1,721,430 research outputs found
Polyaspartamide based hydrogel with cell recruitment properties for the local administration of hydrophobic anticancer drugs
No full textBy exploiting the chemical versatility and the high water dispersibility of α,β-poly(N-2-hydroxyethyl)D,L-aspartamide, in this work, two different polymer derivatives were synthesized for the first time. Obtained macromolecules were characterized and used to produce hydrogels exploitable for the local release of hydrophobic anticancer drugs. The first derivative, bearing pendant β-cyclodextrins, was employed to solubilize tamoxifen, chosen as a model drug, and to produce a water soluble supramolecular complex, as evidenced through tamoxifen phase solubility studies. The second derivative, bearing pendant Cyclo(Arginine-Glyicine-Asparagine-D-Phenilyalanine-Cysteine) peptide moieties, was used as a macromolecular crosslinker to obtain a hydrogel with cellular recruitment properties. The occurrence of crosslinking between the two derivatives was studied through rheological analysis and different procedures were employed to obtain tamoxifen medicated hydrogels. In vitro release studies, together with cytotoxicity and recruitment experiments, reveal that the obtained hydrogels can control the release of anticancer drugs, have a cytotoxic effect on human breast carcinoma cells and, thanks to the presence of adhesion moieties, are able to recruit cancer cells
Graphene nanosystems as supports in siRNA Delivery
No full textThe nature of graphene-based nanosystems, as well as the possibility to synthesize them at low cost, have made them in the last few years, an interesting proposition in tumour therapy as a drug delivery system. Here, a reduced form of graphene oxide (RGO) has been synthesized and conjugated with a specific antibody for active targeting against tumour cells (RGOY). Furthermore, its bi-dimensional nature permits also p- p stacking interactions with planar molecules like siRNA (RGOY-siRNA). All these nano-complexes were characterized by DLS and DSC analysis, TEM and Raman spectroscopy and their biocompatibility was demonstrated by viability assay on cell line ECV 304. The system is able to be internalized from cells, as demonstrated by uptake studies with confocal microscopy, performed using its red fluorescence variant (RGOY-AF). A high reduction of the stacking interactions between the graphene sheets was obtained by conjugating RGOY particles to polyvinylpyrrolidone (PVP) (RGOY-PVP). The addition of PVP did not alter the biocompatibility of the system, but limited the formation of aggregates due to the stacking interaction between the graphene sheets: the complexes appeared more dispersed and able to enter into the cells after only few minutes, and in higher amounts with respect to the complex without PVP. All obtained data indicate graphene nanosystems very good candidates as delivery system thanks to their specific properties that permit to link to both antibody and siRNA without any degradation effect
Photocycle of Excitons in Nitrogen-Rich Carbon Nanodots: Implications for Photocatalysis and Photovoltaics
Full text linkNitrogen-rich carbon nanodots have emerged as promising nanomaterials for a wide range of applications where a highly emissive and photoactive material with low toxicity and cost-effectiveness is required. One of their hallmarks is indeed a bright, tunable fluorescence of excitonic nature. Disentangling the origin of their optical absorption and fluorescence properties and uncovering relaxation channels and interactions with solvents are some of the most debated issues in the field. Uncovering these aspects is essential for targeted applications, especially in the fields of photocatalysis but also photovoltaics and optoelectronics. Here, we present dedicated transient absorption measurements of purified monodispersed nanodots covering all relevant electronic transitions. Monodispersed nanodots of about 6 nm size exhibit well-separated absorption and emission features and allow us to unambiguously establish the complete and size-independent femtosecond-to-nanosecond photocycle of nitrogen-rich carbon nanodots. Further rigorous analysis shows that the often complex absorption and emission spectra of an ensemble of nanodots with a broad size distribution result from the superposition of individual size-selective contributions
A Fluorescent Molecular Sensor for pH Windows in Traditional and Polymeric Biocompatible Micelles: Comicellization of Anionic Species To Shift and Reshape the ON Window
No full textA new approach is presented to obtain fluorescent sensors for pH windows that work in water and under biomimetic conditions. A single molecule that features all-covalently linked components is used, thus making it capable of working as a fluorescent sensor with an OFF/ON/OFF response to pH value. The components are a tertiary amine, a pyridine, and a fluorophore (pyrene). The forms with both protonated bases or both neutral bases quench the pyrene fluorescence, whereas the form with the neutral pyridine and protonated amine groups is fluorescent. The molecular sensor is also equipped with a long alkyl chain to make it highly hydrophobic in all its protonated and unprotonated forms, that is, either when neutral or charged. Accordingly, it can be confined at any pH value either in traditional (i.e., low-molecular-weight) nonionic surfactant micelles or inside polymeric, biocompatible micellar containers. Relevant for future applications in vivo, thanks to its strong hydrophobicity, no leakage of the molecular sensor is observed from the polymeric biocompatible micelles. Due to the proximity of the pyridine and amine functions in the molecular structure and the poor hydration inside the micelles, the observed pK(a) values are low so that the ON window is positioned at very low pH values. However, the window can be shifted to biologically relevant values by comicellization of anionic species. In particular, in the micelles of the nonionic surfactant TritonX-100, a shift of the ON window to pH 4-6 is obtained by addition of the anionic sodium dodecyl sulphate surfactant, whose negative charge promotes the stability of the protonated forms of the pyridine and amine fragments. In the case of the polymeric micelles, we introduce the use of the amphiphilic polystyrene sulfonate anionic polyelectrolyte, the comicellization of which induces a shift and sharpening of the ON window that is centered at pH
