Cationic Pullulan Derivatives Based Flocculants for Removal of Some Metal Oxides from Simulated Wastewater.

Modified polysaccharides have been increasingly used as flocculants in wastewater treatment due to their non-toxicity, low price, biodegradability, etc. However, the pullulan derivatives are less used in wastewater purification processes. Therefore, this article presents some data regarding FeO and TiO2 particle removal from model suspensions by some pullulan derivatives with pendant quaternary ammonium salt groups, trimethylammonium propyl carbamate chloride (TMAPx-P). The influence of the polymer ionic content, dose, and initial solution concentration as well as of the dispersion pH and composition (metal oxide content, salts, and kaolin) on the separation efficacy were considered. UV-Vis spectroscopy measurements have shown a very good removal efficacy of TMAPx-P for the FeO particles (around 95% and more), irrespective of the polymer and suspension characteristics; a lower clarification of the TiO2 particles suspension (removal efficiency between 68% and 75%) was noticed. Both the zeta potential and the particle aggregates size measurements revealed the charge patch as the main mechanism which governs the metal oxide removal process. The surface morphology analysis/EDX data provided supplementary evidence regarding the separation process. A good removal efficiency (90%) of the pullulan derivatives/FeO flocs for the Bordeaux mixture particles from simulated wastewater was found.

Removal of the commercial pesticides Novadim Progress, Bordeaux mixture and Karate Zeon by pullulan derivatives based flocculants.

Cationic pullulan derivatives have been synthesized and evaluated, for the first time, as flocculants for the separation of the commercial pesticides, Novadim Progress (organophosphoric type), Bordeax mixture and Karate Zeon (pyrethroid type) from synthetic wastewater. The investigated polymer samples contained either pendent tertiary amine or quaternary ammonium salts groups. The separation efficiency was followed by UV-Vis spectroscopy, while the information regarding the mechanism involved in the separation of pesticide particles have been obtained by zeta potential. UV-Vis spectroscopy data showed strong pesticide particles/polycation interactions in case of Novadim Progress and Bordeaux mixture (maximum pesticide removal between 90% and 98%). Good separation efficiency (around 80%) of Karate Zeon emulsion was also noticed. The zeta potential measurements indicated that the charge neutralization was the common flocculation mechanism for the removal of these pesticides. In addition, the hydrogen bondings and chelation of copper ions by amide and/or tertiary amino groups of the polycations had a noteworthy contribution to the pesticide removal.

Chitosan-Oxidized Pullulan Hydrogels Loaded with Essential Clove Oil: Synthesis, Characterization, Antioxidant and Antimicrobial Properties.

Emulsion hydrogels are promising materials for encapsulating and stabilizing high amounts of hydrophobic essential oils in hydrophilic matrices. In this work, clove oil-loaded hydrogels (CS/OP-C) are synthesized by combining covalent and physical cross-linking approaches. First, clove oil (CO) was emulsified and stabilized in a chitosan (CS) solution, which was further hardened by Schiff base covalent cross-linking with oxidized pullulan (OP). Second, the hydrogels were subjected to freeze-thaw cycles and, as a result, the clove oil was stabilized in physically cross-linked polymeric walls. Moreover, due to cryogelation, the obtained hydrogels exhibited sponge-like porous interconnected morphology (160-250 µm). By varying the clove oil content in the starting emulsion and the degree of cross-linking, the hydrogels displayed a high water retention capacity (swelling ratios between 1300 and 2000%), excellent elastic properties with fast shape recovery (20 s) after 70% compression, and controlled in vitro clove oil release in simulated skin conditions for 360 h. Furthermore, the prepared clove oil-loaded hydrogels had a strong scavenging activity of 83% and antibacterial and antifungal properties, showing a bacteriostatic effect after 48 and 72 h against S. aureus and E. coli. Our results recommend the new clove oil-embedded emulsion hydrogels as promising future materials for application as wound dressings.

Composite Hydrogels with Embedded Silver Nanoparticles and Ibuprofen as Wound Dressing.

