Alginate: properties and biomedical applications

Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.     

On physical and antibacterial properties and drug release behavior of poly(vinyl alcohol) hydrogels: effect of drug loaded chitosan nanoparticles

This paper deals with influence of chitosan nanoparticles (CNPs) loaded by tetracycline, as a drug, on the physico-mechanical and antibacterial properties as well as drug release behavior of poly(vinyl alcohol), PVA, hydrogels prepared by electron beam irradiation. The formation of spherical chitosan particles in nanoscale size prepared by an ionic gelation method was confirmed by FTIR and UV spectroscopy, and scanning electron microscopy analyses. The drug release kinetic studies from drug loaded chitosan nanoparticles (DLCNPs) at pH = 7.4 revealed a linear and steady release behavior over long period of time. The theoretical analysis of the swelling kinetic data, using Peppas’s model showed that the swelling kinetic is governed by Fickian diffusion for all the prepared hydrogels, however, the water diffusion coefficient, and therefore, the swelling content were lower for the hydrogels loaded with DLCNPs as compared to the ones with the neat drug. In agreement with these results, the hydrogels containing DLCNPs exhibited a more controlled drug release behavior with significantly stronger antibacterial activity. The tensile mechanical properties of the hydrogels not affected by the DLCNPs were found to be suitable for wound dressing applications.     

Development of ultrafine chitosan fibers through modified wetspinning technique

Chitosan has been extensively exploited in biomaterials research because of easy tailorable properties. Chitosan fibers are produced through either wetspinning or electrospinning. However, it is difficult to produce few microns fibers using either of these techniques. Present study focuses on production of ultrafine chitosan fibers through modified wetspinning technique by injecting homogenous chitosan solution through a very fine hole of silicone tube into either sodium tripolyphosphate (STPP) or sodium hydroxide (NaOH) bath by applying positive pressure. The gelation behavior of the chitosan was evaluated with STPP and NaOH solution through rheological study for comparative spinnability of chitosan in STPP and NaOH bath. Although gel strength of chitosan–NaOH system (240 Pa) was four times higher than that of chitosan–STPP system, gel breakdown rate was higher in previous case. From Fourier infrared spectroscopy (FTIR) analysis, ionic cross‐linking between TPP and chitosan molecules in chitosan–TPP fibers was confirmed. Scanning electron micrographs showed fine chitosan fibers with average diameter of ～ 10 μm. These nonwoven fibers/scaffolds with interconnected porosity may find potential biomedical applications. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

晚香玉香精壳聚糖纳米粒的制备及表征

以三聚磷酸钠(TPP)为交联剂,通过离子凝胶法制备晚香玉香精壳聚糖纳米粒。研究了壳聚糖质量浓度、香精质量浓度、乳化剂与香精的质量比及反应时间对晚香玉香精壳聚糖纳米粒粒径的影响,并采用动态激光光散射仪(DLS)、透射电镜(TEM)、红外光谱仪(IR)及热重分析仪(TGA)对其结构及性能进行了表征。结果表明,当壳聚糖质量浓度为1.71 g/L、香精质量浓度为1.72 g/L、m(乳化剂)∶m(香精)=1∶2、反应时间为1 h时,制备的晚香玉香精壳聚糖纳米粒平均粒径为138 nm,粒径分布系数为0.100,香精装载量达28.4%,能减缓高温下香精的释放速率。     

Preparation of nanoparticles composed of chitosan and its derivatives as delivery systems for macromolecules

Three different kinds of nanoparticles for paracellular transport were prepared using a simple and mild ionic‐gelation method. Sodium tripolyphosphate (TPP) as crosslinking agent was added into three kinds of solutions, which were chitosan solution, physical blending solution of chitosan, and glycidyl trimethylammonium chloride (GTMAC), and O‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (O‐HTCC) solution respectively. O‐HTCC was synthesized by coupling of GTMAC to chitosan whose functional groups of the NH₂ groups were protected. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, photon correlation spectroscopy, and zeta potential measurement. The results showed that increasing TPP concentration promoted the size of chitosan nanoparticles, a decrease in the size of O‐HTCC nanoparticles incurred on the contrary. The size of O‐HTCC nanoparticles is slightly bigger than that of pure chitosan nanoparticles, and smaller than that of physical blending nanoparticles (PBN). Bovine serum albumin (BSA), as a model protein drug, was incorporated into the nanoparticles. Compared with chitosan nanoparticles and PBN, high BSA loading efficiency (87.5%) and loading capacity (99.5%) are achieved by quaternized chitosan (O‐HTCC) nanoparticles, and the release profile of BSA from nanoparticles has an obvious burst effect and a slowly continuous release phase followed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers

