Search

Objective: A saliva substitute based on polyglycerylmethacrylate, lactoperoxidase, and glucose oxidase (Oral Balance) has been developed. The aim of this study was to evaluate the effect of Oral Balance on the dryness-related oral complaints in patients suffering from irradiation-induced xerostomia. Method and materials: The efficacy of Oral Balance on the dryness-related complaints of 28 patients was assessed by means of self-administered questionnaires. Each patient completed an initial questionnaire about dryness-related symptoms and then was given the moistening gel. The patients were instructed to apply the gel as often as desired. After 2 weeks and 3 months, the patients were asked to complete a progress questionnaire. The severity of xerostomia was measured with a saliva absorption method. Results: All patients suffered from moderate-to-severe xerostomia, the severity of which did not change during the experimental period. Three patients did not complete the study. In the other 25 patients, the application of Oral Balance tended to diminish the sensation of oral dryness and improve oral functioning. Statistically significant reduction of the dryness-related complaints was observed only in the patients suffering from severe xerostomia. Conclusion: Use of Oral Balance is of potential benefit in patients suffering from severe xerostomia. [ABSTRACT FROM AUTHOR]

Since the early days of the Journal of Controlled Release , there has been considerable interest in materials that can release drug on an “on-demand” basis. So called “stimuli-responsive” and “intelligent” systems have been designed to deliver drug at various times or at various sites in the body, according to a stimulus that is either endogenous or externally applied. In the past three decades, research along these lines has taken numerous directions, and each new generation of investigators has discovered new physicochemical principles and chemical schemes by which the release properties of materials can be altered. No single review could possibly do justice to all of these approaches. In this article, some general observations are made, and a partial history of the field is presented. Both open loop and closed loop systems are discussed. Special emphasis is placed on stimuli-responsive hydrogels, and on systems that can respond repeatedly. It is argued that the most success at present and in the foreseeable future is with systems in which biosensing and actuation (i.e. drug delivery) are separated, with a human and/or cybernetic operator linking the two. [ABSTRACT FROM AUTHOR]

Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Biomedical application of hydrogels was initially hindered by the toxicity of crosslinking agents and limitations of hydrogel formation under physiological conditions. Emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. Hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical crosslinks. With their capacity to embed pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form promising materials for controlled drug release and tissue engineering. Despite all their beneficial properties, there are still several challenges to overcome for clinical translation. In this review, we provide a historical overview of the developments in hydrogel research from simple networks to smart materials. [ABSTRACT FROM AUTHOR]

Thermally induced gelling systems have gained enormous attention over the last decade. They consist of hydrophilic homopolymers or block copolymers in water that present a sol at room temperature and form a gel after administration into the body. This article reviews the main types of thermoresponsive polymers, with special focus on decisive hydrogel characteristics, mechanisms of gelation, and biocompatibility. Promising biomedical applications are described with a focus on injectable formulations, which include solubilization of small hydrophobic drugs, controlled release, delivery of labile biopharmaceutics, such as proteins and genes, cell encapsulation, and tissue regeneration. Furthermore, combinations of thermoresponsive hydrogels and various nanocarriers as promising systems for sustained drug delivery are discussed through selected examples from the literature. Finally, there is a brief overview of current progress in nano-sized systems incorporating thermoresponsive properties. [ABSTRACT FROM AUTHOR]

Temperature-sensitive hydrogels were designed using a series of A-B-A triblock copolymers consisting of poly (ethylene glycol) (PEG) with different molecular weights as the hydrophilic block B and poly (β-butyrolactone-co-lactic acid)(PBLA) with varying block lengths and composition as the hydrophobic block A. The triblock copolymers were synthesized by ring-opening polymerization (ROP) of β-BL and LA in bulk using PEG as an initiator and Sn(Oct)2 as the catalyst. Their chemical structure and molecular characteristics were determined by NMR, GPC and DSC, and the relationship between structure and phase behaviors in aqueous solutions was investigated as well. It was found that the phase behaviors in aqueous solutions including critical micelle concentration (CMC), sol-gel-sedimentation phase transition temperature, gel window width and critical gelation concentration (CGC) are largely dependent on the molecular weight and block length ratio of PEG/PBLA. Most importantly, they show a very low CGC ranging from 4 to 8 wt% because of the introduction of β-BL. Furthermore, the biodegradability and biocompatibility of the hydrogels were evaluated. Finally, lysozyme as a model protein was used to evaluate the ability to deliver protein drugs in a sustained release manner and biologically active form. All results demonstrated that the temperature-sensitive in situ forming hydrogel has a promising potential as sustained delivery system for protein drugs. [ABSTRACT FROM AUTHOR]

