186,631 research outputs found
Linear Polyamidoamines as Novel Biocompatible Intumescent Flame Retardants for Cotton
No full textSince the middle of the last century, many industrial and academic researchers have devoted a lot of effort to the development of safe and effective flame- retardants (FR). As regards cotton, phosphorylated compounds were the predominant FR for several decades [1] despite many of them had been shown to be bioaccumulative.[1] Recently, biomolecules including proteins have been proposed as FR.[2] Many linear polyamidoamines (PAAs), a family of synthetic polymers with exceptional structural versatility,[3] have high thermal stability coupled with chain structure and side substituents reminding those of proteins.[4] These features suggested that PAAs could act as FR. This presentation reports on the results obtained with a library of eight PAAs applied as coatings on cotton fabrics from aqueous solutions. All tested PAAs warrant remarkable potential as surface-confined intumescent FR. In ignitability tests, six of them exposed to direct flame for 10 s do not burn, but produce carbonaceous crusts sheltering the underneath sample. Thermogravimetric analyses show that at T ≥ 400 °C all PAAs leave in air substantial char residues that oxidize at T > 500 °C. At 450 °C they form porous carbonaceous structures indicating the tendency to intumesce. In horizontal flame spread tests, cotton stripes impregnated with most PAAs extinguish flame at add-ons ranging from 4 to 20%, whereas untreated cotton vigorously burns without leaving residues. Upon 35 kW/m2 heat flux, all PAA-treated samples significantly reduce the main combustion parameters.
References
[1] R. A. Horrocks, Polym. Degrad. Stab. 2011, 96, 377.
[2] L. Costes, F. Laoutid, S. Brohez, P. Dubois, Mater. Sci. Eng. Report, R. 2017, 117, 1.
[3] P. Ferruti, J. Polym. Sci, Part A: Polym. Chem. 2013, 51, 2319.
[4] F. Danusso, P. Ferruti, Polymer 1970, 11, 88
Poly(amidoamine) Conjugates Containing Doxorubicin Bound via an Acid-Sensitive Linker.
No full textPoly(amidoamine)s with amino pendant groups were prepared by hydrogen-transfer polyaddition of primary and secondary amines to bis-acrylamines. Dansyl cadaverine (DC) doxorubicin (Dox) were bound to the polymers via a cis-aconityl spacer to give conjugates containing 3 µg of DC per mg of polymer and 28 to 35 µg of Dox per mg of polymer. Release of DC and Dox at physiological and acidic pH varied from 0 to 35% over 48 h and was pH dependent. Although the ISA1Dox conjugate (IC50 = 6 µg Dox · mL-1) presented similar toxicity as the parent polymer without Dox, ISA23Dox showed increased toxicity (IC50 = 10 µg Dox · mL-1). These results suggest that ISA23Dox is able to release biologically active Dox in vitro and that this conjugate might be suitable for further development
Poly(amido-amine)s as carriers for intracellular delivery of drugs and proteins
No full textPolyamidoamines (PAAs) are synthetic polymers carrying amide- (a) and tert-amine (b) groups regularly arranged along the polymer chain according to the sequences …a…a…b…b… or …a…a…b…. They are prepared by Michael polyaddition of primary or secondary amines to bisacrylamides (Scheme 1) (Danusso and Ferruti, 1970; Ferruti, 1996; Ferruti et al., 1985). The PAAs are endowed with a combination of properties that make them appealing for practical applications, particularly in the biotechnological field
Poly(amidoamine)s : past, present, and perspectives
No full textA review. Poly(amidoamine)s (PAAs) are a family of synthetic polymers obtained by stepwise polyaddn. of prim- or sec-amines to bisacrylamides. Nearly all conceivable bisacrylamides and prim- or sec-amines can be employed as monomers endowing PAAs of a structural versatility nearly unique among stepwise polyaddn. polymers. PAAs are degradable in aq. media, including physiol. fluids. Many of them are remarkably biocompatible notwithstanding their cationic character. PAAs are per se highly functional polymers and, in addn., can be further functionalized giving rise to an endless variety of polymeric structures meeting the requisites for applications in such apparently disparate fields as inorg. water pollutants scavengers, sensors, drug and protein intracellular carriers, transfection promoters, peptidomimetic antiviral and antimalarial agents. In this review, the unique chem. of PAAs is discussed and a vast library of PAA structures and PAA applications from the beginning to the present days reported
Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo
No full textLinear poly(amidoamine)s (PAAs) have been designed to exhibit minimal non-specific toxicity, display pH-dependent membrane lysis and deliver genes and toxins in vitro. The aim of this study was to measure PAA cellular uptake using ISA1-OG (and as a reference ISA23-OG) in B16F10 cells in vitro and, by subcellular fractionation, quantitate intracellular trafficking of (125)I-labelled ISA1-tyr in liver cells after intravenous (i.v.) administration to rats. The effect of time after administration (0.5-3h) and ISA1 dose (0.04-100mg/kg) on trafficking, and vesicle permeabilisation (N-acetyl-b-D-glucosaminidase (NAG) release from an isolated vesicular fraction) were also studied. ISA1-OG displayed approximately 60-fold greater B16F10 cell uptake than ISA23-OG. Passage of ISA1 along the liver cell endocytic pathway caused a transient decrease in vesicle buoyant density (also visible by TEM). Increasing ISA1 dose from 10mg/kg to 100mg/kg increased both radioactivity and NAG levels in the cytosolic fraction (5-10 fold) at 1h. Moreover, internalised ISA1 provoked NAG release from an isolated vesicular fraction in a dose-dependent manner. These results provide direct evidence, for the first time, of PAA permeabilisation of endocytic vesicular membranes in vivo, and they have important implications for potential efficacy/toxicity of such polymeric vectors
Probing chiral interactions between L- and D-arginine-based polymers and sodium deoxycholate solutions
No full textNowadays the spontaneous self-organization of a polymer into an ordered structure is a soughtafter property of many smart materials, whose applications might range from catalysis [1] to drugdelivery [2]. However, literature regarding the role played by these specific conformations in chiral recognition remains scarce. In this context, polyamidoamino acids (PAACs) are an emerging class of stimuli-responsive bioinspired synthetic polymers able to self-assemble into pH depend conformations [3,4]. PAACs are an off-spring of polyamidoamines (PAAs), a family of polymers obtained by the Michael-type polyaddition of prim-monoamines or sec-diamines with bisacrylamides. The reaction occurs in aqueous solution at pH = 8–9 and at room temperature. By using α-amino acids as monomers, PAACs are obtained.
The first example of PAAC was named ARGO7, obtained by the stepwise polyaddition in water of L- or D-arginine to N,N’-methylenebisacrylamide. Results indicated Mn 8500, PDI 1.4 and Rh of 1.2 nm [3]. Molecular dynamics (MD) and circular dichroism (CD) showed ARGO7 folded into a rigid structure, reminiscent of the hairpin conformation, solely driven by the polymer main chain. Due to its ability to self-assemble in solution forming chiral structures, L- and D-ARGO7 may selectively interact with biological components.
To assess chiral recognition, sodium deoxycholate (NaDC), one of the components of bile salts, was chosen as a chiral model surface. In aqueous solution, NaDC showed three different pH dependent behaviour: homogeneous solution (pH>8), gel phase (pH 7-8) and aggregation/flocculation (pH<6.5). Notwithstanding the ability of NaDC to self-assemble into different conformations at each pH interval, signs of chiral recognition were found in NaDC gel phase only. Conformational modifications were probed by circular dichroism spectroscopy: both D- and L-ARGO7 changed shape and magnitude of the CD pattern, whereas D,L-ARGO7 did not modify the CD spectra of NaDC. After 8 days, NaDC compact structure loosened, ended up being fluid and the CD pattern were completely modified due to NaDC and D- or L-ARGO7 interactions. Incoming diffusion NMR and SANS studies will probably highlight the mechanisms and dynamics of the chiral interactions in these polyelectrolyte-micelle systems.