Hydrophilic nanoparticulate carriers have important potential applications for the administration of therapeutic molecules. The recently developed hydrophobic-hydrophilic carriers require the use of organic solvents for their preparation and have a limited protein-loading capacity. To address these limitations a new approach for the preparation of nanoparticles made solely of hydrophilic polymers is presented. The preparation technique, based on an ionic gelation process, is extremely mild and involves the mixture of two aqueous phases at room temperature. One phase contains the polysaccharide chitosan (CS) and a diblock copolymer of ethylene oxide and propylene oxide (PEO-PPO) and, the other, contains the polyanion sodium tripolyphosphate (TPP). Size (200–1000 nm) and zeta potential (between +20 mV and +60 mV) of nanoparticles can be conveniently modulated by varying the ratio CS/PEO-PPO. Furthermore, using bovine serum albumin (BSA) as a model protein it was shown that these new nanoparticles have a great protein loading capacity (entrapment efficiency up to 80% of the protein) and provide a continuous release of the entrapped protein for up to 1 week. © 1997 John Wiley & Sons, Inc.     

Fabrication of galactosylated chitosan–5‐fluorouracil acetic acid based nanoparticles for controlled drug delivery

In this study, a novel type of macromolecular prodrug, N‐galactosylated chitosan (GC)?5‐fluorouracil acetic acid (FUA) conjugate based nanoparticles, was designed and synthesized as a carrier for hepatocellular carcinoma drug delivery. The GC–FUA nanoparticles were produced by an ionic crosslinking method based on the modified ionic gelation of tripolyphosphate with GC–FUA. The structure of the as‐prepared GC–FUA was characterized by Fourier transform infrared and ¹H‐NMR analyses. The average particle size of the GC–FUA nanoparticles was 160.1 nm, and their drug‐loading content was 21.22 ± 2.7% (n = 3). In comparison with that of the freshly prepared nanoparticles, this value became larger after 7 days because of the aggregation of the GC–FUA nanoparticles. An in vitro drug‐release study showed that the GC–FUA nanoparticles displayed a sustained‐release profile compared to 5‐fluorouracil‐loaded GC nanoparticles. All of the results suggest that the GC–FUA nanoparticles may have great potential for anti‐liver‐cancer applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42625.     

可生物降解药物载体——纳米/亚微米壳聚糖微球的制备及性能

利用聚电解质的离子凝胶反应,在溶液中壳聚糖为聚阳离子电解质与带反相电荷的聚阴离子三聚磷酸钠(TPP)发生离子凝胶反应,在合适的浓度和适当的搅拌速度下,得到亚微米级的壳聚糖微球。利用环己烷作为油相,以壳聚糖溶液为水相,配制澄清透明的W/O反相微乳清液,滴加质量浓度为5mg/mL的TPP溶液于已配制好的微乳清液中,制得纳米级壳聚糖微球。采用上述两种方法制得的纳米/亚微米壳聚糖微球用作生物降解药物载体,载药实验结果表明,释放初期无明显暴释现象,具有良好的药物缓释作用。     

磁性壳聚糖微球的研究进展

磁性氧化铁纳米粒子（Fe3O4,γ-Fe2O3等）因具有尺寸小、超顺磁性和低毒性等特点,已经引起了生物化工、医药工业研究领域的广泛关注。磁性壳聚糖微球具有表面非常光滑的球形结构。近年来,已经制备出了平均粒径在10～2.5×105 nm之间的磁性壳聚糖微球,并在生物医药、食品工程和污水处理等许多领域已经取得了初步的应用,特别是在污水处理和酶固定化领域。本文综述了近年来磁性氧化铁纳米粒子和磁性壳聚糖微球的制备方法、磁性壳聚糖微球的改性方法及应用的最新研究成果。     

Investigation of polyvinyl alcohol nanocomposite hydrogels containing chitosan nanoparticles as wound dressing

