Alginate hydrogels coated with chitosan for wound dressing.

In this work, a coating of chitosan onto alginate hydrogels was realized using the water-soluble hydrochloride form of chitosan (CH-Cl), with the dual purpose of imparting antibacterial activity and delaying the release of hydrophilic molecules from the alginate matrix. Alginate hydrogels with different calcium contents were prepared by the internal setting method and coated by immersion in a CH-Cl solution. Structural analysis by cryo-scanning electron microscopy was carried out to highlight morphological alterations due to the coating layer. Tests in vitro with human mesenchymal stromal cells (MSC) were assessed to check the absence of toxicity of CH-Cl. Swelling, stability in physiological solution and release characteristics using rhodamine B as the hydrophilic model drug were compared to those of relative uncoated hydrogels. Finally, antibacterial activity against Escherichia coli was tested. Results show that alginate hydrogels coated with chitosan hydrochloride described here can be proposed as a novel medicated dressing by associating intrinsic antimicrobial activity with improved sustained release characteristics.

Non-covalent strategies to functionalize polymeric nanoparticles with NGR peptides for targeting breast cancer.

Surface functionalization of nanoparticles (NPs) with tumor-targeting peptides is an emerging approach with a huge potential to translate in the clinic and ameliorate the efficacy of nano-oncologicals. One major challenge is to find straightforward strategies for anchoring peptides on the surface of biodegradable NPs and ensuring their correct exposure and orientation to bind the target receptor. Here, we propose a non-covalent strategy to functionalize polyester aminic NPs based on the formation of either electrostatic or lipophilic interactions between NPs and the peptide modified with an anchoring moiety. We selected an iNGRt peptide containing a CendR motif (CRNGR) targeting neuropilin receptor 1 (NRP-1), which is upregulated in several cancers. iNGRt was linked with either a short poly(glutamic acid) chain (polyE) or a palmitoyl chain (Palm) and used to functionalize the surface of NPs made of a diamine poly(ε-caprolactone). iNGRt-PolyE was adsorbed on preformed cationic NPs through electrostatic interaction, whereas iNGRt-Palm was integrated into the forming NPs through interactions. In both cases, peptides were strongly associated with NPs of ∼100 nm, low polydispersity indexes, and positive zeta potential values. NPs entered MDA-MB231 breast cancer cells overexpressing NRP-1 via receptor-mediated endocytosis and showed a different cell localization depending on the mode of peptide anchoring. When loaded with the lipophilic anticancer drug docetaxel (DTX), NPs functionalized with the iNGRt-Palm variant exerted a time- and dose-dependent cytotoxicity similar to DTX in MDA-MB-231 cells but were less toxic than DTX toward control MRC-5 human fibroblasts, not expressing NRP-1. In a heterotopic mouse model of triple negative breast cancer, iNGRt-Palm NPs were tolerated better than free DTX and demonstrated superior anticancer activity and survival compared to both free DTX and NPs without peptide functionalization. We foresee that the functionalization strategy with palmitoylated peptides proposed here can be extended to other biodegradable NPs and peptide sequences designed for therapeutic or targeting purposes.

Biodegradable nanoparticles combining cancer cell targeting and anti-angiogenic activity for synergistic chemotherapy in epithelial cancer.

A biodegradable engineered nanoplatform combining anti-angiogenic activity and targeting of cancer cells to improve the anticancer activity of docetaxel (DTX) is here proposed. Indeed, we have developed biodegradable nanoparticles (NPs) of poly(ethylene glycol)-poly(ε-caprolactone), exposing on the surface both folate motifs (Fol) for recognition in cells overexpressing Folate receptor-α (FRα) and the anti-angiogenic hexapeptide aFLT1. NPs showed a size around 100 nm, the exposure of 60% of Fol moieties on the surface, and the ability to entrap DTX and sustain its release with time. NPs were stable in simulated biological fluids and slightly interacted with Fetal Bovine serum, especially in the formulation decorated with Fol and aFLT1. The presence of Fol on NPs did not impair the anti-angiogenic activity of aFLT1, as assessed by in vitro tube formation assay in HUVEC endothelial cells. In both 2D and 3D KB cell cultures in vitro, the cytotoxicity of DTX loaded in NPs was not significantly affected by Fol/aFLT1 double decoration compared to free DTX. Remarkably, NPs distributed differently in 3D multicellular spheroids of FRα-positive KB cancer cells depending on the type of ligand displayed on the surface. In particular, NPs unmodified on the surface were randomly distributed in the spheroid, whereas the presence of Fol promoted the accumulation in the outer rims of the spheroid. Finally, NPs with Fol and aFLT1 gave a uniform distribution throughout the spheroid structure. When tested in zebrafish embryos xenografted with KB cells, NPs displaying Fol/aFLT1 reduced DTX systemic toxicity and inhibited the growth of the tumor mass and associated vasculature synergistically. Overall, nanotechnology offers excellent ground for combining therapeutic concepts in cancer, paving the way to novel multifunctional nanopharmaceuticals decorated with bioactive elements that can significantly improve therapeutic outcomes.

