In vitro and in vivo degradation behavior of aqueous-derived electrospun silk fibroin scaffolds

We investigated the in vitro degradation behavior of the electrospun silk fibroin (SF) scaffolds by protease XIV. Phosphate-buffered saline (PBS) without enzyme was used as a control. About 65% of the electrospun SF scaffolds were degraded within 24 d in protease XIV, while almost no scaffolds were degraded in PBS. A great deal of fragments was visible in protease XIV solution. SEM indicated surface erosion of the scaffolds increased during protease degradation with increasing exposure time. FTIR and XRD indicated the crystalline structure of the scaffolds decreased after protease degradation for 24 d, and a degradation mechanism was proposed. Furthermore, the results of the in vivo degradation by implantation in rats showed that the scaffolds were completely degraded in vivo after implantation for 8 weeks and well tolerated by the host animals. The insights gained in this study can serve as a guide to match desired degradation behavior with specific applications for the electrospun SF scaffolds, such as tissue engineering and drug delivery.     

A review on electrospun polymeric nanofibers: Production parameters and potential applications

This review deals with electrospun nanofibers and their applications in several fields. Nanofibers have mainly been produced via electrospinning technique due to the simple, cost-effective, and versatile setup. Electrospinning is defined as a process, which produces fibers from its polymer solutions under exposure of high electric field voltage. The technique needs optimization of several parameters such solution, processing and ambient parameters to refine nanofiber morphology, diameter and porosity. The basic technique has been modified to produce composite fibers and to increase production capacity. Nanofiber characterization methods are summarized with examples. The relation between electrospinning and electrospraying is discussed. Nanofibers have the ability to form highly porous mesh with large surface to volume ratio enhancing its performance for various applications such as water filtration, tissue engineering scaffold, wounds, fiber composites, drug release and protective clothes. Single nanofibers could potentially be used as soft microrobots for drug delivery. Finally, results from modeling and simulations are illustrated.     

Fabrication, in vitro degradation and the release behaviours of poly(DL-lactide-co-glycolide) nanospheres containing ascorbic acid

Ascorbic acid (vitamin C) is essential for preserving optimal health and is used by the body for many purposes. The problem is that ascorbic acid easily decomposes into biologically inactive compounds making its use very limited in the field of pharmaceuticals, dermatological and cosmetics. By encapsulating the ascorbic acid into a polymer matrix it is assumed that its chemical instability can be overcome as well as higher, more efficient and equally distributed concentration throughout extended period of time can be achieved. This paper is describing the process of obtaining poly(dl-lactide-co-glycolide) (DLPLG) nanospheres (110-170 nm) using chemical method with solvent/non-solvent systems where obtained solutions have been centrifuged. The encapsulation of the ascorbic acid in the polymer matrix is performed by homogenisation of water and organic phases. Nanoparticles of the copolymer DLPLG with the different contents of the ascorbic acid have different morphological characteristics, i.e. variable degree of uniformity, agglomeration, sizes and spherical shaping. The degradation of the nanospheres of DLPLG, DLPLG/ascorbic acid nanoparticles and release rate of the ascorbic acid were studied for 8 weeks in a physiological solution (0.9% sodium chloride in water). The samples have been characterised by infrared spectroscopy (IR), scanning electron microscopy (SEM), stereological analysis and ultraviolet (UV) spectroscopy.     

Metallized electrospun polymeric fibers for electrochemical sensors and actuators

Electrospun polymeric fibers present an emerging alternative for the development of flexible electronics, enabling applications in wearable sensors and biosensors for continuous monitoring, and actuators for tissue engineering. The possibility to prepare sub-micrometric polymeric scaffolds, their processing for increasing the conductivity, their modification with different materials, conductive polymers and biomolecules in order to obtain functional flexible electrodes, allows the development of innovative devices for healthcare, and biomedical applications. In this review, the impact of metallized electrospun polymeric fibers in electrochemical (bio)sensors and actuators is discussed. A relation between their structure and functionality is provided, alongside with an overview of the different methods to obtain functional conductive fibers.     