Polymeric hydrogels, water-swollen 3?D networks of the polymers, have found wide ranges of applications in the medical fields, such as wound care and wound dressing, in order to prevent infections. Prevention from microorganisms transfer in to the wounds is one of the ideal wound dressing duties of polyvinyl alcohol (PVA) hydrogels. In this study, at the start, under optimal conditions, nanoparticles of chitosan using ionotropic gelation method were synthesized and in the next step in order to achieve particles with a minimum size, they were evaluated by scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). Then after to obtain a wound dressing with preferable properties, nanocomposite hydrogels using a combination of PVA and 5, 10 and 15?wt% chitosan nanoparticles were prepared through freezing-thawing cycles. The necessary features of PVA nanocomposite hydrogels for wound dressing were investigated. The dispersion state of nanoparticles and structure of samples were evaluated by SEM microscopy. The nanoparticle size and the nanoparticle size distribution of chitosan was determined using the dynamic light scattering test at the nanometer scale. The physical behavior of hydrogels such as swelling and gel fraction was studied and their mechanical properties were investigated by compressive test. Finally the antimicrobial test and biocompatibility as cell viability were carried out. The results proved that the PVA nanocomposite hydrogels fulfill the requirements of a good wound dressing with desirable characteristics such as favorable swelling and acceptable strength, excellent barrier against microbial penetration.     

Design of a drug delivery system based on poly(acrylamide‐co‐acrylic acid)/chitosan nanostructured hydrogels

To obtain biodegradable materials for biomedical applications, new biopolymeric hydrogels based on blends of polyacrylamide nanoparticles and chitosan have been prepared. In this work, we have studied the behavior of the diffusion of ascorbic acid (V‐C) from poly(acrylamide‐co‐acrylic acid)/chitosan nanostructured hydrogels. The process involves the synthesis of nanoparticles of polyacrylamide by inverse microemulsion polymerization and their complexation with chitosan dissolved in an acrylic acid aqueous solution. We have studied the effect of the concentration of the polyacrylamide nanoparticles, which are crosslinked with N,N′‐methylenebisacrylamide, in the delivery of V‐C. The results indicate that the drug delivery operates by a non‐Fickian mechanism. Also, we have obtained the diffusion coefficient for V‐C in gels for different nanoparticle concentrations, using a modified form of Fick's second law that takes into account dimensional changes in the hydrogels during drug release. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

FUNCTIONALIZED CHITOSAN AND ITS USE IN PHARMACEUTICAL,BIOMEDICAL, AND BIOTECHNOLOGICAL RESEARCH

Hybrids of natural polymers with synthetic polymers are of great interest because of their application as biomedical and biodegradable materials. One of the natural polymers that has attracted much recent attention is chitosan, a polysaccharide obtained by alkaline deacetylation of chitin, exhibiting excellent biological properties such as biodegradability in the human body and immunological, antibacterial, and wound-healing activities. Chitosan has also been found to be a good candidate as a support material for gene delivery, cell culture, and tissue engineering. In this review we have presented the current applications of the various types of chitosan derivatives synthesized in the fields of drug delivery, tissue engineering, wound healing, antimicrobials, biotechnology, pharmaceutics, and cosmetics.     

Hybrid Nanoarchitectonics of Chitosan-Cerium Oxide Nanoparticles for Anticancer Potentials

The aim of this study was to synthesize green cerium oxide nanoparticles (CeO₂–NPs) and coat them with chitosan polymers to increase bioavailability and their effectiveness in anti-cancer studies. For the synthesis of CeO₂–NPs, aqueous rosemary leaf extract (RLE) was used as a reducing and stabilizing agent, and after characterizing the nanoparticles (DLS and XRD), a coating of chitosan around the nanoparticles (CeCh–NPs) was created by ionic gelation method. After characterizing (DLS, Zeta potential, FTIR and FESEM) and confirming the presence of nanoparticles, its toxicity effects were evaluated by MTT method and its pro-apoptotic effects were evaluated by qPCR (Caspase 3 and 9) and flow cytometric analysis. CeO₂–NPs were formed with uniform dispersion (PDI: 0.25) in nanometer dimensions (184.84 nm) and after coating, their size increase to 202.35 nm was confirmed by DLS method. The CeCh–NPs were spherical, stable (ζ potential:?+?35.4 mV) and uniformly dispersed (PDI: 0.27). The median concentrations of nanoparticles against AGS, A459, PC3 and HFF cells were reported to be about 156.02, 169.1, 155.8 and 307.5 μg/ml. Increased expression of caspase 3 and 9 genes as well as increased percentage of SubG1 phase cells in flow cytometry confirmed the occurrence of apoptosis in treated cells. The results of this study confirmed the anticancer properties of CeCh–NPs by relying on the apoptosis process.