The wound healing process is often slowed down as a result of complications from bacterial infections and inflammatory reactions. Therefore, it is necessary to develop dressings with fast antibacterial and anti-inflammatory activity that shorten the wound healing period by promoting cell migration and proliferation. Chitosan (CS)-based hydrogels have been widely studied for their antibacterial and wound healing capabilities. Herein, we developed a composite hydrogel based on CS and PVA embedding silver nanoparticles (AgNPs) with antibacterial properties and ibuprofen (Ib) as an anti-inflammatory agent. The hydrogel prepared by double physical cross-linking, with oxalic acid and by freeze-thawing, loaded with 0.225 wt.% AgNPs and 0.264 wt.% Ib, displayed good mechanical properties (compressive modulus = 132 kPa), a high swelling degree and sustained drug delivery (in simulated skin conditions). Moreover, the hydrogel showed strong antibacterial activity against S. aureus and K. pneumoniae due to the embedded AgNPs. In vivo, this hydrogel accelerated the wound regeneration process through the enhanced expression of TNF alpha IP8, by activating downstream cascades and supporting the healing process of inflammation; Cox2, which enhances the migration and proliferation of cells involved in re-epithelization and angiogenesis; MHCII, which promotes immune cooperation between local cells, eliminating dead tissue and controlling infection; the intense expression of Col I as a major marker in the tissue granulation process; and αSMA, which marks the presence of myofibroblasts involved in wound closure and indicates ongoing re-epithelization. The results reveal the potential healing effect of CS/PVA/AgNPs/Ib hydrogels and suggest their potential use as wound dressings.

Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications.

The therapeutic efficiency of plant extracts has been limited by their poor pharmaceutical availability. Hydrogels have promising potential to be applied as wound dressings due to their high capacity to absorb exudates and their enhanced performance in loading and releasing plant extracts. In this work, pullulan/poly (vinyl alcohol) (P/PVA) hydrogels were first prepared using an eco-friendly method based on both a covalent and physical cross-linking approach. Then, the hydrogels were loaded with the hydroalcoholic extract of Calendula officinalis by a simple post-loading immersion method. Different loading capacities were investigated in terms of the physico-chemical properties, chemical composition, mechanical properties, and water absorption. The hydrogels exhibited high loading efficiency due to the hydrogen bonding interactions between polymer and extract. The water retention capacity as well as the mechanical properties decreased with the increase in the extract amount in hydrogel. However, higher amounts of extract in the hydrogel improved the bioadhesiveness. The release of extract from hydrogels was controlled by the Fickian diffusion mechanism. Extract-loaded hydrogels expressed high antioxidant activity, reaching 70% DPPH radical scavenging after 15 min immersion in buffer solution at pH 5.5. Additionally, loaded hydrogels showed a high antibacterial activity against Gram-positive and Gram-negative bacteria and were non-cytotoxic against HDFa cells.

Poloxamer/Carboxymethyl Pullulan Aqueous Systems-Miscibility and Thermogelation Studies Using Viscometry, Rheology and Dynamic Light Scattering.

Thermally-induced gelling systems based on Poloxamer 407 (PL) and polysaccharides are known for their biomedical applications; however, phase separation frequently occurs in mixtures of poloxamer and neutral polysaccharides. In the present paper, the carboxymethyl pullulan (CMP) (here synthesized) was proposed for compatibilization with poloxamer (PL). The miscibility between PL and CMP in dilute aqueous solution was studied by capillary viscometry. CMP with substitution degrees higher than 0.5 proved to be compatible with PL. The thermogelation of concentrated PL solutions (17%) in the presence of CMP was monitored by the tube inversion method, texture analysis and rheology. The micellization and gelation of PL in the absence or in the presence of CMP were also studied by dynamic light scattering. The critical micelle temperature and sol-gel transition temperature decrease with the addition of CMP, but the concentration of CMP has a peculiar influence on the rheological parameters of the gels. In fact, low concentrations of CMP decrease the gel strength. With a further increase in polyelectrolyte concentration, the gel strength increases until 1% CMP, then the rheological parameters are lowered again. At 37 °C, the gels are able to recover the initial network structure after high deformations, showing a reversible healing process.