Printable Thermo- and Photo-stable Poly(D,L-lactide)/Carbon Nanodots Nanocomposites via Heterophase Melt-Extrusion Transesterification
No full textWe propose for the first time an one-pot synthesis of carbon nanodots-poly(D,L-lactide) (CDs-PLA) nanocomposites, obtained by a simple reactive melt-extrusion process involving polar surface groups of multicolor CDs and ester bonds of PLA chains. Apart from providing an excellent method to produce polyester-coated CDs, our protocol allows obtaining perfect PLA@CDs blends giving rise to homogeneous extruded PLA@CDs filaments (ePLA@CDs) suitable for 3D printing applications (e.g., additive manufacturing for biomaterials and biodegradable encoded polymer ink technology). We demonstrate that ePLA@CDs filaments can be used to build a huge range of fluorescent objects with increasing architectural complexity (from grids to orthopedic screws). The designed nanocomposite synergistically combines the brilliant optical properties of hydrophilic N,S-CDs with the known biodegradable and biocompatible properties of PLA. Indeed, CDs endow PLA with peculiar thermo- and photo-stable multicolor emission (from blue to NIR) as well as good printability, avoiding typical self-quenching phenomena of CDs in solid-state. Besides, the use of CDs as probe-filler assumes a multifunctional role improving water uptake, degradation rate and also increasing material-cell interactions in comparison with the plain PLA. Overall, our results pave the way for the design of fluorescent implants providing real-time localization and monitoring of degradation state via non-invasive fluorescence imaging
Spray-Drying, Solvent-Casting and Freeze-Drying Techniques: a Comparative Study on their Suitability for the Enhancement of Drug Dissolution Rates
Full text linkPurpose Solid dispersions (SDs) represent the most common
formulation technique used to increase the dissolution rate of
a drug. In this work, the three most common methods used to
prepare SDs, namely spray-drying, solvent-casting and freezedrying,
have been compared in order to investigate their effect
on increasing drug dissolution rate.
Methods Three formulation strategies were used to prepare
a polymer mixture of polyvinyl-alcohol (PVA) and maltodextrin
(MDX) as SDs loaded with the following three model
drugs, all of which possess a poor solubility: Olanzapine,
Dexamethasone, and Triamcinolone acetonide. The SDs
obtained were analysed and compared in terms of drug particle
size, drug-loading capacity, surface homogeneity, and
dissolution profile enhancement. Physical-chemical characterisation
was conducted on pure drugs, as well as the formulations
made, by way of thermal analysis and infrared
spectroscopy.
Result The polymers used were able to increase drug saturation
solubility. The formulation strategies affected the drug
particle size, with the solvent-casting method resulting inmore
homogenous particle size and distribution when compared to
the other methods. The greatest enhancement in the drug
dissolution rate was seen for all the samples prepared using
the solvent-casting method.
Conclusion All of the methods used were able to increase the
dissolution rate of the pure drugs alone, however, the solventcasting
method produced SDs with a higher surface homogeneity,
drug incorporation capability, and faster dissolution
profile than the other techniques
Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs
No full textChitosan oligosaccharide (C) was functionalized with L-arginine (A) and short hydrocarbon chains (C8) to design an amphiphilic copolymer, henceforth CAC8, leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). L-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC8 MPs (CAC8-MPs) were studied, showing that CAC8-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC8-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity
Chemical stiffening of constructs between polymeric microparticles based on a hyaluronic acid derivative and mesenchymal stem cells: rheological and in vitro viability studies
No full textOur research group has recently developed microparticles of a hyaluronic acid derivative used for bottom-up growth of microparticles/human mesenchymal stem cells (hMSCs). In this work, we investigated a strategy to increase the stiffening of aggregated constructs between microparticles and hMSCs. In particular, we applied a Michael-type crosslinking procedure between microparticles to allow a chemically driven and cell-compatible stiffening of constructs. Two batches of microparticles were functionalized with thiol and maleimide groups, respectively, and were then mixed to allow chemical crosslinking. The adhesion of hMSCs was controlled through addition of the adhesive peptide cyclo(-Arg-Gly-Asp-D-Phe-Cys) (cyRGDC). Rheological measurements performed in this study showed that the chemical stiffening strategy allows the G′ modulus of bottom-up growing constructs to be increased, while viability tests suggest that the chemical procedure did not negatively affect cell viability compared with constructs obtained without chemical crosslinking. © 2018 Society of Chemical Industry
SPIONs Embedded in Polyamino acid Nanogels to Synergistically Treat Tumor Microenvironment and Breast Cancer Cells
No full textThe extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named "Theranomics", which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enhance tumor penetration of nanomedicines and the in situ sustained release of the drug payload throughout 3-D tumor spheroids up to the core (parenchyma), thus enabling a synergistic and efficient anticancer effect toward highly invasive breast tumors. We illustrate that SPIONs/Doxo@Col is also capable of reducing the invasivity of cancer cells
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