Thermal and hydrolytic degradation of electrospun fish gelatin membranes

The thermal and hydrolytic degradation of electrospun gelatin membranes cross-linked with glutaraldehyde in vapor phase has been studied. In vitro degradation of gelatin membranes was evaluated in phosphate buffer saline solution at 37 °C. After 15 days under these conditions, a weight loss of 68% was observed, attributed to solvation and depolymerization of the main polymeric chains. Thermal degradation kinetics of the gelatin raw material and as-spun electrospun membranes showed that the electrospinning processing conditions do not influence polymer degradation. However, for cross-linked samples a decrease in the activation energy was observed, associated with the effect of glutaraldehyde cross-linking reaction in the inter- and intra-molecular hydrogen bonds of the protein. It is also shown that the electrospinning process does not affect the formation of the helical structure of gelatin chains.     

In vitro degradation and release behavior of porous poly(lactic acid) scaffolds containing chitosan microspheres as a carrier for BMP-2-derived synthetic peptide

To develop a novel tissue engineering scaffold with the capability of controlled releasing BMP-2-derived synthetic peptide, porous poly(lactic acid)/chitosan microspheres (PLA/CMs) composites containing different quantities of chitosan microspheres were prepared by a thermally induced phase separation method. FTIR analysis revealed that there were strong hydrogen bond interactions between the PLA and chitosan component. Introduction of less than 30% CMs (on PLA weight basis) did not remarkably affect the morphology and porosity of the PLA/CMs scaffolds. The compressive strength of the composite scaffolds increased from 0.48 to 0.66 MPa, while the compressive modulus increased from 7.29 to 8.23 MPa as the microspheres' contents increased from 0% to 50%. In vitro degradability investigation indicated that the dissolution of chitosan component was preferential than PLA matrix and the inclusion of CMs could neutralize the acidity of PLA degradation products. Compared with the rapid release from CMs, the synthetic peptide was released from PLA/CMs scaffolds in a temporally controlled manner, mainly depending on the degradation of PLA matrix. The promising microspheres based scaffold release system can be used to deliver bioactive factors for a variety of non-loaded bone regeneration and tissue engineering application.     

Enzymatic and anaerobic degradation of amylose based acrylic copolymers, for use as matrices for drug release

The aim of this investigation is the use of starch for effective colon-targeted drug delivery. To this end, high-amylose starch-based copolymers were tested as matrices for drug delivery. Ethyl methacrylate (EMA) was grafted onto a high-amylose starch (A). Copolymer synthesis and characterization as well as other experiments to test the enzymatic resistance and the capacity for fermentation of these products by colonic bacteria were carried out. Finally, tablets developed with our copolymers were tested to observe the dissolution behaviour of a model drug and a model protein. Our findings indicate that large quantities of grafted PEMA are not necessary to obtain high enzymatic resistance. Fermentation experiments indicate that the carbohydrate of A-EMA copolymers is susceptible to fermentation in spite of the EMA coating around the amylose backbone and that these materials could favour colon-targeted delivery.     

Fabrication of ultrathin polyelectrolyte fibers and their controlled release properties

Ultrathin fibers comprising 2-weak polyelectrolytes, poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH) were fabricated using the electrospinning technique. Methylene blue (MB) was used as a model drug to evaluate the potential application of the fibers for drug delivery. The release of MB was controlled in a nonbuffered medium by changing the pH of the solution. The sustained release of MB in a phosphate buffered saline (PBS) solution was achieved by constructing perfluorosilane networks on the fiber surfaces as capping layers. Temperature controlled release of MB was obtained by depositing temperature sensitive PAA/poly(N-isopropylacrylamide) (PNIPAAM) multilayers onto the fiber surfaces. The controlled release of drugs from electrospun fibers have potential applications as drug carriers in biomedical science.     