Semi-Crystalline Hydrophobic Polyamidoamines: A New Family of Technological Materials?

The hitherto known polyamidoamines (PAAs) are not suitable as structural materials because they are usually water-soluble or swellable in water. This paper deals with the synthesis and characterization of semi-crystalline hydrophobic PAAs (H-PAAs) by combining different bis-sec-amines with bis-acrylamides obtained from C6-C12 bis-prim-amines. H-PAAs were initially obtained in a solution of benzyl alcohol, a solvent suitable for both monomers and polymers. Their number average molecular weights, M¯n, which were determined with 1H-NMR by evaluating the percentage of their terminal units, varied from 6000 to >10,000. The solubility, thermal properties, ignitability and water resistance of H-PAAs were determined. They were soluble in organic solvents, semi-crystalline and thermally stable. The most promising ones were also prepared using a bulk process, which has never been previously reported for PAA synthesis. In the form of films, these H-PAAs were apparently unaffected by water. The films underwent tensile and wettability tests. They showed similar Young moduli (260-263 MPa), whereas the maximum stress and the stress at break depended on the number of methylene groups of the starting bis-acrylamides. Their wettability was somewhat higher than that of common Nylons. Interestingly, none of the H-PAAs considered, either as films or powders, ignited after prolonged exposure to a methane flame.

PEGylated cationic nanoassemblies based on triblock copolymers to combine siRNA therapeutics with anticancer drugs.

Nowadays, the clinical administration of siRNA therapeutics is still challenging due to the need of safe and efficient delivery carriers. In this context, biodegradable and amphiphilic triblock copolymers (ABC) containing amine-based cationic segments could be a powerful tool for siRNA delivery. Herein, we propose a range of poly(ethylene glycol) (PEG)-poly(2-dimethyl(aminoethyl) methacrylate) (pDMAEMA)-polycaprolactone (PCL) copolymers with different lengths of the blocks and hydrophilic/lipophilic balance to deliver siRNA alone or in association with a conventional anticancer drug. mPEG-pDMAEMA-PCL copolymers were synthesized by a combination of techniques and characterized by NMR analysis, Fourier transform infrared (FTIR) spectroscopy, gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Copolymers were then employed to prepare NPs through nanoprecipitation. NPs based on copolymers with long PCL chains (SSL-NPs and LLL-NPs) showed the best colloidal properties and a highly stable core-shell structure with a better orientation of the PEG fringe on the surface. Concerning siRNA delivery, SSL-NPs based on copolymers with short PEG and pDMAEMA chains showed optimized ability to complex and then deliver siRNA at the cell level. The strong interaction between the nucleic acid and the cationic pDMAEMA blocks of NPs was then confirmed by release studies that showed a sustained release of siRNA within 48 h. The transfection efficiency of NPs was assessed in human melanoma cells. NPs were complexed with a therapeutic siRNA against TUBB3 (TUB-siRNA). We observed the best results with SSL-NPs, probably due to the higher preserved buffer capacity of the pDMAEMA blocks. Finally, in order to give a proof of concept of a possible application in the combined chemo/gene-therapy of cancer, SSL-NPs complexed with TUB-siRNA were loaded with docetaxel (DTX) and then cytotoxicity was evaluated in the same cell line. The co-delivery of TUB-siRNA into NPs appeared to strongly potentiate the anti-proliferative activity of DTX, thus highlighting the combinatory activity of the NPs.

Marine polysaccharides in pharmaceutical applications: an overview.

The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest.

Development and performance analysis of PCL/silica nanocomposites for bone regeneration.

