Continuous Drug Release by Sea Anemone Nematostella vectensis Stinging Microcapsules

Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery.     

Mucoadhesive Chitosan Electrospun Nanofibers Containing Tetracycline and Triamcinolone as a Drug Delivery System

The mucoadhesive Chitosan (CS) nanofibers as a drug delivery system were developed. Chitosan was modified via the immobilization of thiol groups from L-cysteine as a mucoadhesive reagent. The mucoadhesive properties of the chitosan nanofibers were evaluated by tensiometer set and via tensile studies. Drug and mucoadhesive agent loading lead to decrease diameters and increased porous of nanofibers. The release of Tetracycline (Tet) and Triamcinolone (Tri) were increased with increasing immersion time and it became constant at long immersion times. Mucoadhesion studies were done at pH 2–7 and in pH 6 maximum mucoadhesive properties observed. Release studies demonstrated a sustained release of both drug continued up to 48 hours. Microbial studies were performed on the nanofibers. The drug delivery system represented a novel tool for improve the therapeutic efficacy of various drugs that are poorly absorbed from the gastrointestinal tract. Also it is an efficient system for treatment of oral ulceration.     

Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail.     

pH sensitive and controlled release system based on cellulose nanofibers-poly vinyl alcohol hydrogels for cisplatin delivery

Delivery of chemotherapy drugs, such as cisplatin, with controlled manner is a significant area of research in cancer treatment. The main purpose of this study was to investigate the in-vitro release of cisplatin from pH sensitive and controlled release hydrogels based on cellulose nanofibers (CNFs) and poly(vinyl alcohol) (PVA). Various hydrogels with different amounts of CNFs were prepared. This novel drug delivery system was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses. By in-vitro experiments the influence of CNFs contents and pH of the release media on the release rate of the drug were investigated. According to the results, the hydrogel containing 1 wt% CNFs in the release media with the pH of 7.4, efficiently sustained the drug release and so can cause to the reduction of side effects of drug. By fitting the experimental data with various kinetic models it was concluded that the release mechanism is best fitted by Korsmeyer-Peppas kinetic model suggesting the diffusion controlled release mechanism. The prepared hydrogel system is suitable for delivery of cisplatin in the small intestine with a controlled manner.     

茶多糖对阿霉素抑制肺癌A549细胞增殖作用的影响

肺癌是全世界目前发病率和死亡率最高的癌症之一,当前治疗恶性肿瘤的主要手段之一是化疗,阿霉素是临床常用的化疗药物,然而该药物毒性较大,长期使用可发生剂量依赖性的不可逆的心肌病变、骨髓抑制等,同时其多药耐药性的存在也使它在临床应用受到一定限制。为了减少阿霉素的毒副作用,通过体外培养人肺癌A549细胞,将茶叶提取物茶多糖与阿霉素联用,加入A549细胞,24 h后以噻唑蓝(MTT)法检测细胞存活率。结果表明,当阿霉素质量浓度为3 mg·L~(-1)时,对肺癌A549细胞的抑制效果最明显;不同浓度茶多糖与1、2、3 mg·L~(-1)阿霉素联用,以2 mg·L~(-1)阿霉素与6 mg·L~(-1)茶多糖联用时对肺癌A549细胞的抑制效果最明显,且优于单独使用3 mg·L~(-1)阿霉素的效果。阿霉素可诱导A549细胞凋亡,茶多糖与阿霉素联用可减少阿霉素的使用剂量,增强阿霉素对肺癌A549细胞的增殖抑制作用。     

Stimuli-responsive polymers and their applications in nanomedicine

This review focuses on smart nano-materials built of stimuli-responsive (SR) polymers and will discuss their numerous applications in the biomedical field. The authors will first provide an overview of different stimuli and their corresponding, responsive polymers. By introducing myriad functionalities, SR polymers present a wide range of possibilities in the design of stimuli-responsive devices, making use of virtually all types of polymer constructs, from self-assembled structures (micelles, vesicles) to surfaces (polymer brushes, films) as described in the second section of the review. In the last section of this review the authors report on some of the most promising applications of stimuli-responsive polymers in nanomedicine. In particular, we will discuss applications pertaining to diagnosis, where SR polymers are used to construct sensors capable of selective recognition and quantification of analytes and physical variables, as well as imaging devices. We will also highlight some examples of responsive systems used for therapeutic applications, including smart drug delivery systems (micelles, vesicles, dendrimers...) and surfaces for regenerative medicine.     