Characterization and in vitro release kinetics of chitosan based biocomposites from Scotch Bonnets

The main aim of this study is to formulate the combination of the bioactive composite containing chitosan/β -tricalcium phosphate (CH/β-TCP) as potential drug delivery platforms for the sustained release of antibiotics. Herein the mode of amoxicillin (AMX) maintained in the β-TCP/chitosan composite was characterized using XRD, FT-IR to confirm the phase purity and functional groups. SEM was used to examine the size and shape of particles. The SEM images of the biocomposites after drug release confirmed that they are biodegradable. In vitro drug release experiments in PBS (pH 7.4) revealed a sustained release profile in a neutral medium. Drug release profiles were evaluated according to five different kinetic models including Zero Order, First Order, Higuchi, Hixon Crowel, and Korsmeyer-Peppas. The release profile was best expressed by the Korsmeyer Peppas model because the results showed high linearity. Overall, the positive effect of chitosan coating on the drug elution profile of β-TCP as carriers for the controlled delivery of antibiotics was regarded as biocompatible for the controlled drug delivery system.     

In vitro release of incorporated model compounds in poly(sebacic anhydride-co-ethylene glycol)

Poly(sebacic anhydride-co-ethylene glycol) was synthesized by using sebacic anhydride prepolymer and poly(ethylene glycol) for encapsulation of p-nitroaniline and brilliant blue G as modeling drugs to investigate the behavior of hydrophobic and hydrophilic drug release, respectively. Since p-nitroaniline is likely located in the sebacic anhydride-rich phase and brilliant blue G in the PEG-rich phase, respectively, their incorporation would affect the phase behavior of the host polymer. Different pore structure of eroded polymer matrix and drug release behavior were identified for hydrophobic and hydrophilic compounds. With a certain amount of PEG in the copolymer matrix, low drug release rate was accomplished for hydrophobic drug incorporation.     

Hydrogel matrices containing single and mixed natural cyclodextrins. Mechanisms of drug release

Hydrogel networks of α, β or γ-cyclodextrin (CD) and mixtures of α/β or β/γ CDs have been obtained using epichlorohydrin (EP) as a crosslinking agent. Discs of the resulting polymers were evaluated as drug carriers for controlled release using the antiinflammatory naproxen (NAP) as a model drug. βCD polymer (βCDP) has shown the highest amount of drug loaded and the lowest one corresponds to the polymer containing αCD, in agreement with the affinities of NAP for the corresponding cyclodextrins.     

Multilayered electrospun nanofibrous scaffolds for tailored controlled release of embelin

Polymeric electrospun meshes are highly attractive as versatile platforms for numerous biomedical applications, tissue engineering, biosensors, and controlled release of bioactive agents. Herein, we describe the preparation and characterization of multilayered nanofibrous poly(ε-caprolactone) scaffolds with different embelin content by electrospinning technique. In vitro release in physiological and acidic pH and kinetic analysis were performed. The results show that it is possible to modulate the release profile depending on the number and thickness of layers added to drug-loaded scaffold that acts as an embelin reservoir. Electrospun multilayered scaffolds present characteristics, morphology and release profiles that could be very attractive for use as embelin controlled release systems.     

Influence of speciation in the release profiles and antimicrobial performance of electrospun ethylene vinyl alcohol copolymer (EVOH) fibers containing ionic silver ions and silver nanoparticles

In the present study, tailor-made ethylene vinyl alcohol copolymer (EVOH) fibers containing different amounts of antimicrobial silver ions and nanoparticles were developed by electrospinning and subsequent thermal annealing. The morphology of the fibers was examined by scanning and transmission electron microscopy and thermal properties were characterized by differential scanning calorimetry. Speciation and controlled release of silver from the fibers was monitored by anodic stripping voltammetry and energy dispersive X-ray spectroscopy. Before aging, 100 % of the silver recovered from the electrospun structures was in ionic form to be instantly released in contact with moisture with varying temperature-dependent kinetics. Thermal annealing of the fibers at 100 °C for 1, 2, and 4 days prompted the gradual transformation of 70, 93–94, and 98–99 % of the total silver into nanoparticles homogeneously distributed along the fibers, which were mostly retained within them, producing a substantial decrease in their release capacity. Speciation and release profiles from the fibers were correlated with their antibacterial performance against Listeria monocytogenes and Salmonella enteric. This study is a step forward in the understanding of silver-based electrospun antimicrobial polymers and puts forth the suitability of EVOH for the development of targeted delivery systems in a number of applications.     