     

Preparation of nanoparticles by the self-organization of polymers consisting of hydrophobic and hydrophilic segments: Potential applications

This review describes the preparation of core-corona type polymeric nanoparticles and their applications in various technological and biomedical fields. Over the past two decades, we have studied the synthesis and clinical applications of core-corona polymeric nanoparticles composed of hydrophobic polystyrene and hydrophilic macromonomers. These nanoparticles were utilized as catalyst carriers, carriers for oral peptide delivery, virus capture agents, and vaccine carriers, and so on. Moreover, based on this research, we attempted to develop novel biodegradable nanoparticles composed of hydrophobic poly(γ-glutamic acid) (γ-PGA) derivatives (γ-hPGA). Various model proteins were efficiently entrapped on/into the nanoparticles under different conditions: encapsulation, covalent immobilization, and physical adsorption. The encapsulation method showed the most promising results for protein loading. It is expected that biodegradable γ-hPGA nanoparticles can encapsulate and immobilize various biomacromolecules. Nanoparticles consisting of hydrophobic and hydrophilic segments have great potential as multifunctional carriers for pharmaceutical and biomedical applications, such as drug, protein, peptide or DNA delivery systems.     

Physicochemical characterization and antioxidant activity of quercetin‐loaded chitosan nanoparticles

Quercetin is an abundant flavonoid in food plants with numerous biological activities and widely used as a potent antioxidant. Being sparingly soluble in water and subject to degradation in aqueous intestinal fluids, the absorption of quercetin is limited upon oral administration. In the present study, chitosan nanoparticles and quercetin‐loaded nanoparticles were prepared based on the ionic gelation of chitosan with tripolyphosphate anions. The encapsulation of quercetin in the chitosan nanoparticles were confirmed by differential scanning calorimetry, X‐ray powder diffractometry, Fourier transformed infrared spectroscopy, ultraviolet‐visible spectrum, and fluorescence spectrum. The morphology of the nanoparticles was characterized by atomic force microscopy. The antioxidant activity of the quercetin‐nanoparticles was also evaluated in vitro by two different methods (free radical scavenging activity test and reducing power test), which indicates that inclusion of quercetin in chitosan nanopaticles may be useful in improving the bioavailabilty of quercetin. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

Preparation and characterization of venlafaxine hydrochloride‐loaded chitosan nanoparticles and in vitro release of drug

The venlafaxine hydrochloride (VHL)‐loaded chitosan nanoparticles were prepared by ionic gelation of chitosan (CS) using tripolyphosphate (TPP). The nanoparticles were characterized using FTIR, differential scanning calorimetry, X‐ray diffraction, dynamic light scattering, transmission electron microscopy, and X‐ray photoelectron spectroscopy. The effect of concentration of CS, polyethylene glycol (PEG), VHL and CS/TPP mass ratio on the particle size and zeta potential of nanoparticles was examined. The particle size of CS/TPP nanoparticles and VHL‐loaded CS/TPP nanoparticles was within the range of 200–400 nm with positive surface charge. In the case of VHL‐loaded nanoparticles and PEG‐coated CS/TPP nanoparticles, the particle size increases and surface charge decreases with increasing concentration of VHL and PEG. Both placebo and VHL‐loaded CS/TPP nanoparticles were observed to be spherical in nature. PEG coating on the surface of CS/TPP nanoparticles was confirmed by XPS analysis. Maximum drug entrapment efficiency (70%) was observed at 0.6 mg/mL drug concentration. In vitro drug release study at 37°C ± 0.5°C and pH 7.4 exhibited initial burst release followed by a steady release. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

The effects of ionic strength and pH on antibacterial activity of hybrid biosurfactant-biopolymer nanoparticles