Tri-Component Hydrogel as Template for Nanocrystalline Hydroxyapatite Deposition Using Alternate Soaking Method for Bone Tissue Engineering Applications.

Composite hydrogels containing apatite-like particles can act as scaffolds for osteoblast proliferation, with applications in bone tissue engineering. In this respect, porous biocompatible hydrogels were obtained from chitosan, oxidized pullulan, and PVA in different ratios. The stability of the hydrogels was ensured both by covalent bonds between aldehyde groups of oxidized pullulan and free amino groups of chitosan, and by physical bonds formed during freeze-thaw cycles and lyophilization. The deposition of calcium phosphates was performed by alternate soaking of the porous hydrogels into solutions with calcium and phosphate ions, assuring a basic pH required for hydroxyapatite formation. The mineralized hydrogels were characterized using FTIR spectroscopy, scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis, showing that inorganic particles containing between 80 and 92% hydroxyapatite were deposited in a high amount on the pore walls of the polymeric matrix. The composition of the organic matrix influenced the crystallization of calcium phosphates and the mechanical properties of the composite hydrogels. In vitro biological tests showed that mineralized hydrogels support the proliferation of MG-63 osteoblast-like cells to a greater extent compared to pristine hydrogels.

Grafted Pullulan Derivatives for Reducing the Content of Some Pesticides from Simulated Wastewater.

The goal of the current article was to obtain data regarding the application of a series of grafted pullulan derivatives, as flocculating agents, for removal of some pesticide formulations from model wastewater. The pullulan derivatives are cationic polyelectrolytes, with various content and length of grafted poly[(3-acrylamidopropyl)-trimethylammonium chloride] chains onto the pullulan (P-g-pAPTAC)]. The commercial pesticides are either fungicide (Bordeaux Mixture) (BM) or insecticides (Decis (Dc)-active ingredient Deltamethrin, Confidor Oil (CO)-active ingredient Imidacloprid, Confidor Energy (CE)-active ingredients Deltamethrin and Imidacloprid and Novadim Progress (NP)-active ingredient Dimethoate). The removal efficiency has been assessed by UV-Vis spectroscopy measurements as a function of some parameters, namely polymer dose, grafted chains content and length, pesticides concentration. The P-g-pAPTAC samples showed good removal efficacy at doseop, more than 94% for BM, between 84 and 90% for DC, CO and CE and around 93% for NP. The maximum percentage removal decreased with the pesticides (DC, CO, CE, NP) concentration declining; no effect of BM concentration in suspension on its removal efficiency process has been noted. Differences indicated by zeta potential and particle size distribution measurements regarding the pesticides removal mechanisms by pullulan derivatives (charge neutralization, bridging, etc.) are discussed.

New chromatographic insights on drug:cyclodextrin inclusion complexes and their potential use in drug delivery.

OBJECTIVES: Cyclodextrins (CDs) play a pivotal role in the controlled release of drugs; however, their ability to gradually release drugs is here interrogated: can cyclodextrins, even those that form strong inclusion complexes, sustain a prolonged release of drugs? METHODS: An original chromatographic approach was developed and accordingly we classified and determined drugs that form the most stable inclusion complexes with cyclodextrins. ß-CD and hydroxypropyl-ß-CD (HP-ß-CD) were coupled to pullulan (Pul) microspheres and packed into a chromatographic column. Then, different drugs or model compounds were eluted, and values of the retention time (RT) were determined. In vitro release studies were performed for drugs that form the most stable inclusion complexes. RESULTS: The drugs with the longest RT value form the most stable inclusion complexes with Pul/ß-CD and Pul/HP-ß-CD microspheres. Pul/ß-CD microspheres form more stable inclusion complexes than Pul/HP-ß-CD microspheres. However, in spite of their high stability, they were not able to gradually release the included drug (15 min release time). The cross-chromatographic experiments confirmed the hypothesis that in aqueous solution, drug/cyclodextrin complexes are continuously associated and dissociated. CONCLUSIONS: If the dissociation of the guest molecule is very rapid, why is it expected that these complexes gradually release the drug?

