Biopolymer Carriers Research Articles

Creation and analysis of hybrid nanocomposites based on dioxidine and nanoparticles of bioactive metals embedded in cryostructurated gelatin matrices

This paper is devoted to the creation of hybrid nanocomposites based on the antibacterial drug dioxidine and bioactive metals - silver and copper. The obtained materials were analyzed using the methods of NMR, UV and IR spectroscopy, low-temperature adsorption of argon, SEM and TEM. It is shown that they are silver nanoparticles with a size of 2-30 nm or copper nanoparticles with a size of 10-40 nm, incorporated into dioxidine particles with a size of 50-350 nm. The obtained drug nanocomposites were embedded into wide-porous biopolymer cryostructurated gelatin-based matrices. The possibility of the release of drug components from a biopolymer carrier and manifestation of its antibacterial activity has been shown. At the same time, hybrid nanocomposites based on metals and antibacterial drugs showed increased activity to suppress the growth of microbial cells of Escherichia coli 52, Staphylococcus aureus 144, Mycobacterium cyaneum 98, then their components separately.

Synthesis and anti-metastasis activities of norcantharidin-conjugated carboxymethyl chitosan as a novel drug delivery system

Carboxymethyl chitosan (CMCS), a water-soluble derivative of chitosan possessing numerous enhanced physicochemical and biological properties, has emerged as a promising biopolymer carrier for new drug delivery. Norcantharidin (NCTD) is an effective anti-tumor compound with severe nephrotoxicity. In this study, norcantharidin-conjugated carboxymethyl chitosan (CMCS-NCTD) was synthesized to reduce systemic toxicity and improve anti-tumor efficiency of NCTD. Our results demonstrated that CMCS-NCTD could significantly inhibit migration of tumor cells both in vitro and in vivo in a dose-dependent manner (P < 0.05). The enhanced anti-tumor effects of CMCS-NCTD were confirmed by inhibiting the growth of solid tumors and extending survival time of tumor-bearing mice. Further investigation for the underlying mechanisms indicated that CMCS-NCTD could inhibit tumor angiogenesis and reduce degradation of extracellular matrix by regulating the expressions of VEGF, MMP-9 and TIMP-1. Overall, our findings suggested that CMCS-NCTD was an excellent polymer derivative for cancer treatment, and CMCS was a promising platform for efficient delivery of anti-cancer drugs.

Novel Biodegradable Polymeric Microparticles Facilitate Scarless Wound Healing by Promoting Re-epithelialization and Inhibiting Fibrosis.

Despite decades of research, the goal of achieving scarless wound healing remains elusive. One of the approaches, treatment with polymeric microcarriers, was shown to promote tissue regeneration in various in vitro models of wound healing. The in vivo effects of such an approach are attributed to transferred cells with polymeric microparticles functioning merely as inert scaffolds. We aimed to establish a bioactive biopolymer carrier that would promote would healing and inhibit scar formation in the murine model of deep skin wounds. Here we characterize two candidate types of microparticles based on fibroin/gelatin or spidroin and show that both types increase re-epithelialization rate and inhibit scar formation during skin wound healing. Interestingly, the effects of these microparticles on inflammatory gene expression and cytokine production by macrophages, fibroblasts, and keratinocytes are distinct. Both types of microparticles, as well as their soluble derivatives, fibroin and spidroin, significantly reduced the expression of profibrotic factors Fgf2 and Ctgf in mouse embryonic fibroblasts. However, only fibroin/gelatin microparticles induced transient inflammatory gene expression and cytokine production leading to an influx of inflammatory Ly6C+ myeloid cells to the injection site. The ability of microparticle carriers of equal proregenerative potential to induce inflammatory response may allow their subsequent adaptation to treatment of wounds with different bioburden and fibrotic content.

Polysaccharide Nanoparticles for Targeted Cancer Therapies.

