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The current challenges in the food packaging field are, on one side, replacing plastic from non-renewable sources with biopolymers and, on the other hand, generating a packaging material with attractive properties for the consumer. Currently, the consumer is ecologically concerned; the food packaging industry must think ahead to satisfy their needs. In this context, the utilization of polyelectrolyte complexes (PECs) in this industry presents itself as an excellent candidate for fulfilling these requirements. PECs possess enticing characteristics such as encapsulation, protection, and transportation, among others. On the other hand, diverse types of biopolymers have been used in the formation of PECs, such as alginate, cellulose, gelatin, collagen, and so on. Hence, this paper reviews the use of PECs in food packaging where chitosan forms polyelectrolyte complexes.
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Quitosana , Polieletrólitos , Embalagem de Alimentos , Biopolímeros , CeluloseRESUMO
The development of biobased antioxidant active packaging has been valued by the food industry for complying with environmental and food waste concerns. In this work, physicochemical properties for chitosan composite films as a potential active food packaging were investigated. Chitosan films were prepared by solution casting, plasticized with a 1:2 choline chloride: glycerol mixture as a deep eutectic solvent (DES) and incorporated with 0-10% of optimized açaí oil polyelectrolyte complexes (PECs). Scanning electron microscopy and confocal laser scanning microscopy revealed that the chitosan composite films were continuous and contained well-dispersed PECs. The increased PECs content had significant influence on the thickness, water vapor permeability, crystallinity (CrD) and mechanical and dynamic behavior of the films, as well as their antioxidant properties. The tensile strength was reduced in the following order: 11.0 MPa (control film) > 0.74 MPa (5% DES) > 0.63 MPa (5% DES and 5% PECs). Films containing 2% of PECs had an increased CrD, ~6%, and the highest elongation at break, ~104%. Films with 1% of PECs displayed the highest antioxidant properties against the ABTS and DPPH radicals, ~6 and ~17 mg TE g-1, respectively, and highest equivalent polyphenols content (>0.5 mg GAE g-1). Films with 2% of particles were not significantly different. These results suggested that the chitosan films that incorporated 1-2% of microparticles had the best combined mechanical and antioxidant properties as a potential material for food packaging.
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Quitosana , Eliminação de Resíduos , Antioxidantes/química , Quitosana/química , Embalagem de Alimentos/métodos , Solventes Eutéticos Profundos , Cápsulas , Alimentos , PermeabilidadeRESUMO
The complexation between two oppositely charged polyelectrolytes (PE) can lead liquid-liquid (complex coacervates, CC) or liquid-solid (solid precipitates, SP) phase separations. Herein, the effect of pH (2-11) and ionic strength (I, 0.05-1.0 M KCl) on the associative interactions between chitosan (QL)-alginate (SA) and QL-Pectin (Pec), polysaccharides widely used in biotechnology field, is described. pH and I, exhibited significant effect on the structure and phase transitions by modifying the ionization degree (α), pka, and associative interactions between PE. Onset of binding was established at pHc 9, while continued acidification (pHτ 5.8) led to simultaneous CC and SP exhibiting a maximum turbidity in both systems. At pHδ 4.0, QL-Pec showed preferably CC structures whereas QL-SA maintained the CC and SP structures. At pHω 2, the associative interactions were suppressed due to the low ionization of Pec and SA. I (1.0 M) significantly diminished the interactions in QL-Pec due to charge screening. Molecular weight, second virial coefficient, hydrodynamic size, ionizable groups, and persistence length of polyion, influenced on the phase behavior of QL-Pec and QL-SA systems. Therefore, CC and SP are found simultaneously in both systems, their transitions can be modulated by intrinsic and environmental conditions, expanding the functional properties of complexed polysaccharides.
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Quitosana , Quitosana/química , Alginatos/química , Pectinas , Concentração de Íons de Hidrogênio , Polieletrólitos/química , PolissacarídeosRESUMO
In this work, we report the phase behavior of polyelectrolyte complex coacervates (PECs) of poly(acrylate) (PA-) and poly(diallyldimethylammonium) (PDADMA+) in the presence of inorganic salts. Titrations of the polyelectrolytes in their acidic and alkaline forms were performed to obtain the coacervates in the absence of their small counterions. This approach was previously applied to the preparation of polymer-surfactant complexes, and we demonstrate that it also succeeded in producing complexes free of small counterions with a low extent of Hofmann elimination. For phase behavior studies, two different molar masses of poly(acrylate) and two different salts were employed over a wide concentration range. It was possible to define the regions at which associative and segregative phase separation take place. The latter one was exploited in more details because the segregation phenomenon in mixtures of oppositely charged polyelectrolytes is scarcely reported. Phase composition analyses showed that there is a strong segregation for both PA- and PDADMA+, who are accompanied by their small counterions. These results demonstrate that the occurrence of poly-ion segregation in these mixtures depends on the anion involved: in this case, it was observed with NaCl, but not with Na2SO4.