Functionalized mesoporous materials for adsorption and release of different drug molecules: A comparative study

The adsorption capacity and release properties of mesoporous materials for drug molecules can be improved by functionalizing their surfaces with judiciously chosen organic groups. Functionalized ordered mesoporous materials containing various types of organic groups via a co-condensation synthetic method from 15% organosilane and by post-grafting organosilanes onto a pre-made mesoporous silica were synthesized. Comparative studies of their adsorption and release properties for various model drug molecules were then conducted. Functional groups including 3-aminopropyl, 3-mercaptopropyl, vinyl, and secondary amine groups were used to functionalize the mesoporous materials while rhodamine 6G and ibuprofen were utilized to investigate the materials’ relative adsorption and release properties. The self-assembly of the mesoporous materials was carried out in the presence of cetyltrimethylammonium bromide (CTAB) surfactant, which produced MCM-41 type materials with pore diameters of ∼2.7-3.3 nm and moderate to high surface areas up to ∼1000 m²/g. The different functional groups introduced into the materials dictated their adsorption capacity and release properties. While mercaptopropyl and vinyl functionalized samples showed high adsorption capacity for rhodamine 6G, amine functionalized samples exhibited higher adsorption capacity for ibuprofen. While the diffusional release of ibuprofen was fitted on the Fickian diffusion model, the release of rhodamine 6G followed Super Case-II transport model.     

In vitro and in vivo evaluation of silk fibroin-hardystonite-gentamicin nanofibrous scaffold for tissue engineering applications

Designing advanced biomaterials with regenerative and drug delivering functionalities remains a challenge in the field of tissue engineering. In this paper we present the design, development, and a use case of an electrospun nano-biocomposite scaffold composed of silk fibroin (SF), hardystonite (HT), and gentamicin (GEN). The fabricated SF nanofiber scaffolds provide mechanical support while HT acts as a bioactive and drug carrier, on which GEN is loaded as an antibacterial agent. Antibacterial zone of inhibition (ZOI) results indicate that the inclusion of 3–6 wt% GEN significantly improves the antibacterial performance of the scaffolds against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, with an initial burst release of 10–20% and 72–85% total release over 7 days. The release rate of stimulatory silicon ions from SF-HT scaffolds reached 94.53±5 ppm after 7 days. Cell studies using osteoblasts show that the addition of HT significantly improved the cytocompatibility of the scaffolds. Angiogenesis, in vivo biocompatibility, tissue vascularization, and translatability of the scaffolds were studied via subcutaneous implantation in a rodent model over 4-weeks. When implanted subcutaneously, the GEN-loaded scaffold promoted angiogenesis and collagen formation, which suggests that the scaffold may be highly beneficial for further bone tissue engineering applications.     

Polylactic acid/polypropylene polyblend fibers for better resistance to degradation

Polyblend fibers were produced from five ratios of polylactic acid/polypropylene (PLA/PP) in an effort to improve the resistance to hydrolysis and biodegradation, and to improve the dyeability of PLA. The inherent limitations of PLA such as its relatively poor resistance to hydrolysis have restricted the use of PLA. When made into polyblend fibers, the two polymers, PLA and PP, show partial compatibility and the mechanical properties of the blends are inferior compared to the pure PLA or PP fibers. However, PLA in the blends had substantially better resistance to biodegradation and hydrolysis, and dyeability with disperse dyes, resulting in a polyblend fiber with much better resistance to hydrolysis and similar dyeability to PLA. Blending PP with PLA could be a simple and effective method to create a new fiber with better resistance to hydrolysis and lower price than PLA, and better dyeability, sustainability and faster degradability than PP.     

Preparation of chitosan scaffolds loaded with dexamethasone for tissue engineering applications using supercritical fluid technology