Fabrication of electrospun antimicrobial nanofibers containing metronidazole using nanospider technology

Nanospider technology as a modified electrospinning technique was used for the fabrication of electrospun nanofibers based on poly(vinyl alcohol) (PVA)/poly(ethylene oxide) (PEO) blend as drug delivery system (DDS) for metronidazole (MTZ) as an antimicrobial drug. Electrospun PVA/PEO/MTZ composite nanofibers were stabilized against disintegration in water by heating in oven at 110°C, or by soaking in isopropyl alcohol for 6 hrs. Incorporation of MTZ into electrospun nanofibers was confirmed by SEM, FT-IR spectra and TGA. The drug release results showed that the burst release was suppressed with stabilized electrospun nanofibers compared with non-stabilized ones. Electrospun PVA/PEO/MTZ composite nanofibers exhibited remarkable antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger, Penicillium notatum and Aspergillus flavus which varies with the species of the tested organisms.     

Development of a platform of antibody-presenting liposomes

Antibody-presenting liposomes present high interest as drug delivery systems. The association of antibodies to liposomes is usually realized by covalent coupling of IgGs or their antigen-binding fragments to lipid polar head groups by means of hetero-bifunctional crosslinkers. We present here an original platform of IgG-presenting liposomes which is based on a fusion protein between Annexin-A5 (Anx5) and the IgG-binding ZZ repeat derived from Staphylococcus aureus protein A. The Anx5ZZ fusion protein acts as a bi-functional adaptor that anchors IgGs to liposomes in a non covalent and highly versatile manner. The interactions between IgGs, Anx5ZZ and liposomes were characterized by PAGE, dynamic light scattering and fluorescence quenching assays, establishing that binding of Anx5ZZ to IgGs and of Anx5ZZ-IgG complexes to liposomes is complete with stoichiometric amounts of each species. We found that the sequence of assembly is important and that Anx5ZZ-IgG complexes need to be formed first in solution and then adsorbed to liposomes in order to avoid aggregation. The targeting capacity of Anx5ZZ-IgG-functionalized liposomes was demonstrated by electron microscopy on an ex vivo model system of atherosclerotic plaques. This study shows that the Anx5ZZ adaptor constitutes an efficient platform for functionalizing liposomes with IgGs. This platform may present potential applications in molecular imaging and drug delivery.     

Alkylation of spiropyran moiety provides reversible photo-control over nanostructured soft materials

The purpose of this study was to create a light responsive nanostructured liquid crystalline matrix using a novel alkylated spiropyran photochromic molecule (spiropyran laurate, SPL) as a light activated drug delivery system. The liquid crystal matrix, prepared from phytantriol, responds reversibly to changes in photoisomerism of SPL on irradiation, switching between the bicontinuous cubic and the reversed hexagonal liquid crystal structures, a change previously shown to dramatically alter drug release rate. In contrast, the non-derivatized spiropyran and spirooxazine photochromic compounds do not sufficiently disrupt the matrix on isomerization to induce the phase change. Thus, novel alkylated spiropyran has the potential to be an effective agent for use in liquid crystalline systems for reversible 'on-demand' drug delivery applications.     

The Structural Characteristics of Seaweed Polysaccharides and Their Application in Gel Drug Delivery Systems

In recent years, researchers across various fields have shown a keen interest in the exploitation of biocompatible natural polymer materials, especially the development and application of seaweed polysaccharides. Seaweed polysaccharides are a multi-component mixture composed of one or more monosaccharides, which have the functions of being anti-virus, anti-tumor, anti-mutation, anti-radiation and enhancing immunity. These biological activities allow them to be applied in various controllable and sustained anti-inflammatory and anticancer drug delivery systems, such as seaweed polysaccharide-based nanoparticles, microspheres and gels, etc. This review summarizes the advantages of alginic acid, carrageenan and other seaweed polysaccharides, and focuses on their application in gel drug delivery systems (such as nanogels, microgels and hydrogels). In addition, recent literature reports and applications of seaweed polysaccharides are also discussed.     

Low Molecular Weight Chitosan–Insulin Polyelectrolyte Complex: Characterization and Stability Studies

The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs) on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC) in a reverse micelle (RM) system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity.     