In the present article, several developments of biocomposites containing silica nanoparticles intended for bone regeneration are reported. Nanocomposites of poly(ε-caprolactone) (PCL) and silica, in which either the silica nanoparticles or the PCL have been modified in order to improve interfacial adhesion through chemical graft between the phases are hereafter described. The composites are characterized with respect to their chemical-physical and mechanical properties. Their biocompatibility and capacity to induce the osteoblastic phenotype in human bone marrow mesenchymal stem cells have been assessed.

Alginate/human elastin-like polypeptide composite films with antioxidant properties for potential wound healing application.

In this contribution we describe the preparation and characterization of a series of cross-linked films based on the combination of an elastin-derived biomimetic polypeptide (Human Elastin-Like Polypeptide, HELP) with alginate (ALG) to obtain a composite with enhanced properties. ALG/HELP composite films loaded with the hydrophobic natural antioxidant curcumin were prepared by solvent casting method followed by the cross-linking with calcium chloride. The compatibility between the two components as well as the final properties was evaluated. The micro-morphological study of films showed a homogeneous structure, but the film tensile strength decrease with HELP content and elongation at break was adversely affected by biopolymer addition. Spectroscopic and thermal analyses confirmed an interaction between ALG and HELP which also causes a modification in swelling kinetics and faster degradation. Moreover, the study of curcumin release showed a controlled delivery up to 10 days with a faster release rate in the presence of HELP. Human Dermal Fibroblasts (hDF) were used to test the in vitro cytocompatibility. The antioxidant activity correlated to the increase of HELP content suggested the applicability of these composites to develop smart biomaterials. Overall, these features indicated how this composite material has considerable potential as customizable platforms for various biomedical applications.

Zein Beta-Cyclodextrin Micropowders for Iron Bisglycinate Delivery.

Given the limited number of materials available to design delivery platforms for nutrients, the rational combination of raw materials already approved as food ingredients and their processing through nano-micro technology can offer a unique tool for innovation. Here, we propose a nano-in-micro strategy to produce powders based on the hydrophobic protein zein, useful for the oral delivery of a hydrophilic iron source (iron bisglycinate) in anaemic patients. Iron-loaded powders were prepared through a two-step strategy consisting in the formation of a zein pseudolatex followed by a spray-drying step. To extend the manipulation space for zein and entrap iron bisglycinate, ß-cyclodextrin (ßCD) was selected as helping excipient. Addition of ßCD allowed iron loading in the pseudolatex and greatly increased product yields after the drying process as compared to zein alone. Iron-loaded micro-sized powders were characterised by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to elucidate the role of ßCD as a compatibilizer for the zein-iron system. Remarkably, micropowders released only 20% of FeBIS in a simulated gastric fluid, whereas release in a simulated intestinal fluid was almost completed in 7 h. In summary, ßCD association to zein is a novel strategy to expand applications in the oral delivery of iron bisglycinate and, prospectively, to micronutrient chelates.

Surface Exposure of PEG and Amines on Biodegradable Nanoparticles as a Strategy to Tune Their Interaction with Protein-Rich Biological Media.

Nanoparticles (NPs) based on amphiphilic block copolymers of polyethylene glycol (PEG) and biodegradable polyesters are of particular current interest in drug nanodelivery due to their easily manipulated properties. The interaction of these NPs with biological environments is highly influenced by shell features, which drive biological identity after administration. To widen the strategies available for tuning particle surface chemistry, here we developed a panel of amine-bearing PEGylated NPs with a poly(ε-caprolactone) (PCL) core for the delivery of lipophilic drugs, and investigated the impact of NP modifications on their interaction with abundant circulating proteins (human serum albumin-HSA-and mucin), as well as their transport through biological barriers (artificial mucus-AM, extracellular matrix-ECM). We prepared NPs based on a diamino-terminated PCL (amine-NPs) and its mixture with PEG-PCL copolymers (amine/PEG-NPs) at different PEG molecular weights by nanoprecipitation, as well as corresponding NPs of PEG-PCL (PEG-NPs). The presence of an amine-bearing polymer resulted in NPs with a net positive charge and a zeta potential dependent on the length of PEG in the copolymer. Amine/PEG-NPs had a larger fixed aqueous layer thickness as compared to PEG-NPs, suggesting that PEG conformation is affected by the presence of positive charges. In general, amine-bearing NPs promptly interacted with the dysopsonic protein HSA, due to electrostatic interactions, and lose stability, thereby undergoing time-related aggregation. On the other hand, amine/PEG-NPs interaction with mucin induced switching to a negative surface charge but did not alter the quality of the dispersion. The transport kinetics of NPs through a layer of artificial mucus and tumor extracellular matrix was studied by means of fluorescent NPs based upon FRET. Amine/PEG-NPs did not cross the ECM, but they were promptly transported through the AM, with swifter transport noted at increasing MWs of PEG in the copolymer. Finally, we demonstrated that all the different NP types developed in this study are internalized by human monocytes and, despite the positive charge, they did not induce a measurable inflammatory effect. In conclusion, we showed that the concurrent presence of both PEG and amine groups on NP surface is a promising strategy for directing their interaction with body compartments. While PEG-NPs are confirmed for their capacity to cross ECM-like compartments, amine/PEG-NPs are revealed as a powerful platform to widen the arsenal of nanotools available for overcoming mucus-covered epithelia.

Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity.

Inhibition of tumor angiogenesis is considered as a valuable clinical strategy to treat some tumors, although benefits in term of progression-free and overall survival have been modest. Recent findings have pushed toward the use of antiangiogenic drugs in combination with chemotherapy regimens to potentiate therapeutic outcome. Herein, we propose a novel type of biodegradable antiangiogenic core-shell polymeric nanoparticles (NPs) for the delivery of poorly water-soluble chemotherapeutics. An amphiphilic diblock copolymer of poly(ethyleneglycol)-poly(ε-caprolactone) (PEG-PCL) was conjugated with an anti-FLT1 hexapeptide (aFLT1) at -OH PEG end, mixed in appropriate ratios with a monomethoxy-PEG-PCL and nanoprecipitated to form core-shell aFLT1-bearing NPs (DBLaFLT1). DBLaFLT1 were <100 nm, exposed aFLT1 on the surface and showed a higher thickness of the external hydrophilic shell as compared to NPs that do not bear aFLT1 (DBL). Very interestingly, DBLaFLT1 showed an antiangiogenic activity in the human umbilical endothelial cells (HUVEC) tube formation assay three-fold higher than an equivalent dose of free aFLT1. To provide a proof-of-concept of DBLaFLT1 potential in the delivery of conventional chemotherapeutics, docetaxel (DTX) was selected as model drug. DBLaFLT1 entrapped DTX with high efficiency and sustained its release along time in simulated biological conditions. At a non-cytotoxic dose, DTX-loaded DBLaFLT1 almost completely abolished tube formation in HUVEC while inhibition of DTX loaded DBL was significantly lower. The cytotoxicity of DTX-loaded NPs in HUVEC and triple negative breast cancer cells (MDA-MB-231) was not significantly different from that of the free drug in a wide range of concentrations and up to 72 h. Studies carried out in MDA-MB-231 cells implanted in chicken embryo chorioallantoic membranes (CAMs) evidenced an antiangiogenic activity of DTX-loaded DBLaFLT1 higher as compared with that of both DTX-loaded DBL and free DTX. While cancer cell migration from the tumor site was unaffected, the anticancer activity of DTX-loaded NPs was higher than that of free DTX and maximized for DTX-DBLaFLT1. In perspective, these results suggest that the delivery approach proposed here can be applied to other lipophilic chemotherapeutics devoid of relevant antiangiogenic properties to improve the final therapeutic response.

Compatibilized polymer blends based on PDLLA and PCL for application in bioartificial liver.

Porous scaffolds for tissue engineering applications based on poly(D,L-lactide)/poly(epsilon-caprolactone) compatibilized blends are described. The addition of a third polymer, namely poly( D, L-lactide-co-caprolactone) copolymer, has a profound effect on morphological properties of the blends scaffolds. In fact, the copolymer acts as compatibilizing agent and reduces the dimension of the dispersed phase of an order of magnitude. Such effect is function of the polymer composition. The efficiency of scaffolds obtained with poly( D, L-lactide) based blends containing 30% by weight of poly(epsilon-caprolactone) as dispersed phase toward hepatocytes has been tested by several biological assays and we found that they are able to promote a perfect adhesion, proliferation and growth of cells. Moreover, the addition of the copolymer significantly improves the biomedical performance of the scaffold.