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Nanostructured polyelectrolyte complexes (nano PECs) were obtained by polyelectrolyte complexation technique from chitosan (CS) and sodium alginate (SA). Different polymer proportions were tested, as well as the addition order and homogenization type, to assess the influence on the nano PECs characteristics. The spherical shape and nanometric scale of the systems were observed by scanning electron microscopy (SEM). Nano PECs size, PDI, and zeta potential (ZP) ranged from 252 to 616 nm, from 0.22 to 0.73 and -50 to 30 mV, respectively. The increase of polymer proportion and the ultra-turrax homogenization led to the enlargement of particles size and PDI. However, no influence was observed on the ZP. The NP1s-Rb and NP4s-Rb, obtained through the sonicator with rifampicin (RIF) added before the CS and SA complexation, were selected due to the most promising characteristics of diameter (301 and 402 nm), PDI (0.27 and 0.26), and RIF incorporation (78 and 69%). The release profiles of RIF incorporated in both nano PECs were similar, with a sustained release of the drug for 180 min in phosphate buffer pH 7.2. The Weibull and the Korsmeyer-Peppas models better describe the RIF release from NP1s-Rb and NP4s-Rb, respectively, demonstrating that the release process was driven by different mechanism according to the particle composition. The nano PECs were lyophilized to prolong it stability and for possible nebulization. The addition of dextrose to the system allowed for resuspension after lyophilization. Therefore, with the results obtained, the incorporation of RIF in nano PECs based on CS and SA presents a promising system for the treatment of tuberculosis.
Assuntos
Quitosana , Tuberculose , Alginatos/química , Quitosana/química , Portadores de Fármacos/química , Humanos , Polieletrólitos/química , Polímeros , RifampinaRESUMO
Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (21 × 21 × 31), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811-1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553-739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity.
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In the present study, supramolecular polyelectrolyte complexes (SPEC) based on a cyclodextrin-grafted chitosan derivative and carrageenan were prepared and evaluated for controlled drug release. Samples were characterized by FTIR, SEM, and ζ-potential measurements, which confirmed the formation of the polymeric complex. The phenolphthalein test confirmed the presence and availability of inclusion sites from the attached ßCD. Silver sulfadiazine was used as the model drug and the association with the SPEC was studied by FTIR and computational molecular modeling, using a semi-empirical method. DRS and TEM analyses have shown that Ag+ ions from the drug were reduced to form metallic silver nanostructures. In vitro tests have shown a clear bacterial activity toward Gram-positive bacteria Staphylococcus aureus and Enterococcus durans/hirae and Gram-negative bacteria Klebsiella pneumoniae and Escherichia coli. Finally, this work shows that ßCD-chitosan/carrageenan supramolecular polyelectrolyte complexes hold an expressive potential to be applied as a polymer-based system for controlled drug release.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Carragenina/química , Quitosana/química , Ciclodextrinas/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Polieletrólitos/química , Polieletrólitos/farmacologia , Biologia Computacional/métodos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Íons/química , Testes de Sensibilidade Microbiana , Nanoestruturas/química , Prata/química , Sulfadiazina de Prata/química , Sulfadiazina de Prata/farmacologiaRESUMO
Conventional strategies (Turkevich's, and modified Turkevich's methods) often synthesize gold nanoparticles (AuNPs). These pathways produce AuNPs using toxic chemistries to reduce Au(III) and stabilize Au(0) atoms upon the AuNP surfaces. To overcome the disadvantages of conventional approaches, chitosan and chitosan-based materials associate with Au(III) to produce composites. Chitosan and derivatives reduce Au(III) and stabilize AuNPs, promoting biocompatibility to the composites, following approaches in-situ. In this review, we report methods to develop chitosan/AuNPs-based composites. The main criticism is about the mechanism of composite formation. Also, we highlight applications of chitosan/AuNPs-based devices in the biomedical arena. We report the synthesis of biosensors, drug delivery devices, scaffolds, antimicrobial coatings, and others. The major criticism is concerning the material design and the lack of data regarding the composite biocompatibility. We support a critical viewpoint.