Polyethylenimine-based amphiphilic core-shell nanoparticles: study of gene delivery and intracellular trafficking

Amphiphilic core-shell nanoparticle, which is composed of a hydrophobic core and a branched polyethylenimine (PEI) shell, has been designed and synthesized as a novel gene delivery nanocarrier. In our previous study, we demonstrated that the core-shell nanoparticle was not only able to efficiently complex with plasmid DNA (pDNA) and protect it against enzymatic degradation, but also three times less cytotoxic, and threefold more efficient in gene transfection than branched 25 kDa PEI. This paper reports our further studies in the following three aspects: (1) the ability of the PEI-based nanoparticles to deliver gene in various mammalian cell lines; (2) intracellular distributions of the nanoparticles and their pDNA complexes in HeLa cells; and (3) incorporation of nuclear targeting agent into the nanoparticle/pDNA complexes to enhance the nuclear targeting ability. The PEI-based nanoparticles were able to transfect both human and non-human cell lines and their transfection efficiencies were cell-dependent. Within our four tested cell lines (MCF-7, BEL 7404, C6 and CHO-K1), gene transfer using PEI-based core-shell nanoparticles displayed gene expression levels comparable to, or even better than, the commercial Lipofectamine? 2000. Confocal laser scanning microscopy showed that the nanoparticles and their pDNA complexes were effectively internalized into the HeLa cells. The in vitro time series experiments illustrated that both the nanoparticle/pDNA complexes and PEI-based nanoparticles were distributed in the cytoplasmic region after transfection for 10 and 60 min, respectively. Nuclear localization was also observed in both samples after transfection for 20 and 60 min, respectively. Incorporation of the high mobility group box 1 (HMGB1) protein for nuclear targeting has also been demonstrated with a simple approach: electrostatic complexation between the PEI-based nanoparticles and HMGB1. In the in vitro transfection study in MCF-7 cells, the expression level of the firefly luciferase gene encoded by the pDNA increased remarkably by up to eightfold when the HMGB1 protein was incorporated into the nanoparticle/pDNA complexes. Our results demonstrate that the PEI-based core-shell nanoparticles are promising nanocarriers for gene delivery.     

A novel purification method of artemisinin from Artemisia annua

Treatment of uncomplicated malaria relies heavily on the sesquiterpene lactone artemisinin (ART), derived from the Chinese herb Artemisia annua. It is currently used as the first line treatment in the form of ART combination therapies in which different ART derivatives are combined with a non ART-like drug, which displays a different mechanism of action. This treatment regime is prescribed by the WHO in order to (1) effectively treat uncomplicated malaria and (2) to reduce the risk that drug resistance will develop. Considering the importance of ART in this treatment regime, various methods have been developed to increase the global production of ART. These methods include: large scale solvent extraction and purification from high yielding A. annua varieties, chemical/semi-chemical synthesis of artemisinin, and genetic engineering of unrelated organisms to produce ART in high quantities. Currently most of the commercial approaches to produce ART are based on solvent extraction and purification from the plant material. Classical extraction solvents include hexane or petroleum ether while ethanol, which is a more polar solvent, has recently been shown to be equally efficient. We developed a purification method from an ethanolic extract by using a diatomite-based purification protocol. Various volumes and ratios of solvents and diatomite were tested which resulted in ≥98% pure ART with a total recovery of around 60%. Our protocol for the isolation of ART may form a commercial scale alternative as it is both economically attractive due to the small amounts of purification materials needed and also environmentally friendlier than the methods previously described.     

Chitin and Chitosan as Multipurpose Natural Polymers for Groundwater Arsenic Removal and As2O3 Delivery in Tumor Therapy

Chitin and chitosan are natural polysaccharide polymers. These polymers have been used in several agricultural, food protection and nutraceutical applications. Moreover, chitin and chitosan have been also used in biomedical and biotechnological applications as drug delivery systems or in pharmaceutical formulations. So far, there are only few studies dealing with arsenic (As) removal from groundwater using chitin or chitosan and no evidence of the use of these natural polymers for arsenic trioxide (As₂O₃) delivery in tumor therapy. Here we suggest that chitin and/or chitosan might have the right properties to be employed as efficient polymers for such applications. Besides, nanotechnology offers suitable tools for the fabrication of novel nanostructured materials of natural origin. Since different nanostructured materials have already been employed successfully in various multidisciplinary fields, we expect that the integration of nanotechnology and natural polymer chemistry will further lead to innovative applications for environment and medicine.     

Chitin and Chitosan: Prospective Biomedical Applications in Drug Delivery,Cancer Treatment,and Wound Healing

Chitin and its derivative chitosan are highly abundant polymers in nature, appearing in both the shells and exoskeletons of various marine and non-marine species. Since they possess favorable properties, such as biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, they have gained recent attention due to their enormous potential biomedical applications. The polycationic surface of chitosan enables it to form hydrogenic and ionic bonds with drug molecules, which is one of its most useful properties. Because chitosan is biocompatible, it can therefore be used in drug delivery systems. The development of chitosan-based nanoparticles has also contributed to the significance of chitin as a drug delivery system that can deliver drugs topically. Furthermore, chitin can be used in cancer treatment as a vehicle for delivering cancer drugs to a specific site and has an antiproliferative effect by reducing the viability of cells. Finally, chitosan can be used as a wound dressing in order to promote the faster regeneration of skin epithelial cells and collagen production by fibroblasts. As discussed in this review, chitin and chitosan have diverse applications in the medical field. Recognizing the biomedical applications of these two polymers is essential for future research in tissue engineering and nanobiotechnology.     