[1] Luo, R.; Zhu, M.; Shen, X.; Li, S. J. Catal. 2015, 331, 49. [2] Quiñones, J. P.; Peniche, H.; Peniche, C. Polymers. 2018, 10, 3, 235. [3] Manfredi, A.; Mauro, N.; Terenzi, A.; Alongi, J.; Lazzari, F.; Ganazzoli, F.; Raffaini, G.; Ranucci, E.; Ferruti, P. ACS Macro Lett. 2017, 6, 987. [4] Lazzari, F.; Manfredi, A.; Alongi, J.; Mendichi, R.; Ganazzoli, F.; Raffaini, G.; Ferruti, P.; Ranucci, E. Polymers 2018, 10, 1261
Chiral recognition in D-, L-arginine derived polyamidoamino acids and sodium deoxycholate solutions
No full textNowadays the spontaneous self-organization of a polymer into an ordered structure is a sought-after property of many smart materials, whose applications might range from catalysis1 to drug-delivery2. However, literature regarding the role played by these specific conformations in chiral recognition remains scarce. In this context, polyamidoamino acids (PAACs) are an emerging class of stimuli-responsive bioinspired synthetic polymers able to self-assemble into pH depend conformations.3,4 Arginine based PAACs, named ARGO7, were obtained in water at pH 8-9 from the stepwise polyaddition of L- or D-arginine to N,N’methylenebisacrylamide. Results indicated Mn 8500, PDI 1.4 and Rh of 1.2 nm.3 Molecular dynamics (MD) and circular dichroism (CD) showed ARGO7 folded into a rigid structure, reminiscent of the hairpin conformation, solely driven by the polymer main chain. Due to its ability to self-assemble in solution forming chiral structures, L- and D-ARGO7 may selectively interact with biological components. To assess chiral recognition, sodium deoxycholate (NaDC), one of the components of bile salts, was chosen as a chiral model surface. In aqueous solution, NaDC showed three different pH dependent behaviour: homogeneous solution (pH>8), gel phase (pH 7-8) and aggregation/flocculation (pH<6.5). Notwithstanding the ability of NaDC to self-assemble into different conformations at each pH interval, signs of chiral recognition were found in NaDC gel phase only. Conformational modifications were probed by circular dichroism spectroscopy: both D- and L-ARGO7 changed shape and magnitude of the CD pattern, whereas D,LARGO7 did not modify the CD spectra of NaDC. After 8 days, NaDC compact structure loosened, ended up being fluid and the CD pattern were completely modified due to NaDC and D- or L-ARGO7 interactions. Incoming SANS studies will probably highlight the mechanisms and dynamics of the chiral interactions in these polyelectrolyte-micelle systems.
(1) Luo, R.; Zhu, M.; Shen, X.; Li, S. J. Catal. 2015, 331, 49. (2) Quiñones, J. P.; Peniche, H.; Peniche, C. Polymers. 2018, 10, 3, 235. (3) Manfredi, A.; Mauro, N.; Terenzi, A.; Alongi, J.; Lazzari, F.; Ganazzoli, F.; Raffaini, G.; Ranucci, E.; Ferruti, P. ACS Macro Lett. 2017, 6, 987. (4) Lazzari, F.; Manfredi, A.; Alongi, J.; Mendichi, R.; Ganazzoli, F.; Raffaini, G.; Ferruti, P.; Ranucci, E. Polymers 2018, 10, 1261
Synthesis and endosomolytic properties of poly(amidoamine) block copolymers
No full textThe poly(amidoamine)s (PAAs) ISA 1 and ISA 23 display pH-dependent conformational change and pH-dependent membrane perturbation. These properties confer potential for use as endosomolytic polymers for intracytoplasmic delivery of toxins and genes. Both polymers are relatively non-toxic, and moreover ISA 23 has the beneficial property in vivo, of being non hepatotropic when administered intravenously. Although ISA 23 and ISA 1 demonstrate ability to transfect cells, ISA 1 is also able to promote intracellular delivery of non-permeant toxins. The aim of this study was to synthesise random and block copolymers of ISA 1 and ISA 23 and investigate whether these second generation hybrids would allow optimisation of PAA biological characteristics. Random and block copolymers of ISA 1 and ISA 23 were synthesised by hydrogen transfer polyaddition to generate a library of PAAs with an ISA 23:ISA 1 molar ratios of 2:1 to 4: 1. The resultant polymers have a pI slightly below 7.4 and a (M) over bar (w) of 19900-49000 g/mol and a (M) over bar (n) of 13100-24100 g/mol. Whereas none of the