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Materiais Biocompatíveis/química , Quitosana/química , Ouro/química , Nanopartículas Metálicas/química , Animais , Pesquisa Biomédica/métodos , HumanosRESUMO
Studies report the production of gold nanoparticles (AuNPs) and polysaccharides-based composites. However, there are few reports about AuNPs synthesis in-situ followed by the formation of hydrogel composites. Here, we show AuNPs synthesis in-situ into the pectin solutions to yield cytocompatible pectin-capped AuNPs/chitosan hydrogel composites. Visible spectroscopy and dynamic light scattering measurements confirm the AuNPs synthesis. The hydrodynamic radius of the pectin-capped AuNPs ranges from approximately 510 to 721 nm, while the Zeta potential is around -43 mV. Scanning electron microscopy shows that the composites present compact structures. Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy characterize the composites as well. Hydrogels (with or without AuNPs) containing the highest pectin content (at 4.12 pectin/chitosan weight ratio) have low stability (disintegrates approximately 60% after 14 days in phosphate buffer). Composites obtained at 3.75 pectin/chitosan weight ratio disintegrate between 25 and 30% after 14 days in phosphate buffer (physiological condition = pH 7.4). The AuNPs reinforce the hydrogel structures, increasing the elastic modulus (from 3.5 to 7.6 Pa) and decreasing the water uptake from 4465 to 2976%. 3.75 PT/CS weight ratio and 3.0 × 10-4 M Au(III) content provide a durable, cytocompatible, and superabsorbent hydrogel composite. These properties can support materials for drug delivery purposes.
Assuntos
Absorção Fisico-Química , Quitosana/química , Ouro/química , Hidrogéis/química , Nanopartículas Metálicas/química , Pectinas/química , Tecido Adiposo/citologia , Animais , Morte Celular , Sobrevivência Celular , Espectroscopia Fotoeletrônica , Polieletrólitos/química , Espectrofotometria Ultravioleta , Células-Tronco/citologiaRESUMO
Platelet-rich plasma (PRP) associated with high molecular weight hyaluronic acid (HA) has been clinically used for tissue regeneration in orthopedics. Despite the recognized beneficial clinical outcomes (e.g., early pain control, improvement of patients' functional limitation and longer-term effectiveness compared to PRP and HA alone in mild and moderate osteoarthritis treatments), its use is still challenging and controversial due to lack of standardization of association practical protocols. Moreover, most studies neglect the matrix structure, that generates the ultimate properties of the association among platelets, fibrin network and the microparticles. In the present work, we aimed to analyze the influence of the PRP/HA association with a controlled matrix structure on the stability, rheological behavior, release of growth factors and in vitro proliferation of human adipose-derived mesenchymal cells (h-AdMSCs). The attenuation of the negative charge of HA was also evaluated. Pure PRP (P-PRP) (i.e., plasma enriched with platelets and poor in leukocytes) was prepared by centrifugation and activated with serum and calcium chloride (AP-PRP). Autocrosslinked hyaluronic acid (AHA) was prepared by organocatalyzed auto-esterification and structured in microparticles (MPAHA) by shearing. The attenuation of the negative charge of MPAHA was performed with chitosan (CHT) by polyelectrolyte complexation yielding MPAHA-CHT. The results showed that microparticles (MPs) have viscoelastic properties, extrusion force and swelling ratio appropriate for injectable applications. The association of AP-PRP with the controlled structure of MPAHA and MPAHA-CHT formed a matrix composed of platelets and of a fibrin network with fibers around 160 nm located preferably on the surface of the MPs with an average diameter of 250 µm. Moreover, AP-PRP/MPAHA and AP-PRP/MPAHA-CHT associations were non-toxic and supported controlled growth factor (PDGF-AB and TGF-ß1) release and in vitro proliferation of h-AdMSC with a similar pattern to that of AP-PRP alone. The best h-AdMSC proliferation was obtained with the AP-PRP/MPAHA-CHT75:25 indicating that the charge attenuation improved the cell proliferation. Thus, the association of AP-PRP with the controlled structure of HA can be a valuable approach for orthopedic applications.
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Here we report a new and straightforward method to yield durable polyelectrolyte complexes (hydrogel PECs) from gellan gum (GG) and chitosan (CS) assemblies, without metallic and covalent crosslinking agents, commonly used to produce GG and CS-based hydrogels, respectively. This new approach overcomes challenges of obtaining stable and durable GG-based hydrogels with structural homogeneity, avoiding precipitation and aqueous instability, typical of PEC-based materials. PECs are created by blending CS:GG solutions (at 60⯰C) with GG:CS weight ratios between 80:20 to 40:60. X-ray photoelectron spectroscopy (XPS) analysis shows that CS-GG chains are interacting by electrostatic and intermolecular forces, conferring a high degree of association to the washed PECs, characteristic of self-assembling of polymer chains. The CS:GG weight ratio can be tuned to improve polyelectrolyte complex (PEC) high porosity, stability, porous homogeneity, and degradation rate. Physical and thermosensitive CS/GG-based hydrogels can have advantages over conventional materials produced by chemical processes.