Temperature/pH-Sensitive Double Cross-Linked Hydrogels as Platform for Controlled Delivery of Metoclopramide.

Novel double cross-linked (DC) hydrogels with pH-/temperature-sensitive properties were designed and developed. Therefore, linear pH-sensitive poly(methyl vinyl ether-alt-maleic acid) (P(VME/MA)) macromolecules were absorbed within a thermosensitive poly(N-isopropylacrylamide-co-hydroxyethylacrylamide)-hydrogel (PNH) and, subsequently, cross-linked together through a solvent-free thermal method. As a novelty, double cross-linked hydrogels were obtained from previously purified polymers in the absence of any solvent or cross-linking agent, which are generally harmful for the body. The new DC structures were characterized by FT-IR spectroscopy, SEM, swelling kinetic measurements, and mechanical tests. The resulting scaffolds exhibited interconnected pores and a flexible pattern, compared to the brittle structure of conventional PNH. The swelling kinetics of DC hydrogels were deeply affected by temperature (25 and 37 °C) and pH (7.4 and 1.2). Furthermore, the hydrogels absorbed a great amount of water in a basic environment and displayed improved mechanical properties. Metoclopramide (Met) was loaded within DC hydrogels as a model drug to investigate the ability of the support to control the drug release rate. The results obtained recommended them as convenient platforms for the oral administration of drugs, with the release of the largest part of the active principle occurring in the colon.

Bio-Responsive Carriers for Controlled Delivery of Doxorubicin to Cancer Cells.

The cellular internalization of drug carriers occurs via different endocytic pathways that ultimately involve the endosomes and the lysosomes, organelles where the pH value drops to 6.0 and 5.0, respectively. We aimed to design and characterize pH/temperature-responsive carriers for the effective delivery of the anti-tumoral drug doxorubicin. To this purpose, poly(N-isopropylacrylamide-co-vinylimidazole) was synthesized as an attractive pH/temperature-sensitive copolymer. Microspheres made of this copolymer, loaded with doxorubicin (MS-DXR), disintegrate in monodisperse nanospheres (NS-DXR) under conditions similar to that found in the bloodstream (pH = 7.4, temperature of 36 °C) releasing a small amount of payload. However, in environments that simulate the endosomal and lysosomal conditions, nanospheres solubilize, releasing the entire amount of drug. We followed the NS-DXR internalization using two cancer cell lines, hepatic carcinoma HepG2 cells and lung adenocarcinoma A549 cells. The data showed that NS-DXR are internalized to a greater extent by HepG2 cells than A549 cells, and this correlated with increased cytotoxicity induced by NS-DXR in HepG2 cells compared with A549 cells. Moreover, NS-DXR particles do not cause hemolysis and erythrocytes aggregation. Administered in vivo, NS-DXR localized in the liver and kidneys of mice, and the loading of DXR into NS resulted in the reduced renal clearance of DXR. In conclusion, the newly developed poly(N-isopropylacrylamide-co-vinyl imidazole) particles are biocompatible and may be introduced as carriers for doxorubicin to hepatic tumors.

Eco-Friendly Synthesized PVA/Chitosan/Oxalic Acid Nanocomposite Hydrogels Embedding Silver Nanoparticles as Antibacterial Materials.