Marine derived polysaccharides for biomedical applications: chemical modification approaches.

Polysaccharide-based biomaterials are an emerging class in several biomedical fields such as tissue regeneration, particularly for cartilage, drug delivery devices and gelentrapment systems for the immobilization of cells. Important properties of the polysaccharides include controllable biological activity, biodegradability, and their ability to form hydrogels. Most of the polysaccharides used derive from natural sources; particularly, alginate and chitin, two polysaccharides which have an extensive history of use in medicine, pharmacy and basic sciences, and can be easily extracted from marine plants (algae kelp) and crab shells, respectively. The recent rediscovery of poly-saccharidebased materials is also attributable to new synthetic routes for their chemical modification, with the aim of promoting new biological activities and/or to modify the final properties of the biomaterials for specific purposes. These synthetic strategies also involve the combination of polysaccharides with other polymers. A review of the more recent research in the field of chemical modification of alginate, chitin and its derivative chitosan is presented. Moreover, we report as case studies the results of our recent work concerning various different approaches and applications of polysaccharide-based biomaterials, such as the realization of novel composites based on calcium sulphate blended with alginate and with a chemically modified chitosan, the synthesis of novel alginate-poly(ethylene glycol) copolymers and the development of a family of materials based on alginate and acrylic polymers of potential interest as drug delivery systems.

Biodegradable nanoparticles bearing amine groups as a strategy to alter surface features, biological identity and accumulation in a lung metastasis model.

Polymer-based nanoparticles (NPs) with a cationic charge have emerged recently as a potent nanotool due to their unique ability to penetrate deeply inside tumor tissue and to interact preferentially with the plasma membrane of cancer cells. In this paper, we propose a general strategy to obtain biodegradable cationic NPs of poly(ε-caprolactone) (PCL) based on an amine terminated PCL (NH2-PCL4.2k) or its mixture with monomethoxypoly(ethylene glycol)-PCL (mPEG1k-PCL4k). Positively-charged NPs were obtained, switching to net negative values through adsorption of low molecular weight hyaluronan. NPs exposing both amine and PEG groups on the surface showed a larger fixed aqueous layer thickness as compared to fully PEGylated NPs, suggesting that PEG conformation/localization is affected by the presence of amino groups. The stability of the positively-charged NPs was affected by the presence of ions, while interaction with the human plasma protein pool indicated time-dependent protein corona formation imparting an overall negative charge. NP-induced haemolysis was low, while cytotoxicity against A549 and Calu-3 lung cancer cell lines was cell-specific as well as dose and time-dependent. Finally, the presence of amino groups greatly changed the in vivo biodistribution of the NPs in tumor-bearing mice (lung colonization of B16F10 cancer cells) allowing the amine/PEGylated NPs to accumulate mainly at the target organ. Overall, this study demonstrates that NPs with a mixed amine/PEGylated surface exhibit a peculiar biological identity that alters their interaction with the bioenvironment and are thus worthy of further investigation in the delivery of chemotherapeutics.

Correction: Biodegradable nanoparticles bearing amine groups as a strategy to alter surface features, biological identity and accumulation in a lung metastasis model.

Correction for 'Biodegradable nanoparticles bearing amine groups as a strategy to alter surface features, biological identity and accumulation in a lung metastasis model' by Diletta Esposito et al., J. Mater. Chem. B, 2018, 6, 5922-5930.

Macroporous alginate foams crosslinked with strontium for bone tissue engineering.

Nowadays, the need of novel strategies to repair and regenerate bone defects in the field of biomedical applications has increased. Novel approaches include the design of natural bioactive scaffolds mimicking bone tissue. These bioactive scaffolds have to possess biophysical properties suitable to address biological response towards newly bone tissue formation. In particular, scaffold porosity and pore size play a pivotal role in cell migration, adhesion and proliferation, thus increasing cell-material surface interaction and osteogenic signals transmission. Here we propose the development of macroporous alginate foams (MAFs) with porous and well interconnected structure, useful to enhance growth and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). Moreover, in this study we report a new method for MAFs fabrication based on the combination of internal gelation technique with gas foaming. Strontium was employed in combination with calcium as cross-linking agent for the alginate chains and as enhancer of the osteogenic differentiation. The influence of strontium ions on the gelation kinetics, physical properties and degradation in physiological medium of MAFs was investigated. Our results suggest that the combination of internal gelation technique with gas foaming followed by freeze-drying is an easy and straightforward procedure to prepare alginate foams with high porosity and interconnectivity, able to support cell infiltration. Finally, biological assays showed how scaffolds with high strontium content are able to support cell growth and differentiation in long times by promoting osteogenic marker expression.