Carrageenan: Drug Delivery Systems and Other Biomedical Applications

Marine resources are today a renewable source of various compounds, such as polysaccharides, that are used in the pharmaceutical, medical, cosmetic, and food fields. In recent years, considerable attention has been focused on carrageenan-based biomaterials due to their multifunctional qualities, including biodegradability, biocompatibility, and non-toxicity, in addition to bioactive attributes, such as their antiviral, antibacterial, antihyperlipidemic, anticoagulant, antioxidant, antitumor, and immunomodulating properties. They have been applied in pharmaceutical formulations as both their bioactive and physicochemical properties make them suitable biomaterials for drug delivery, and recently for the development of tissue engineering. This article provides a review of recent research on the various types of carrageenan-based biomedical and pharmaceutical applications.     

Cloning and Characterization of a Novel Alginate Lyase from Paenibacillus sp. LJ-23

As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied in a drug delivery system. In this paper, a novel alginate lyase, Algpt, was cloned and characterized from a marine bacterium, Paenibacillus sp. LJ-23. The purified enzyme was composed of 387 amino acid residues, and had a molecular weight of 42.8 kDa. The optimal pH of Algpt was 7.0 and the optimal temperature was 45 °C. The analysis of the conserved domain and the prediction of the three-dimensional structure indicated that Algpt was a novel alginate lyase. The dominant degradation products of Algpt on alginate were AOS dimer to octamer, depending on the incubation time, which demonstrated that Algpt degraded alginate in an endolytic manner. In addition, Algpt was a salt-independent and thermo-tolerant alginate lyase. Its high stability and wide adaptability endow Algpt with great application potential for the efficient preparation of AOS with different sizes and AOS-based products.     

Coating Cellulosic Materials with Graphene for Selective Absorption of Oils and Organic Solvents from Water

Development of efficient and eco-friendly sorbents used for selective oil removal after oil spill disasters is one of the main topics in environmental science. By using various cellulosic materials coated with graphene flakes, using simple, one-step dip-coating method, it was possible to manufacture environmentally friendly, selective oil sorbents. The cellulosic materials of different yarn size and distribution such as cotton roving, gauze, fabric, and cellulosic wipe and Whatman filter paper were chosen. The scanning electron microscopy showed that simple dip-coating of any cellulosic materials into graphene dispersion creates a uniformly distributed nanomaterial coating. The wetting tests confirmed that the coating endowed cellulosic materials with hydrophobic properties, regardless of their initial yarn distribution and purity. Moreover, the water repellent samples were simultaneously highly sorptive towards oils and organic solvents. Sorption tests performed for a representative group of organic solvents and oils have shown that depending on cellulosic material the oil sorption capacity varied from 4 g/g to 33 g/g for cotton fabric and roving, respectively. Moreover, the absorption selectivity of chloroform versus water exceeded 90 % for each sample and reached over 99 % for the graphene coated cotton roving and gauze. Finally, the recyclability tests have shown that graphene coated materials are less fragile for reuse than naturally hydrophobic sorbents.     

Preparation of Alginate-Based Biomaterials and Their Applications in Biomedicine

Alginates are naturally occurring polysaccharides extracted from brown marine algae and bacteria. Being biocompatible, biodegradable, non-toxic and easy to gel, alginates can be processed into various forms, such as hydrogels, microspheres, fibers and sponges, and have been widely applied in biomedical field. The present review provides an overview of the properties and processing methods of alginates, as well as their applications in wound healing, tissue repair and drug delivery in recent years.     

Characteristics of Marine Biomaterials and Their Applications in Biomedicine

Oceans have vast potential to develop high-value bioactive substances and biomaterials. In the past decades, many biomaterials have come from marine organisms, but due to the wide variety of organisms living in the oceans, the great diversity of marine-derived materials remains explored. The marine biomaterials that have been found and studied have excellent biological activity, unique chemical structure, good biocompatibility, low toxicity, and suitable degradation, and can be used as attractive tissue material engineering and regenerative medicine applications. In this review, we give an overview of the extraction and processing methods and chemical and biological characteristics of common marine polysaccharides and proteins. This review also briefly explains their important applications in anticancer, antiviral, drug delivery, tissue engineering, and other fields.