Assuntos
Quitosana/química , Polissacarídeos Bacterianos/química , Materiais Biocompatíveis/química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Estrutura Molecular , Análise Espectral , TermodinâmicaRESUMO
Alginate-based polyelectrolyte complexes (PECs) and hydrogel were engineered as platforms for local bevacizumab (BVZ) therapy. This study provides deep comprehension on the microstructures of such systems, and their correlation with drug-release patterns. PECs and hydrogel were characterized using Fourier transform infrared spectroscopy, small-angle X-ray scattering, scanning electron microscopy, atomic force microscopy, and porosimetry. Structural investigations indicated that PECs are formed by supramolecular interactions, resulting in physically cross-linked polymer networks, whereas the BVZ-loaded hydrogel has a more compact and rigid structure, promoting better entrapment of BVZ. PECs and hydrogel were able to control the BVZ release for 4 and 8 days, respectively. Their release profiles correlated best with the Higuchi and Korsmeyer-Peppas models, respectively, indicating drug diffusion as the limiting step for drug release. Furthermore, BVZ remained biologically active in vitro after its incorporation into the hydrogel system. Together, these studies confirm that PECs and hydrogel exhibit different porous structures and physicochemical properties, making them promising platforms that allow the modulation of BVZ release meeting different requirements.
Assuntos
Alginatos/química , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Portadores de Fármacos/química , Inibidores da Angiogênese/farmacocinética , Bevacizumab/farmacocinética , Liberação Controlada de Fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/química , Concentração de Íons de Hidrogênio , Polieletrólitos/química , Porosidade , Proteínas Recombinantes/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Processing stable polysaccharide membranes with suitable mechanical properties has been challenging for applications in wound healing and tissue engineering. Here we expand the characterization of pectin/chitosan (PT/CS) membranes (without covalent crosslinking), which we recently reported. Membranes containing pectin (PT) excess were formed, and PT/CS ratio can be tuned to enhance the mechanical strength, and to modulate hydrophilicity and cytocompatibility. The surface wettability and swelling properties of the polyelectrolyte complexes (PECs) played an important role to promote the attachment of stem cells. These PECs membranes have ultimate tensile strength similar to that of human skin, which is on the order of ten times higher than similar previously reported polysaccharide materials. We show for the first time that these new PT/CS membranes may promote anchorage, adhesion and support human stem cell growth, making them candidate materials for tissue engineering purposes.
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Quitosana/farmacologia , Pectinas/farmacologia , Células-Tronco/citologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quitosana/química , Humanos , Tamanho da Partícula , Pectinas/química , Espectroscopia Fotoeletrônica , Estresse Mecânico , Propriedades de Superfície , Engenharia Tecidual , MolhabilidadeRESUMO
Processing water-soluble polysaccharides, like pectin (PT), into materials with desirable stability and mechanical properties has been challenging. Here we report a new method to create water stable and mechanical resistant polyelectrolyte complex (PEC) membranes from PT and chitosan (CS) assemblies, without covalent crosslinking. This new method overcomes challenges of obtaining stable and durable complexes, by performing the complexation at low pH, enabling complex formation even when using an excess of PT, and when using PT with high degree of O-methoxylation. By performing the complexation at low pH, the complexes form with a high degree of intermolecular association, instead of forming by electrostatic complexation. This method avoids precipitation, and overcomes the aqueous instability typical of PT/CS complexes. After neutralization, the PEC membranes display features characteristic of a high degree of intermolecular association because of the self-assembling of polymer chains. The PT/CS ratio can be tuned to enhance the mechanical strength (σâ¯=â¯39â¯MPa) of the membranes. These polysaccharide-based materials can demonstrate advantages over synthetic materials for technological applications.
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This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, tmax, area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.
Assuntos
Antibacterianos , Ciprofloxacina , Polieletrólitos , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/urina , Ciprofloxacina/administração & dosagem , Ciprofloxacina/química , Ciprofloxacina/farmacocinética , Ciprofloxacina/urina , Estudos Cross-Over , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Método Duplo-Cego , Liberação Controlada de Fármacos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Polieletrólitos/administração & dosagem , Polieletrólitos/química , Polieletrólitos/farmacocinética , Comprimidos , Adulto JovemRESUMO
This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200 µm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.