The reversible attachment of proteins to polymers is one potential strategy to control protein release from hydrogels. In this study, we report the reversible attachment of lysozyme to poly(ethylene glycol) (PEG) by degradable carbamate linkers. Phenyl groups with different substituents were used to control the rate of carbamate hydrolysis and the resulting protein release. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed modification with 1–3 PEG chains per lysozyme molecule. Protein PEGylation and PEG chain elimination occurred without changes in secondary protein structure, as demonstrated by circular dichroism spectroscopy. The lytic activity of lysozyme was restored to 73.4±1.7%–92.5±1.2% during PEG chain elimination. Attached PEG chains were eliminated within 24h to 28days, depending on the used linker molecule. When formulated into hydrogels, a maximum of about 60% of the initial dose was released within 7days to 21days. Linker elimination occurs ‘traceless’, so that the protein is released in its native, unmodified form. Altogether, we believe that tethering proteins by degradable carbamate linkers is a promising strategy to control their release from hydrogels. [ABSTRACT FROM AUTHOR]

Abstract: Multilayered polymer hydrogels containing living cells were assembled for assessing the distance-dependent effects of soluble factors secreted by stroma cells on tumor cell cycle progression in vitro. A layer of tumor cells and a layer of stroma cells were separated with finely controlled spacing in a multilayered sandwich composed of a 2-methacryloyloxyethyl phosphorylcholine polymer and poly(vinyl alcohol) hydrogel. We demonstrated the utility of this tool for investigating intercellular communication between human cervical cancer HeLa cells and supportive stromal L929 fibroblast cells in co-culture. Time-lapse microscopic analyses of HeLa cells showed short distances (15 μm) between tumor cells and stroma cells induced a continuous increase in the percentage of HeLa cells in the S/G2/M phases of the cell cycle, while longer distances (70 μm) between the cells caused a slower increase followed by a sharp increase in the percentage of cells in S/G2/M phases. One possible explanation is gradient formation in the diffusion-dominant multilayer hydrogels by water-soluble factors such as those inducing growth, differentiation, and proliferation. This study provides insights into the potential effects of diffusion of soluble factors and related distance-dependent effects on cell behavior, which may contribute to the design of future co-culture systems. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to explore a composite thermosensitive in situ gelling formulation using the distribution of solid lipid nanoparticles (SLNs) among poloxamer-based hydrogels as a potential carrier for novel ocular drug delivery. SLNs containing the model drug Resina Draconis were prepared using a melt-emulsion ultrasonication method. A central composite design (CCD) was adopted to screen the thermosensitive hydrogel (THG) formulation. After aqueous SLNs were dispersed into the THG matrices, the physicochemical properties of the SLNs were characterized before and after their incorporation into hydrogels. The in vitro corneal penetration experiment, ocular irritant test and transcorneal mechanism across the cornea have been previously described to predict the feasibility for the proposed ophthalmic application. Finally, the optimal THGs consisted of 27.8% (w/v) poloxamer 407 and 3.55% (w/v) poloxamer 188. The particle size of the SLNs remained within the colloidal range. In vitro corneal penetration studies revealed a nearly steady sustained drug release. The hen's egg test-chorioallantoic membrane (HET-CAM) test indicated that all of the tested polymer systems were non-irritant. Coumarin-6 labeled SLNs formulated into THGs displayed a more homogeneous fluorescence with a deeper penetration intensity into the cornea at various times. Taken together, these results suggest that the SLN-based THG system can be used as a potential vehicle for ocular application. [Copyright &y& Elsevier]

Abstract: Poly(N-acryloyl glycinamide) is a neutral polymer that can form gel–sol thermoresponsive systems with upper critical solution temperature in aqueous media. The temperature of the reversible gel–sol transition depends on the molar mass and the concentration of macromolecules. These parameters were combined to adjust the transition temperature slightly above body temperature for the sake of respecting living tissues during the sol form injection using a classical syringe. On contact with local tissues, the injected sol turned rapidly to a gel. The simplicity of the process makes it exploitable to administrate and deliver neutral or ionic drug and especially those that are soluble in aqueous media. The versatility was exemplified from formulations with cobalt acetate, small polymers (MW~2000g/mol), tartrazine and methylene blue dyes and albumin. The model compounds were allowed to diffuse in an isotonic pH=7.4 buffered medium at 37°C. All the release profiles were typical of diffusion control with 100% release within 2 to 3weeks and no obvious burst. The in vitro release of methylene blue from a gel formulation was checked prior to injection in the peritoneal cavity of mice where the release of the dye was monitored visually through tissue and organ colorations. A comparable polymer-free dye solution was used as control. Coloration appeared rapidly in tissues and organs and it was still detectable 52h post injection of the gel whereas it was no longer present at 24h in control mice. [Copyright &y& Elsevier]

Abstract: Temperature has been extensively explored as a trigger to control the delivery of a payload from environment-sensitive polymers. The need for an external heat source only allows limited spatiotemporal control over the delivery process. We propose a new approach by using the dissipative properties of a hydrogel matrix as an internal heat source when the material is mechanically loaded. The system is comprised of a highly dissipative hydrogel matrix and thermo-sensitive nanoparticles that shrink upon an increase in temperature. Exposing the hydrogel to a cyclic mechanical loading for a period of 5 min leads to an increase of temperature of the nanoparticles. The concomitant decrease in the volume of the nanoparticles increases the permeability of the hydrogel network facilitating the release of its payload. As a proof-of-concept, we showed that the payload of the hydrogel is released after 5–8 min following the initiation of the mechanical loading. This delivery method would be particularly suited for the release of growth factor as it has been shown that cell receptor to growth factor is activated 5–20 min following a mechanical loading. [Copyright &y& Elsevier]