Despite extensive advances have been made in constructing polysaccharide-based nanomedicines for target cancer therapy due to their biocompatibility, easy-functionalizability and high targeting property, there is no review concentrating the significance of the intrinsic targeting properties of polysaccharides. This review mainly focuses on the recent progress on polysaccharide-based nanoparticles which have been applied in gene delivery, drug delivery and theranostics for targeted cancer therapies. Notably, representative polysaccharides with intrinsic targeting capability used as targeting ligand are well discussed. It has been found that polysaccharides have become a class of promising biopolymer carrier materials to deliver anti-cancer therapeutic molecules. Among all of polysaccharides, those who are with intrinsic properties of targeting are most frequently used. Therefore, this review revealed the importance of understanding the natural functions of polysaccharides to tailor nanocarrier platforms and ultimately surmount challenges in targeted cancer therapy.

Biopolymer strategy for the treatment of Wilson's disease

Wilson's disease is a genetic disorder that causes excessive accumulation of copper in the body, leading to toxic damage, especially in the liver and nervous system. The current treatment cause burdensome side effects. We describe the use of chemically modified biopolymer carriers based on microcrystalline cellulose and chitosan containing the highly specific copper chelator 8-hydroxyquinoline as a new type of therapy for Wilson's disease. The chelators can scavenges copper ions released from food during digestion and copper ions present in secretions in the gastrointestinal tract. Because the chelator is covalently bound to indigestible biopolymer carriers (crosslinked chitosan or modified cellulose), it is not taken up by the gastrointestinal tract and it can be eliminated through the feces, avoiding unwanted side effects. This concept was tested on Wistar rats, which received a radioactive 64CuCl2 solution together with the polymers with covalently bound 8-hydroxyquinoline through a gastric probe. 64Copper complex uptake from the gastrointestinal tract was significantly inhibited by both chelating polymers. With the modified polymers, the presence of 64Cu was detected mostly in the gastrointestinal tract, not in the internal organs. These findings indicate modified cellulose and crosslinked chitosan, with covalently bound 8-hydroxyquinoline exhibited the potential to be excellent therapeutics for treating Wilson's disease.

A Maternally Sequestered, Biopolymer-Stabilized Vascular Endothelial Growth Factor (VEGF) Chimera for Treatment of Preeclampsia.

BackgroundPreeclampsia is a hypertensive syndrome that complicates 3% to 5% of pregnancies in the United States. Preeclampsia originates from an improperly vascularized and ischemic placenta that releases factors that drive systemic pathophysiology. One of these factors, soluble fms‐like tyrosine kinase‐1, is believed to sequester vascular endothelial growth factor (VEGF), leading to systemic endothelial dysfunction and hypertension. With the goal of targeting soluble fms‐like tyrosine kinase‐1 while simultaneously preventing fetal exposure to VEGF, we fused VEGF to elastin‐like polypeptide, a biopolymer carrier that does not cross the placental barrier (ELP‐VEGF).Methods and Results ELP‐VEGF restored in vitro endothelial cell tube formation in the presence of plasma from placental ischemic rats. Long‐term administered ELP‐VEGF in pregnant rats accumulated in maternal kidneys, aorta, liver, and placenta, but the protein was undetectable in the pups when administered at therapeutic doses in dams. Long‐term administration of ELP‐VEGF in a placental ischemia rat model achieved dose‐dependent attenuation of hypertension, with blood pressure equal to sham controls at a dose of 5 mg/kg per day. ELP‐VEGF infusion increased total plasma soluble fms‐like tyrosine kinase‐1 levels but dramatically reduced free plasma soluble fms‐like tyrosine kinase‐1 and induced urinary excretion of nitrate/nitrite, indicating enhanced renal nitric oxide signaling. ELP‐VEGF at up to 5 mg/kg per day had no deleterious effect on maternal or fetal body weight. However, dose‐dependent adverse events were observed, including ascites production and neovascular tissue encapsulation around the minipump.Conclusions ELP‐VEGF has the potential to treat the preeclampsia maternal syndrome, but careful dosing and optimization of the delivery route are necessary.