The physicochemical properties of nanoparticles (NPs) directly influence the colloidal stability and bio-nano interface, which makes the study of these factors extremely important for NPs applicability. Here, we report the influence of pH and ionic strength in the size, surface charge, and antimicrobial activity of chitosan/rhamnolipid nanoparticles (C/RL-NPs), synthesized by mixing C and RL in the proportion of 1:1, with the dropwise addition of TPP (sodium tripolyphosphate) in the molar ratio of 1:2.5:1.3, respectively. The obtained NPs were resuspended in different solvents to investigate the ionic strength effect on their stability and antimicrobial activity. By decreasing pH and ionic strength, NPs size was reduced while their surface charge increased. Chitosan nanoparticles (C-NPs) remained stable in the presence of TPP at acidic pH and low ionic strength, indicating that the modulation of physicochemical conditions for the crosslinking between the two ionic components was an efficient approach to enhance C/RL-NPs colloidal stability. Thermogravimetric analysis confirmed the interaction between rhamnolipid and chitosan in C/RL-NPs. The antibacterial activity of C/RL-NPs against Staphylococcus aureus increased significantly, demonstrating the importance of investigating size and surface charge to dictate the bioactivity properties of such hybrid natural-based nanomaterial.     

水溶性壳聚糖纳米粒子的制备及其BSA载药性能

为了避免高分子量壳聚糖水溶性差以及增溶剂乙酸可能带来的负面作用,本文选择低分子量水溶性壳聚糖 (WSC)作研究对象,采用三聚磷酸(TPP)作交链剂制备不同WSC/TPP比率的WSC纳米粒子,并用于牛血清白蛋白 (BSA)的释放载体。经测得为球形形貌的纳米粒子空载和载药时粒径、Zeta电位分别在35～190 nm、35～42 mV。红外光谱及X–射线衍射证实了纳米粒子中WSC的氨基与TPP的磷酸基团发生了交联反应。纳米粒子载药性能试验表明在0.05～1 mg/mL范围内随着BSA浓度的增大,纳米粒子的载药量增加而负载率降低。体外释放实验表明水溶性壳聚糖纳米载体对蛋白质药物具有缓释特征。因此,水溶性壳聚糖有望成为新的载体应用于蛋白质药物的控制释放。     

Synthesis and characterization of chitosan-coated magnetite nanoparticles using a modified wet method for drug delivery applications

Abstract

Immobilizing various chemical functionalities on the surfaces of magnetite nanoparticles extends these applications without affecting the overall magnetic properties of the coated nanoparticles. In this study, magnetite nanoparticles have been prepared in the presence of chitosan using a simple modified wet method. Composition, morphology and magnetic properties of the chitosan-coated nanoparticles were investigated. Results showed the formation of coating with various thicknesses on the surfaces of the superparamagnetic nanoparticles. This in turn reduced the magnetization of the nanoparticles to some extent. The least particle size obtained in the presence of chitosan was 10?nm.     

Characterization of novel quaternary chitosan derivative nanoparticles loaded with protein

The objective of this work was to characterize a novel quaternary chitosan derivative [O‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (O‐HTCC)] nanoparticle system. O‐HTCC nanoparticles were prepared with a simple and mild ionic gelation method upon the addition of a sodium tripolyphosphate solution to a low‐molecular‐weight O‐HTCC solution. Highly cationic chitosan nanoparticles were prepared. Bovine serum albumin (BSA), a model protein drug, was incorporated into the nanoparticles. The physicochemical properties of the nanoparticles were determined with transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared analysis, differential scanning calorimetry, and X‐ray diffraction (XRD) patterns. The results showed that increasing the BSA concentration from 1.5 to 2.5 mg/mL promoted the BSA encapsulation efficiency from 57.3% to 87.5% and the loading capacity from 70.2% to 99.5%. Compared with the chitosan nanoparticles, the O‐HTCC nanoparticles had lower burst release. TEM revealed that the BSA‐loaded O‐HTCC nanoparticles were smaller than the O‐HTCC nanoparticles when the BSA concentration was 1.5 mg/mL; SEM showed that the size of the BSA‐loaded O‐HTCC nanoparticles was mostly affected by the BSA concentration, and the increase in size occurred with the concentration increasing. Thermograms and XRD of the BSA‐loaded nanoparticles suggested that polyelectrolyte–protein interactions increased with the BSA concentration increasing and greater chain realignment in the BSA‐loaded nanoparticles. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009