Supercritical fluid impregnation was tested to prepare a new scaffold loaded with a bioactive compound. Dexamethasone is used in osteogenic media to direct the differentiation of stem cells towards the osteogenic lineage. Dexamethasone was impregnated in chitosan scaffolds at different operating conditions, in order to optimize the impregnation process. Pressure and temperature affect the carbon dioxide density and influence the swelling of the polymer and the drug solubility in the fluid phase, therefore these are two important parameters that were studied in this work. Chitosan sponges prepared by freeze drying were impregnated with the active compound at pressures from 8.0 up to 14.0 MPa and temperatures from 35 up to 55 °C. The effect of the impregnation contact time (3 h and 6 h) was also evaluated. From the experiments performed we can conclude that the yield of impregnation is lower when increasing pressure and temperature. The contact time will mainly influence the amount of drug impregnated in the scaffold and for higher contact times the impregnation yield is also higher. Scanning electron microscopy shows particles of dexamethasone in the bulk of the scaffold, which confirms the feasibility of the supercritical fluid impregnation technology for the preparation of delivery devices. The loading capacity of the scaffolds was determined by spectroscopic analysis and the highest loading was achieved for the experiments performed at 8.0 MPa and 35 °C. Furthermore, in vitro drug release studies were carried out and the results show that dexamethasone was sustainably released. Supercritical fluid impregnation proved to be feasible for the preparation of a drug delivery system for bone tissue engineering purposes.     

In vitro degradation characteristics of poly(anhydride-imides) containing pyromellitylimidoalanine

The in vitro degradation characteristics of poly(anhydride-imides) containing pyromellitylimidoalanine, with either 1,6-bis(carboxyphenoxy)hexane (CPH) or sebacic acid (SA) were assessed. The copolymers contained up to 50 mol % of the imide monomer, pyromellitylimidoalanine (PMA-ala). Degradation was pH sensitive, being enhanced under basic conditions. Control of degradation times from 2 days to 2 months was achieved by the selection of appropriate monomer units in the polymer backbone. Monomers were chosen based on their solubility in aqueous media, as well as how they influenced the hydrophobicity and crystallinity of the polymer matrices. Polymer degradation was followed by ultraviolet spectroscopy and high-pressure liquid chromatography. Increasing the amount of imide monomer, PMA-ala, and the use of SA (rather than CPH) as the comonomer increased the degradation rate of the polymer matrices. © 1996 John Wiley & Sons, Inc.     

Structural changes of biocompatible neutral microemulsions stabilized by mixed surfactant containing soya phosphatidylcholine and their relationship with doxorubicin release

Depending on the composition, the mixture of surfactant, oil and water, may form supramolecular aggregates with different structures which can significantly influence the drug release. In this work several microemulsion (ME) systems containing soya phosphatidylcholine (SPC) and eumulgin HRE40™ (EU) as surfactant, cholesterol (O) as oil phase, and ultra-pure water as an aqueous phase were studied. MEs with and without the antitumoral drug doxorubicin (DOX) were prepared. The microstructures of the systems were characterized by photon correlation spectroscopy, rheological behavior, polarized light microscopy, small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD). The results reveal that the diameter of the oil droplets was dependent on the surfactant (S) amount added to formulations. The apparent viscosity was dependent on the O/S ratio. High O/S ratio leads to the crystallization of cholesterol polymorphs phases which restricts the mobility of the DOX molecules into the ME structure. Droplets with short-range spatial correlation were formed from the ME with the low O/S ratio. The increase of the cholesterol fraction in the O/S mixture leads to the formation of ordered structures with lamellar arrangements. These different structural organizations directly influenced the drug release profiles. The in vitro release assay showed that the increase of the O/S ratio in the formulations inhibited the constant rate of DOX release. Since the DOX release ratio was directly dependent on the ratio of O/S following an exponential decay profile, this feature can be used to control the DOX release from the ME formulations.     

天然多糖类纳米凝胶药物载体的研究进展

天然多糖具有来源广泛、价格低廉、良好的生物相容性和生物可降解性等特点,被广泛应用于药物载体研究。天然多糖纳米凝胶内部交联网络结构能有效提高药物的稳定性,且自身带有大量的活性官能团,可以被修饰上靶向配体或者对病灶环境敏感的基团,使药物顺利到达靶向细胞,从而实现药物的可控释放,在提高药效的同时降低药物的毒副作用。该综述介绍了天然多糖类纳米凝胶作为药物载体的研究进展,包括壳聚糖、右旋糖酐、普鲁兰多糖、海藻酸盐、透明质酸以及肝素等天然多糖纳米凝胶用于环境响应药物可控释放和靶向药物治疗的研究状况,并对其未来发展方向进行了展望。