PVA/chitosan (PVA/CS) composite hydrogels incorporating silver nanoparticles (AgNPs) were prepared by double-cross-linked procedures: freeze−thawing and electrostatic interactions. Oxalic acid (OA) was used both for solubilization and ionic cross-linking of CS. AgNPs covered by CS (CS-AgNPs) with an average diameter of 9 nm and 18% silver were obtained in the presence of CS, acting as reducing agent and particle stabilizer. The increase of the number of freeze−thaw cycles, as well as of the PVA:CS and OA:CS ratios, resulted in an increase of the gel fraction and elastic modulus. Practically, the elastic modulus of the hydrogels increased from 3.5 kPa in the absence of OA to 11.6 kPa at a 1:1 OA:CS weight ratio, proving that OA was involved in physical cross-linking. The physicochemical properties were not altered by the addition of CS-AgNPs in low concentration; however, concentrations higher than 3% resulted in low gel fraction and elastic modulus. The amount of silver released from the composite hydrogels is very low (<0.4%), showing that AgNPs were well trapped within the polymeric matrix. The composite hydrogels displayed antimicrobial activity against S. aureus, K. pneumoniae or P. gingivalis. The low cytotoxicity and the antibacterial efficacy of hydrogels recommend them for wound and periodontitis treatment.

PVA/Chitosan Thin Films Containing Silver Nanoparticles and Ibuprofen for the Treatment of Periodontal Disease.

Local delivery of drugs or antimicrobial agents is a suitable approach in the management of periodontitis when the infection is localized deep in the pockets and does not adequately respond to mechanical debridement and/or systemic antibiotic treatment. In this context, the objective of this study was to prepare new biocomposite films with antimicrobial, anti-inflammatory, and good mechanical properties to be applied in periodontal pockets. The composite film is eco-friendly synthesized from poly(vinyl alcohol) (PVA) cross-linked with oxidized chitosan (OxCS). Silver nanoparticles (AgNps) were inserted during film synthesis by adding freshly chitosan-capped AgNps colloidal solution to the polymer mixture; the addition of AgNps up to 1.44 wt.% improves the physico-chemical properties of the film. The characterization of the films was performed by FT-IR, atomic mass spectrometry, X-ray spectroscopy, and SEM. The films displayed a high swelling ratio (162%), suitable strength (1.46 MPa), and excellent mucoadhesive properties (0.6 N). Then, ibuprofen (IBF) was incorporated within the best film formulation, and the IBF-loaded PVA/OxCS-Ag films could deliver the drug in a sustained manner up to 72 h. The biocomposite films have good antimicrobial properties against representative pathogens for oral cavities. Moreover, the films are biocompatible, as demonstrated by in vitro tests on HDFa cell lines.

Thermosensitive Poloxamer-graft-Carboxymethyl Pullulan: A Potential Injectable Hydrogel for Drug Delivery.

A thermosensitive copolymer composed of amphiphilic triblock copolymer, poloxamer 407, grafted on hydrophilic pullulan with pendant carboxymethyl groups (CMP) was prepared and characterized. The structure of the new copolymer was assessed by Fourier transform infrared (FT-IR) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The content of the poloxamer in the grafted copolymer was 83.8% (w/w). The effect of the copolymer concentration on the gelation behavior was analyzed by the vertical method and rheological tests; the gel phase of the copolymer occurred at a lower concentration (11%, w/v) as compared with poloxamer (18%, w/v). The starting gelation time under the simulated physiological conditions (phosphate buffer with a pH of 7.4, at 37 °C) was sensitive on the rest temperature before the test, this being 990 s and 280 s after 24 h rest at 4 °C and 20 °C, respectively. The rheological tests evidenced a high elasticity and excellent ability of the copolymer to recover the initial structure after the removal of the applied force or external stimuli. Moreover, the hydrogel has proved a sustained release of amoxicillin (taken as a model drug) over 168 h. Taken together, the results clearly indicate that this copolymer can be used as an injectable hydrogel.

Dual Cross-Linked Chitosan/PVA Hydrogels Containing Silver Nanoparticles with Antimicrobial Properties.