Development of amphoteric alginate/aminated chitosan coated microbeads for oral protein delivery

A new amphoteric biopolymer carrier based on alginate and aminated chitosan coated microbeads (Alg/AmCS) was developed and characterized for bovine serum albumin (BSA) protein delivery. The amphoteric character was investigated through studying the swelling and in vitro BSA release behaviors of the developed microbeads in simulated gastric (SGF; pH1.2), intestinal (SIF; pH6.8), and colonic (SCF; pH7.4) fluids. The pH sensitivity was found to depend on the amount of AmCS in the coating medium. The results were interpreted from the view of the individual pH sensitivity of alginate and aminated chitosan in addition to the ionic interaction between them under the studied pHs. Besides; it was found that the BSA loading efficiency (LE) exceeded 82% regardless of the initial concentration of BSA. The released amount of BSA reached approximately 63% and 86% in SIF and SCF, respectively, using 0.25% AmCS. The stability of alginate microbeads in SCF was improved with increasing AmCS concentration in the coating medium up to 2%. Furthermore, the developed microbeads demonstrated their ability for biodegradation in addition to their antibacterial activities against selected bacterial strains. The results clearly suggested that Alg/AmCS coated microbeads could be suitable carriers for site-specific protein delivery in the intestinal and colon tracts.

Hyaluronic acid concentration-mediated changes in structure and function of porous carriers for corneal endothelial cell sheet delivery

In this study, the effects of hyaluronic acid (HA) concentrations (0.05–1.25wt.%) on the properties of porous carriers for corneal endothelial tissue engineering were investigated. The pore size and porosity gradually increased with decreasing solid content. However, at relatively low HA concentration (i.e., 0.05wt.%), the material samples contained small interior pores and a dense surface skin layer, probably due to no gas bubble effect on the stirring processing of porous microstructures of freeze-dried polysaccharide hydrogels. The carriers prepared from 0.25wt.% HA solution had the highest freezable water content and oxygen and glucose permeability among the samples evaluated. Results of cell viability assays and quantitative real-time reverse transcription polymerase chain reaction analyses showed that the HA concentration-related alteration of porous microstructure dictates the compatibility of biopolymer carriers with corneal endothelial cell (CEC) cultures. In vivo studies demonstrated that the CEC sheet/HA carrier construct implants are therapeutically efficacious in the reconstruction of endothelial scrape-wounded corneas. It is concluded that the polysaccharide concentration is the major factor for affecting the processing of carriers and their structure and function. Porous hydrogels prepared from 0.25wt.% HA solution are capable of delivering bioengineered CEC sheets to the posterior surface of cornea.

Influence of Chitosan Coating on Mechanical Stability of Biopolymer Carriers with Probiotic Starter Culture in Fermented Whey Beverages

The aim of this study was to improve the mechanical stability of biopolymer carriers and cell viability with addition of chitosan coating during fermentation process and product storage. Dairy starter culture (1% (w/v)) was diluted in whey and mixed with sodium alginate solution and the beads were made using extrusion technique. The mechanical stability of coated and uncoated beads, the release behavior, and the viability of encapsulated probiotic dairy starter culture in fermented whey beverages were analyzed. The mechanical properties of the beads were determined according to force-displacement and engineering stress-strain curves obtained after compression testing. It was observed that addition of chitosan as a coating on the beads as well as the fermentation process increased the elastic modulus of the calcium alginate-whey beads and cell survival. The current study revealed that the coating did not significantly improve the viability of probiotics during the fermentation but had an important influence on preservation of the strength of the carrier during storage. Our results indicate that whey-based substrate has positive effect on the mechanical stability of biopolymer beads with encapsulated probiotics.

Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation

Solid dispersion systems of telmisartan (a poorly water-soluble antihypertension drug) with biopolymer carrier chitosan have been investigated in this study. The mechanism of solubilization of chitosan for drug has been studied. In addition, the influence of several factors was carefully examined, including the preparation methods, the drug/carrier weight ratios, and the milling time. Drug dissolution and physical characterization of different binary systems were studied by in vitro dissolution test, particle size distribution, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscopy. The results presented that the weak basic property of chitosan appeared as the main driving force for the drug dissolution enhancement. Other effects such as decreased drug crystallinity and size played a positive contributory role. Among the preparation methods, cogrinding was the best method showing strong drug amorphization, reduced particle size, and enhanced dissolution. The drug dissolution markedly improved with increasing the amount of chitosan in solid mixtures. As a result, a significant effect of chitosan increasing telmisartan dissolution has been demonstrated, and cogrinding in a roll ball mill was the best way to prepare solid dispersions, which had high degree of uniformity in drug content and had a practical application in manufacturing.

Proekologiczne dyspersyjne modyfikacje powierzchni materialow celulozowych Cz. I. OTRZYMYWANIE I WLASCIWOSCI POWLOKOTWORCZYCH WODNYCH DYSPERSJI WOSKU CANDELILLA

Aqueous dispersions (25 %) of natural hydrophobic Candelilla wax has been prepared with various emulsifiers: low molecular (non-ionic and anionic) and macromolecular (protein and polysaccharide). The dispersions were obtained using ultrasonic homogenization, and the resulting emulsions were applied for the modification of porous „inner” side of cellulosic material (paperboard). By mixing the emulsions with biopolymer carrier (starch sodium octenyl succinate — OSA), film-forming compositions were obtained, having an appropriate viscosity to form high-quality coatings. More homogeneous emulsions were prepared using soy protein and anionic emulsifier, while the systems with non-ionic emulsifier Tween 20 showed the best barrier properties. Particle size measurements indicated that the most favourable conditions for obtaining Candelilla emulsions were: temperature of 90 °C and sonication time of 5 minutes. The most stable dispersion was obtained using 25 % Candelilla wax/water emulsion containing 4 % emulsifier Tween 20.

Complex coacervation of pea protein isolate and alginate polysaccharides

Complex coacervation between pea protein isolate (PPI) and alginate (AL) was investigated as a function of pH (1.50–7.00) and mixing ratio (1:1–20:1 PPI:AL) by turbidimetric analysis and electrophoretic mobility during an acid titration. Conformational changes to the secondary structures during coacervation were also studied by Raman spectroscopy. Critical structure-forming events associated with the formation of soluble (pH 5.00) and insoluble (pH 2.98) complexes were found for a 1:1 PPI–AL mixture, with optimal biopolymer interactions occurring at pH 2.10 (pHopt). As mixing ratios increased between 4:1 and 8:1, critical pHs shifted towards higher pH. Maximum coacervate formation at pHopt occurred at a mixing ratio of 4:1. Electrophoretic mobility measurements showed a shift in net neutrality from pH 4.00 in homogenous PPI solutions, to pH 1.55 for the 1:1 mixture. As biopolymer ratios increased towards 8:1 PPI:AL, net neutrality shifted to higher pHs (∼3.80). Raman spectroscopy revealed minimal complexation-induced conformational changes. Findings could aid in the design of pH-sensitive biopolymer carriers for use in functional food and bio-material applications.

Fabrication of a RP-Based Biomimetic Grafting Material for Bone Tissue Engineering

