1,721,049 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
Thermosensitive and mucoadhesive Xanthan gum-based hydrogel for local release of anti-Candida peptide
No full textA thermoresponsive and mucoadhesive hydrogel has been developed for the local delivery of a novel anti-
Candida peptide. This antimicrobial peptide was custom-designed and synthesized, utilizing a natural peptide
identified in the hemolymph of the freshwater crayfish Procambarus clarkii as a molecular scaffold. The hydrogel,
fabricated from a xanthan gum/poly-N-isopropylacrylamide graft copolymer, demonstrates temperature-
dependent viscoelastic properties and a pseudoplastic behaviour, making it suitable for potential administra-
tion in various tissues. Moreover, the high stability of the hydrogel (about 9 % weight loss after 24 h of incu-
bation) in physiological fluids as well as its mucoadhesive properties indicate that it could withstand in the
application site long enough to perform its intended function. Furthermore, the good cytocompatibility of the
hydrogel and the peptide’s release profile (approximately 90 % release within the first 24 h), coupled with its
efficacy in inhibiting fungal growth (logarithmic reduction of 1.08 compared to the control), validates the
prospective application of the formulation in managing mucosal and superficial skin C. albicans infections. This
not only addresses concerns related to drug resistance but also establishes the hydrogel as a versatile platform for
advanced drug delivery systems aimed at circumventing systemic administration of antifungal drugs for the
treatment of superficial skin and mucosal candidiasis
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
Near-infrared light-responsive and antibacterial injectable hydrogels with antioxidant activity based on a Dopamine-functionalized Gellan Gum for wound healing
No full textThe development of wound dressings with combined antioxidant, antibacterial and tissue adhesion functions has been a difficult medical task for the treatment of wound infections. We synthetized a dopamine and PEG functionalized Gellan Gum (GG) to produce an injectable hydrogel with radical scavenging activity having both specific and aspecific antibiotic/antimicrobial properties. Using starting GG with different molecular weights, we obtained two derivatives that have been used to prepare the gel precursor dispersion, that undergoes gelation in the presence of colistin and dried microparticles (MPs) functionalized on the surface with polydopamine (pDA). Both were used to dope the hydrogel, increase the radical scavenger activity and impart near-infrared light (NIR) responsiveness. Indeed, with an irradiation of 810 nm, the incorporated microparticles exhibit photothermal transformation properties and improve the release of antibiotics on demand. The combination of photothermal and antibiotic therapy with synergistic antibacterial action acts on Pseudomonas aeruginosa and leads to a bactericidal effect in a few hours, while on Staphylococcus aureus there is an effect of inhibition of growth over time due only to the hyperthermic effect. We believe this study provides a promising method for fabricating a multifunctional injectable hydrogel for the potential treatment of infected skin wounds
Multifibrillar bundles of a self-assembling hyaluronic acid derivative obtained through a microfluidic technique for aortic smooth muscle cell orientation and differentiation
No full textA hyaluronic acid derivative that is able to physically crosslink in a saline aqueous environment was employed for the production of fibers with a mean diameter of 50 μm using a microfluidic technique. The microfibers were collected in a tailored rotating collector and assembled to form multifibrillar bundles. The orientation of the microfibers on the collected bundles was evaluated by microCT analysis. The bundles were biofunctionalized by physical addition of fibronectin or chemical tethering of a cyRGDC peptide to achieve control of Aortic Smooth Muscle Cell (AoSMC) attachment, elongation and alignment. The mechanical performances of these bundles were evaluated by elongation tests, related to the kind of biological functionalization and compared to non-functionalized samples. The alignment and differentiation of AoSMCs on single fibers and on the bundles were evaluated by microscopy and histochemical analyses
Inulin Derivatives Obtained Via Enhanced Microwave Synthesis for Nucleic Acid Based Drug Delivery