Stable chitosan/PVA-based hydrogels were obtained by combining covalent and physical cross-linking methods. As covalent cross-linkers, epoxy agents with different chain lengths were used, while freeze-thaw cycles were applied for additional physical cross-linking. The chemical structure of the hydrogel was examined by FTIR spectroscopy whereas the morphology was analyzed by SEM, showing well-defined pores with dimensions of around 50 µm in diameter. It was proved that gel fraction and the network morphology were deeply influenced by the synthesis conditions. Chitosan/PVA hydrogel showed a relative high swelling rate, reaching equilibrium in the first hour. The values obtained for the elastic modulus were relatively low (3-30 kPa); as a result, these hydrogels are soft and very flexible, and are ideal candidates for medical applications as wound or oral dressings. In addition, the natural antimicrobial activity of chitosan was enhanced by in situ generation of silver nanoparticles (AgNPs) under UV irradiation. The total amount of Ag from hydrogel was determined by elemental analyses and its crystalline state was confirmed by XRD. The CS/PVA hydrogels entrapped with AgNPs exhibited high inhibitory activity against S. aureus and K. pneumonia. The vitality tests confirmed the lack of cytotoxicity of CS/PVA hydrogels without and with AgNPs.

Alginate/poloxamer hydrogel obtained by thiol-acrylate photopolymerization for the alleviation of the inflammatory response of human keratinocytes.

Hydrogel-based wound dressings have been intensively studied as promising materials for wound healing and care. The mixed-mode thiol-acrylate photopolymerization is used in this paper for alginate/poloxamer hydrogels formation. First, the alginate was modified with thiol groups using the esterification reaction with cysteamine, and second, the terminal hydroxyl groups of poloxamer were esterified with acryloyl chloride to introduce polymerizable acrylate groups. Finally, the cross-linking reaction between the two macromers was performed to produce degradable alginate/poloxamer hydrogels. The optimum conditions for the photo-initiated reaction were studied in order to obtain high gel fractions. The resulting hydrogels have high swelling capacity in simulated physiological conditions, good elasticity and strength, and appropriate porosity, some of the physico-chemical properties required for their applications as wound dressings/patches. The biological assays show that the alginate/poloxamer hydrogels induce proliferation of human keratinocyte and have an anti-inflammatory effect on lipopolysaccharides (LPS)-activated keratinocytes by inhibiting the extracellular signal-regulated kinases (ERK)/ nuclear factor (NF)-kB/ tumor necrosis factor (TNF)-α signalling pathway. Taken together, the results showed that the chemical cross-linked alginate/poloxamer hydrogels may function as a dressing/patch applied directly on the skin lesion to heal the wound by reducing the exacerbated inflammation, the main cause of wound healing delay and local infection.

An intelligent multicompartmental system based on thermo-sensitive starch microspheres for temperature-controlled release of drugs.

An original multicompartmental drug delivery system based on encapsulation of "intelligent" starch microspheres was designed and developed. Starch microspheres with thermo-responsive properties and possessing strong anionic functional groups (-SO(3)H), capable to bind electrostatically drugs, has been prepared. Firstly, the thermo-responsive units based on copolymer of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) with a lower critical solution temperature around 36 degrees C, were grafted on preformed starch microspheres. Secondly, the strong anionic groups (-SO(3)H) were introduced by sequential grafting of 2-acrylamido-2-methyl-1-propanesulfonic acid on the remaining--OH groups of starch. The thermo-sensitive microspheres with sulfonic groups display a sharp phase transition around the human body temperature. They were complexed with the positively-charged metoclopramide (low molecular weight model drug) and then encapsulated in cellulose acetate butyrate microcapsules by an oil-in-water solvent evaporation method. The swelling and diffusion of encapsulated microspheres to the aqueous continuous phase is avoided because the temperature of aqueous phase is higher than volume phase transition temperature (VPTT) of microspheres. This multicompartmental device could develop the background of "smart" implantable drug delivery system for persons that work in dangerous cold places (builders, climbers). When the temperature of the human body decreases below the normal temperature (the threshold temperature could be tuned), the encapsulated microspheres swell extensively in contact with physiological fluids, break the microcapsules and a large amount of bioactive compounds is released, keeping the activity of the vital organs. In normal physiological conditions (above LCST), the microspheres slightly swell, fill up the microcavities of microcapsules, but do not break them and release the drug in microcompartments. These microcompartments become microreservoirs with bioactive compounds and release it with a very low rate maintaining the necessary concentration for a sustained activity of the body.

