam (NVCL) using gamma-rays, providing temperature responsiveness in a range of 37–38 °C. The grafting degree was studied as a function of CE percentage on the film, monomer concentration, and absorbed dose. The grafting degree increased with the percentage of CE on the film, and the maximum grafting was achieved at monomer concentration and the irradiation dose of 20% NVCL and 20 kGy, respectively. NVCL grafting was confirmed by SEM,
13
C-CPMAS NMR, FTIR-ATR, and XPS. SEM images attested formation of nanopores on the structure, caused by the grafting process, that consequently triggering on the new characteristics of the final materials. Potential performance of the composites as wound dressings was investigated in terms of their capability to loading and release of antimicrobial agents, such as vancomycin and benzalkonium chloride. NVCL grafting enhanced the uptake of both drugs, especially benzalkonium chloride, and regulated their release demonstrating antimicrobial effectiveness against
Staphylococcus aureus
.
Graphic abstract
Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly( N -isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical ...polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug.
Mixtures of 6.5-13% Pluronic F127 with α-cyclodextrin at concentrations above 5% result in supramolecular viscoelastic and thixotropic injectable gels that are able to control antimicrobial drug ...release.
The ability of Pluronic® F127 to form supramolecular gels in the presence of αCD has been explored as a way to design syringeable gel formulations able to sustain drug release while using the lowest proportion of both components. The effects of αCD concentration range (0–9.7%
w/v) in copolymer (6.5%, 13% and 20%) gel features were evaluated at 4, 20 and 37
°C. An effective complexation of Pluronic and αCD was evidenced as a change in the surface pressure of the π-A isotherm of Pluronic on a subphase of CD solution and the apparition of new peaks in the X-ray spectra. Once the Pluronic and αCD solutions were mixed, the systems became progressively turbid solutions or white gels. The greater the αCD concentration was, the faster the gel formation. The supramolecular hydrogels were thixotropic and those containing 5% or more αCD had G′ values above G″ at room temperature, but they were still easily syringeable. The values of both moduli increased as temperature raised; the effect being more evident for 13% and 20%
w/v copolymer. The gels prepared with low proportions of αCD exhibited phase separation in few days, particularly when stored at 4 or 37
°C. By contrast, those prepared with 6.5% copolymer were stable for at least two months when stored at 20
°C. The gels were able to sustain vancomycin release for several days; the higher the αCD proportion, the slower the release was. Furthermore, the drug-loaded gels showed activity against
Staphylococcus aureus. The results obtained highlight the role of the αCD concentration on the tuning of the rheological features and drug release profiles from Pluronic gels.
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