random or block copolymers were haemolytic at pH 7.4 all demonstrated pH-dependent membrane activity. At pH 5.5 they caused 50-60% haemoglobin (Hb) release over 1 h. This was slightly less than that seen for ISA 23 (80% Hb release). None of the copolymers were cytotoxic against B16F10 cells during a 72 h incubation (IC50 > 2 mg/ml; MTT assay). The ability of the random and block copolymer PAAs to deliver the toxin gelonin was also examined, but only ISA 1 and the block copolymer B2 (ISA 23:ISA 1 at a 2:1 molar ratio) were able to promote intracellular delivery, as measured by cytotoxic activity. It would be interesting to study the body distribution of B2 and determine whether this toxin-delivering PAA is able to escape liver capture
Biodegradable hydrogels as scaffolds for nerve regeneration
No full textBiodegradable hydrogels as scaffolds for nerve regeneration
Valerio Magnaghi 1, Elisabetta Ranucci 2, Fabio Fenili 2, Patrizia Procacci 3, Giorgio Pivato 4, Paolo Cortese 4 and Paolo Ferruti 2
1 Department of Endocrinology, Physiopathology, Applied biology, Via Balzaretti 9, University of Milan, 20133 Milan, Italy
2 Department of Organic and Industrial Chemistry, University of Milan, Via Venezian 21, 20133 Milan, Italy
3 Department of Human Morphology and Biomedical Sciences - Citta' Studi, University of Milan, Via Mangiagalli 31, 20133 Milan, Italy
4 Hand Surgery Unit, IRCCS Multimedica, Via Milanese 300, 20099 Sesto San Giovanni, Italy
Transected peripheral nerves are typically reconnected by direct end-to-end surgery or by autologous nerve graft. However, artificial synthetic guide are a successful alternative which may prevent neuroma formation (1). Among biodegradable conduits a novel approach is represented by use of tuneable polyamidoamine (PAA)-based hydrogels, with specific diameters, different shapes and/or dimensions. Depending by their crosslinking degree, hydrogels made by PAAs are tough material which may absorb large amounts of water. PAA hydrogels are biocompatible and biodegradable in vitro to non-toxic low molecular weight products over a period of time varying from few weeks to months (2). In order to evaluate their ability to promote nerve regeneration, PAA hydrogels scaled as scaffold conduits (10mm lenght, 1mm internal diameter) were studied by using an experimental model of rat nerve transection. A conduit was used to join a gap of 4-5 mm in the sciatic nerve, and a longitudinal analysis was made at 30, 45, 60, 90 days post-surgery. We performed the gait analysis to evaluate locomotor coordination, the plantar test to study nociception and pain sensitivity, and the morphological-morphometric analysis to evaluate the nerve recovery. Preliminary results indicate that nerve ends can be successfully joined by these PAA-based hydrogel conduits. One month after surgery, in fact, the regeneration is appreciable inside the conduit and the nerve is resistant to mechanical traction, without signs of inflammation or serum infiltrate. In the implanted rats 45 days after surgery the footprints analysis reveals a trail similar to sham-operated animals, while the thermal hypersensitivity tend to normalize to the control levels at later times. The morphological evaluation of the explanted conduit at 90 days after surgery shows normal myelin structures, confirming nerve regeneration and complete scaffold re-absorption. In conclusion, our results demonstrate that PAA hydrogels might be a promising scaffold tube for nerve regeneration. Further studies on the hydrogels functionalization for drug delivery, with growth factors or hormones, are in progress in our labs.
References
1. Yannas, I.V., Hill, B.J., 2004. Selection of biomaterials for peripheral nerve regeneration using data from the nerve chamber model. Biomaterials 25, 1593-1600.
2. Jacchetti, E., Elimitri, E., Rodighiero, S., Indrieri, M., Gianfelice, A., Lenardi, C., Podestà, A., Ranucci, E., Ferruti, P. Milani, P., 2008. P. Biomimetic poly(amidoamine) hydrogels as synthetic materials for cell culture. J. Biothecnol. 6, 1
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