Shedding light on surface exposition of poly(ethylene glycol) and folate targeting units on nanoparticles of poly(ε-caprolactone) diblock copolymers: Beyond a paradigm.

Polymeric nanoparticles (NPs) of poly(ε-caprolactone) (PCL) covered with a hydrophilic poly(ethylene glycol) (PEG) shell are usually prepared from diblock PEG-PCL copolymers through different techniques. Furthermore PEG, NPs can be decorated with targeting ligands to accumulate in specific cell lines. However, the density and conformation of PEG on the surface and its impact on the exposition of small targeting ligands has been poorly considered so far although this has a huge impact on biological behaviour. Here, we focus on PEG-PCL NPs and their folate-targeted version to encourage accumulation in cancer cells overexpressing folate receptor α. NPs were prepared with mixtures of PEG-PCL with different PEG length (short 1.0kDa, long 2.0kDa,) and a folate-functionalized PEG-PCL (PEG 1.5kDa) by the widely employed solvent displacement method. In depth characterization of NPs surface by 1H NMR, fluorescence and photon correlation spectroscopy evidenced a PEGylation extent below 7% with PEG in a mushroom conformation and the presence of folate more exposed to water pool in the case of copolymer with short PEG. NPs with short PEG adsorbed HSA forming a soft corona without aggregating. Although limited, PEGylation overall reduced NPs uptake in human macrophages. Uptake of NPs exposing folate prepared with short PEG was higher in KB cells (FR+) than in A549 (FR-), occurred via FR-receptor and involved lipid rafts-dependent endocytosis. In conclusion, the present results demonstrate that PEG length critically affects protein interaction and folate exposition with a logical impact on receptor-mediated cell uptake. Our study highlights that the too simplistic view suggesting that PEG-PCL gives PEG-coated NPs needs to be re-examined in the light of actual surface properties, which should always be considered case-by-case.

Development of a new calcium sulphate-based composite using alginate and chemically modified chitosan for bone regeneration.

In this work we developed a novel calcium sulphate-based composite in which the hemihydrate calcium sulphate (CHS) can be encapsulated in a polymeric biodegradable and biocompatible matrix, in order to retain the structural integrity and decrease the bioresorption rate in bone regeneration applications. Two polymers were employed to realize this system: chitosan (Ch) and sodium alginate (Alg), both already widely used in biotechnological and biomedical applications. Chitosan was modified in order to obtain a water soluble polymer, the N-succinylchitosan (sCh). The reaction was performed with succinic anhydride in presence of pyridine and confirmed by FT-IR and NMR analyses. Finely ground Alg and sCh powders were mixed in different compositions with CHS and by adding water to the powder mixture it was obtained a mouldable paste that sets in few hours. Thermogravimetric analyses coupled with solvent extraction performed on the composite proved the alginate crosslinking in the presence of CHS. Mechanical studies carried out on composites of different compositions demonstrated that the blend of the two polymeric components causes a substantial synergistic reinforcement of composites. The presence of carboxylic groups on sCh chain in addition to those of alginate could enhance the chelating power of polysaccharide mixture. The results obtained with morphological analyses (SEM) further confirmed the hypotesis of the synergistic effect between alginate and N-succinylchitosan in presence of calcium sulphate. In vitro cytotoxicity tests proved that the developed system was not cytotoxic.

Novel alginate-acrylic polymers as a platform for drug delivery.

The aim of the present work was to develop a family of novel materials based on a combination of sodium alginate and acrylic polymers and to evaluate their potential in drug delivery applications. In the presence of sodium alginate, acrylic chains with acidic as well as basic moieties were polymerized to create an interpolymer complex based on electrostatic interactions that are able to modulate the release rate of low molecular weight drugs. The synthesized materials were used to prepare hydrophilic matrices for drug delivery and tested for their adhesion properties to glass, used as a model substrate for mucoadhesion.