No full textA new class of therapeutic agents with a high potential for the treatment of different socially relevant human diseases is represented by Nucleic Acid Based Drugs (NABD), including small interfering RNAs (siRNA), decoy oligodeoxynucleotides (decoy ODN) and antisense oligonucleotides (ASOs). Although NABD can be engineered to be specifically directed against virtually any target, their susceptibility to nuclease degradation and the difficulty of delivery into target tissues severely limit their use in clinical practice and require the development of an appropriate nanostructured delivery system. For delivery of NABD, Inulin (Inu), a natural, water soluble and biocompatible polysaccharide, was derivatized by Spermine (Spm), a flexible molecule with four amine groups that, having pKa values in the range between 8-11, is mainly in the protonated form at pH 7.4. The synthesis of related copolymers (Inu-Spm) was performed by a two step reaction, using a method termed Enhanced Microwave Synthesis (EMS) which has the advantage, compared to conventional microwave reaction, that high amount of energy can be applied to the reaction system, by administering microwave irradiation and simultaneously controlling the temperature in the reaction vessel with cooled air. The synthesized inulin derivatives were characterized by FT-IR spectra and 1H-NMR. INU-Spm derivatives with a degree of derivatization of about 14 % mol/mol were obtained. These polycations were tested to evaluate their ability to form non covalent complexes with genetic material (polyplexes). Agarose gel retardation assays showed that the obtained copolymers are able to electrostatically interact with DNA duplex to form polyplexes at different c/p weight ratios. Moreover, light scattering studies, performed to analyze size and z-potential of polyplexes, evidenced that copolymers are able to interact with genetic material leading to the formation of nanoscaled systems. In addition, biocompatibility of polyplexes was demonstrated by performing cytotoxicity assays on a 16HBE cell line. Transfection studies, performed by using siRNA able to silence luciferase expression, demonstrate the efficiency of polyplexes to transfect the same cell line, with a reduction of luciferase expression to about 70%. These results encourage us to work with these copolymers to obtain an efficient and feasible inulin based NABD delivery system
Synthesis and evaluation of thermo-rheological behaviour and ionotropic crosslinking of new gellan gum-alkyl derivatives
No full textThis paper reports the synthesis and the physicochemical characterization of two series of gellan gum (GG) derivatives functionalized with alkyl chains with different number of carbon, from 8 to 18. In particular, low molecular weight gellan gum samples with 52.6 or 96.7 kDa, respectively, were functionalized with octylamine (C8), dodecylamine (C12) and octadecylamine (C18) by using bis(4-nitrophenyl) carbonate (4-NPBC) as a coupling agent. Thermo-rheological and ionotropic crosslinking properties of these gellan gum-alkyl derivatives were evaluated and related to the degree of derivatization in alkyl chains. Results suggested as length and degree of derivatization differently influenced coil-to-helix gelation mechanism of GG derivatives, ionotropic crosslinking, and strength of crosslinked hydrogels obtained in CaCl20.102 M and NaCl 0.15 M. Statement of hypothesis: The insertion of alkyl chains on the gellan gum backbone interferes with coil-to-helix transition mechanism and allows the production of hydrophobically assembled hydrogels
Hyaluronic acid and α-elastin based hydrogel for three dimensional culture of vascular endothelial cells
No full textThe aim of this work was to demonstrate that employing a copolymer of hyaluronic acid and α-elastin (HA-EDA-g-α-elastin) is possible to produce a scaffold able to support the adhesion and growth of human vascular endothelial cells (HUVEC) thanks to its ability to incorporate and control the diffusion of vascular endothelial growth factor (VEGF). HA-EDA-g-α-elastin was crosslinked with low molecular weight hyaluronic acid (HALMW) to obtain a hydrogel that gives rise to the formation of three dimensional sponge after the freeze drying process. The physicochemical features the obtained material along with its ability to act as a support for the three dimensional culture of endothelial cells were here investigated. The obtained hydrogel is able to seize the VEGF and control its release in the first days of incubation. The presence of the growth factor stimulates the proliferation of HUVEC and induces the formation of tubular structures
PREPARAZIONE E CARATTERIZZAZIONE DI NUOVI SCAFFOLD BIOCOMPATIBILI PER APPLICAZIONI NELLA MEDICINA RIGENERATIVA
Full text linkHybrid Gold/Silica/Quantum-Dots supramolecular-nanostructures encapsulated in polymeric micelles as potential theranostic tool for targeted cancer therapy
No full textEfficient theranostic tools are today more and more frequently represented by the nano-sized systems. In this paper, polymeric micelles were produced and exploited to encapsulate both an antitumor drug (Doxorubicin) and gold core–shell quantum dots nanoparticles (Au-SiO2/QDs). α,β-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) was functionalized with lipoic acid (LA), polyethylenglycol (PEG), and folic acid (FA) pendant moieties to obtain a synthetic derivative (PHEA-LA-PEG-FA) able to self assemble in aqueous medium giving rise to the formation of polymeric micelles exposing on their surface both targeting groups (FA) and hydrophilic chains (PEG). The drug carrying ability of PHEA-LA-PEG-FA micelles was here studied along with the cytotoxity of the obtained nanostructures toward breast cancer cells employing doxorubicin as a model anticancer drug. Finally, the properties of the gold-shell QDs incorporated into the micelles as cells imaging agent and photothermal anticancer treatment tool were explored
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