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Alginatos/química , Cloreto de Cálcio/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Polieletrólitos/química , Polímeros/química , Administração Intravaginal , Alginatos/administração & dosagem , Química Farmacêutica , Difusão , Liberação Controlada de Fármacos , Ácido Glucurônico/administração & dosagem , Ácido Glucurônico/química , Ácidos Hexurônicos/administração & dosagem , Ácidos Hexurônicos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/administração & dosagem , Concentração de Íons de HidrogênioRESUMO
Cardiovascular disease is the largest single cause of morbid-mortality in the world. However, there is still no pharmaceutical treatment that directly targets the blood vessel wall instead of just controlling the risk factors. Here, we produced polyelectrolyte complexes (PECs) by a simple and reproducible polyelectrolyte complexation method between low molecular mass dermatan sulfate (polyanionic polysaccharide) and chitosan (polycationic polysaccharide), and evaluated the cellular uptake by vascular endothelial cells. The composition and the composition homogeneity of PECs were confirmed by (13)C-CP-MAS spectroscopy and by polyacrylamide gel electrophoresis, respectively. The hydrodynamic radius, determined by dynamic light scattering, was 729±11nm. PECs were not cytotoxic for a murine heart endothelium-derived cell line. Fluorescent confocal microscopy showed the specific uptake of fluorescently-labeled PECs by endothelial cells when they were cultured alone or in the presence of macrophages. Overall, these findings confirmed the potential of these PECs for targeting different agents to the vessel wall in the prevention, diagnosis, and therapy of vascular disease.
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Quitosana/química , Dermatan Sulfato/química , Polieletrólitos/química , Doenças Vasculares/diagnóstico , Doenças Vasculares/tratamento farmacológico , Animais , Transporte Biológico , Células Endoteliais/metabolismo , Camundongos , Peso Molecular , Polieletrólitos/metabolismo , Polieletrólitos/uso terapêutico , Células RAW 264.7 , Doenças Vasculares/prevenção & controleRESUMO
For the first time, polyelectrolyte complex based on poly[(2-dimethylamino) ethyl methacrylate] (PDMAEMA) and chondroitin sulfate (CS) was prepared. The properties of novel material and precursors were investigated by WAXS, FTIR, TGA, SEM and DLS analysis. The PDMAEMA/CS PECs presented hydrophilic-hydrophobic transition at pHs 6.0, 7.0 and 8.0 whereas the non-complexed PDMAEMA showed such a transition at pH 8.0 and not at pHs 6.0 and 7.0. Studies of CS release from PECs at pHs 6 and 8 confirmed that the samples possess the potential to release the CS in alkaline and not in acidic conditions. Since PECs are thermo-responsive due to the reduction of LCST caused by the increase in pH, the release of CS was dependent on temperature and pH factors. Cytotoxicity assays using healthy VERO cells showed that the complexation between CS and PDMAEMA increased the PECs' biocompatibility related to PDMAEMA. However, the biocompatibility depends on the amount of CS present in the PECs.
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Sulfatos de Condroitina/química , Composição de Medicamentos , Metacrilatos/química , Nylons/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Sulfatos de Condroitina/toxicidade , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Eletrólitos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Metacrilatos/toxicidade , Nylons/toxicidade , Solubilidade , Propriedades de Superfície , Temperatura , Células VeroRESUMO
With the aim to provide more rational basis about the potentiality of hyaluronic acid (or hyaluronan) as drug carrier a set of ionic complexes of its acid form (HA) and its sodium salt (NaHA) with three model drugs (D) (atenolol, propranolol and lidocaine) were prepared. Besides NaHA subjected to hyalurodinase depolimerization (NaHA(d)) was also used. Transparent dispersions were obtained. They exhibited negative electrokinetic potential and a high degree of counterionic condensation with affinity constants (log Kcc) in the range of 5.8-6.1 for propranolol complexes (pK(a) 9.45) and 4.0-4.6 for lidocaine ones (pK(a) 7.92). Delivery rates of D from the complexes were measured in a Franz-type bicompartimental device. Loaded D were slowly released from the three types of complexes, even when a neutral salt was added to the dispersion placed in the donor compartment, revealing the high affinity between the protonated drugs and the ionisable groups of the polymer. Complex dispersions based on HA or on NaHA(d) exhibited lower viscosity than those of NaHA but their complexing ability remained unaltered. The results reported on equilibrium and release properties of Hyaluronan-model D complexes contribute to expand the use of HA and NaHA as drug carriers for different routes of administration.