Smart drug delivery system activated by specific biomolecules.

Essentially, the human body can release in different disease conditions specific biomolecules such as histamines when the body encounters a toxic substance, antibodies which are part of the body's natural immune response or nitric oxide as a cardiovascular signalling molecule. Design and development of "intelligent" delivery systems able to release the therapeutic agent only in the presence of bioactive compounds was presented here. Poly(N-isopropylacrylamide-co-N-(3-aminopropyl)methacrylamide)) (poly(NIPAAm-co-APM)) was synthesized as an exciting pH/temperature sensitive copolymer. Under physiological conditions (pH = 7.4), the APM in copolymer is in the ionized state (pKa = 8.7), highly hydrophilic and therefore the copolymer loses thermosensitive properties. Remarkably, after electrostatic interactions of APM with specific biomolecules, the copolymer restores the thermosensitive property. Thus, the microgels synthesized from this copolymer are in the "inactivated" state at normal physiological pH and temperature (pH = 7.4 and T = 36 °C). In the presence of specific biomolecules, microgels undergo "activation", shrink and expel mechanically a certain amount of drug. It must be mentioned that the pH-sensitive component plays the role of a biosensor, the biomolecule acts as a triggering agent, and the poly(NIPAAm) represents the delivery component (actuator). MTT tests showed that poly(NIPAAm-co-APM) microspheres are completely devoid of toxicity; moreover, the rabbit dermal fibroblasts vastly adhere to the surface of microspheres.

Pullulan derivative with cationic and hydrophobic moieties as an appropriate macromolecule in the synthesis of nanoparticles for drug delivery.

A new amphiphilic pullulan derivative (DBAP-PO) was obtained by grafting tertiary butyl amine and octanoyl groups on the pullulan backbone as cationic and hydrophobic moieties, respectively. The structural characteristics of the modified polymer were investigated by FT-IR and 1H and 13C NMR spectroscopy. The self-association ability in aqueous solution of DBAP-PO was studied by viscosity and fluorescence methods. The intrinsic viscosity of the polymer was determined by Wolf model. The critical aggregation concentration (CAC) value of 0.028 g/dL, determined by fluorescence measurements in the presence of pyrene, was confirmed by capillary viscosimetry and dynamic laser scattering (DLS). Dialysis method was used to demonstrate the capacity of the pullulan derivative to form spherical nanoparticles (d ~ 200 nm) loaded with model drug, sodium diclofenac (DF) (74% entrapment efficiency). The DF release was sustained and pH-dependent. In vitro cytotoxicity as well as morphological studies conducted on the human skin fibroblasts showed that DBAP-PO/DF nanoparticles do not exhibit cytotoxic effects at the pharmacologically relevant concentration of DF, maintaining the typical morphology of the cells.

A new sponge-type hydrogel based on hyaluronic acid and poly(methylvinylether-alt-maleic acid) as a 3D platform for tumor cell growth.

A new sponge-type hydrogel was obtained by cross-linking hyaluronic acid (HA) and poly(methylvinylether-alt-maleic acid) P(MVE-alt-MA) through a solvent-free thermal method. The sponge-type hydrogel was characterized and checked as a support for cell growth. The influence of concentration and weight ratio of polymers on the morphology and hydrogel stability was investigated. The total polymers concentration of 3% (w/w) and the weight ratio of 1:1 were optimal for the synthesis of a stable hydrogel (HA3P50) and to promote cell proliferation. The swelling measurements revealed a high-water absorption capacity of the hydrogel in basic medium. Diphenhydramine (DPH), lidocaine (Lid) and propranolol (Prop) were loaded within the hydrogel as a model drugs to investigate the ability of drug transport and release. In vitro studies revealed that HA3P50 hydrogel promoted the adhesion and proliferation of human hepatocellular carcinoma cell line HepG2, providing a good support for 3D cell culture to obtain surrogate tumor scaffold suitable for preclinical anti-cancer drug screening.