Three-dimensional (3D) highly porous poly (DL-lactic-co-glycolic acid)/tricalcium phosphate (PLGA/TCP) scaffolds were fabricated using a rapid prototyping technique (RP). The biopolymer carriers (4mm×4mm×4mm) subsequently were coated with collagen type I (Col) to produce PLGA/TCP/Col composites and utilized as an extracellular matrix for a cell-based strategy of bone tissue engineering. Autologous bone marrow stromal cells (BMSCs) harvested from New Zealand white rabbits were cultured under an osteogenic condition (BMSCs-OB) followed by seeding into the structural highly porous PLGA/TCP/Col composites (i.e. PLGA/TCP/Col/BMSCs-OB). Scanning electron microscopy observation found that the RP-based scaffolds had appropriate microstructure, controlled interconnectivity and high porosity. Modification of the scaffolds with collagen type I (PLGA/TCP/Col) essentially increased the affinity of the carriers to seeding cells, and PLGA/TCP/Col composites were well biocompatible with BMSCs-OB. The PLGA/TCP/Col/BMSCs-OB constructs were then subcutaneously implanted in the back of rabbits compared to controls with autologous BMSCs suspension and carriers alone. As a result, histological new bone formation was observed only in the experimental group with PLGA/TCP/Col/BMSCs-OB constructs 8 weeks after implantation. In the control group with scaffold alone only biodegradation of the carriers was found. Therefore, these results validate our bio-manufacturing methods for a new bone graft substitute.

Uso de polímeros em formulações para preservação de Pectobacterium atrosepticum e Ralstonia solanacearum

A sobrevivência de Pectobacterium atrosepticum e de Ralstonia solanacearum foi avaliada em veículo à base de goma xantana (GX), um polímero biológico, e de goma xantana acrescida de polivinilpirrolidona (PVP), um polímero sintético. As culturas, após crescimento até 10(11) ufc mL-1 foram injetadas junto a essas formulações e a sobrevivência avaliada em diferentes condições de armazenamento: em temperatura ambiente, em refrigerador (4ºC) e em freezer (-20ºC), por 36 meses. A concentração de células viáveis foi realizada através de diluições seriadas. A patogenicidade foi avaliada em plantas hospedeiras e em iscas. Os resultados permitem observar que a concentração de células viáveis decresceu ao longo do tempo, mantendo-se entre 10³ e 10(4) ufc mL-1 ao final de três anos, exceto para a formulação à base de GX e armazenamento à -20°C, que se mostrou ineficiente para ambas as bactérias. Conclui-se, que os polímeros avaliados mostraram-se eficientes em preservar e manter as características bioquímicas e fisiológicas das bactérias Pectobacterium atrosepticum e de Ralstonia solanacearum.

Assessment of polymers for the formulation of legume inoculants

The survival of the Bradyrhizobium elkanii strains SEMIA 587 and SEMIA 5019 ( = 29W) used for soybean inoculation was evaluated in the biopolymer carrier xanthan together with Jatai gum for up to eight months of storage. Peat carrier was used for comparison. The synthetic polymers polyvinylpyrrolidone (PVP) and polyethyleneglycol (PEG) were added to the broth cultures which were injected into the peat and polymer carriers. Best results were obtained after the fourth month of storage with the mixture of the gums plus PVP broth, or without the additive, and these were superior to the gums plus PEG and to the peat carrier with or without PVP.

Dextran–estrone conjugate: synthesis and in vitro release study

A novel hormone conjugate has been prepared by a coupling reaction between modified estrone and dextran. In order to provide a suitable reactive estrone derivative for coupling with dextran and a spacer between the drug carrier and the hormone, the steroidal sex hormone was succinylated by reaction with succinic anhydride. Subsequently, the carboxylic acid terminal of succinylated estrone was further reacted with thionyl chloride to replace the hydroxy group with chlorine to make a better leaving group. The ester bond was employed as labile linkage between the hormone and the biopolymer carrier backbone so that the coupled estrogen could be released from the conjugate via ester hydrolysis. Structures of the modified estrone and dextran–estrone conjugate were determined by elemental analysis and by FTIR, 1H and 13C NMR spectroscopies. The degree of substitution (D.S.) per anhydroglucose (AHG) unit was 0.33 (11.0 mol-% of estrone moieties), as calculated from the 1H NMR spectrum. In vitro hydrolysis of the conjugate in aqueous phosphate buffer/ethanol solutions at pH 8.0 and 7.4 and 37°C released estrone was completed within a few days and followed zero-order kinetics.