Abstract: Non-viral gene delivery holds great promise for promoting tissue regeneration, and offers a potentially safer alternative than viral vectors. Great progress has been made to develop biodegradable polymeric vectors for non-viral gene delivery in 2D culture, which generally involves isolating and modifying cells in vitro, followed by subsequent transplantation in vivo. Scaffold-mediated gene delivery may eliminate the need for the multiple-step process in vitro, and allows sustained release of nucleic acids in situ. Hydrogels are widely used tissue engineering scaffolds given their tissue-like water content, injectability and tunable biochemical and biophysical properties. However, previous attempts on developing hydrogel-mediated non-viral gene delivery have generally resulted in low levels of transgene expression inside 3D hydrogels, and increasing hydrogel stiffness further decreased such transfection efficiency. Here we report the development of biodegradable polymeric vectors that led to efficient gene delivery inside poly(ethylene glycol) (PEG)-based hydrogels with tunable matrix stiffness. Photocrosslinkable gelatin was maintained constant in the hydrogel network to allow cell adhesion. We identified a lead biodegradable polymeric vector, E6, which resulted in increased polyplex stability, DNA protection and achieved sustained high levels of transgene expression inside 3D PEG-DMA hydrogels for at least 12 days. Furthermore, we demonstrated that E6-based polyplexes allowed efficient gene delivery inside hydrogels with tunable stiffness ranging from 2 to 175 kPa, with the peak transfection efficiency observed in hydrogels with intermediate stiffness (28 kPa). The reported hydrogel-mediated gene delivery platform using biodegradable polyplexes may serve as a local depot for sustained transgene expression in situ to enhance tissue engineering across broad tissue types. [Copyright &y& Elsevier]

Background: Hydrogels are widely used for cutaneous formulations; thereby comparing the bioadhesive properties of polymers with a view to prolong the residence time of topical drugs on the skin would be very useful to design novel topical drug delivery systems. Aim: The objective of this study was to correlate data from rheological studies and texture profile analysis, with bioadhesion on the skin. Methods: Polyacrylic acid polymers used were carbomer homopolymer type A (C971) and type B (C974), and polycarbophil (PP) dispersed in water at various concentrations (0.1, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0%, w/v). Rheological, texture, and bioadhesive properties were determined to compare the hydrogels. Results: Rheological analysis showed that all samples exhibited pseudoplastic behavior with thixotropy. Texture profile analysis showed that compressibility, hardness, and adhesiveness of the hydrogels were dependent on the polymer concentration, and the cohesion values were high. Bioadhesion of C974 and PP at 0.5 and 2% was of the same magnitude, while all samples of C971 had lower values. The bioadhesion of 5% C974 was the highest, while that 5% PP was lower, possibly because PP showed the greatest hardness and this rigidity may decrease the interaction of the polymer with the skin. Conclusion: A comprehensive comparative rheological and textural analyses of several polymers for topical systems were undertaken in terms of their bioadhesion. Therefore, it is possible to conclude that these polymers can be used for optimization of drug delivery systems on the skin. [ABSTRACT FROM AUTHOR]

In vitro and in vivo experimentation of various synthetic polymer hydrogels was conducted to establish some of the integral material properties that influence hemostasis. In vitro swelling experiments suggested that positive electrostatic charge was a key determinant of the ability of a polymer hydrogel to absorb physiological fluids, e.g. human plasma and blood. In vitro testing using unadulterated sheep blood suggested positive electrostatic charge and crosslink density were key determinants of the ability of a material to induce or enhance clot formation. Hydrogel formulations composed of higher amounts of positive electrostatic charge and lower crosslink density were able to effectively induce and enhance clot formation in the presence of a coagulation cascade activator. In vivo experimentation confirmed that hydrogels containing higher electrostatic charge and low crosslink density are more effective at fostering the formation of a robust hemostatic plug to control blood loss. [ABSTRACT FROM AUTHOR]

Silk-elastinlike protein polymers(SELPs) are recombinantpolymersconsisting of tandem repeats of silk (GAGAGS) and elastin (GVGVP)units. By modification of the length and composition of these repeats,the properties of SELP hydrogels can be controlled for specific applicationsincluding nucleic acid and virus delivery and tissue engineering.Here, the structure of SELPs is further modified to include a sequencethatis sensitive to matrix-metalloproteinases (MMPs). MMPs are a ubiquitousfamily of extracellular matrix-modifying enzymes that are commonlyassociated with numerous vital processes. Increased levels of MMPsare found at high levels locally in many types of solid tumors. Bymodifying the SELP backbone with MMP-sensitive peptide sequences,a hydrogel that is degradable by MMPs was produced. The MMP-sensitivityof the polymer was examined by incubation with MMP-2 and MMP-9, whichyielded complete cleavage of all full-length polymers by 36 hoursand 48 hours, respectively, with no observable effect on unmodifiedSELP. Hydrogel sensitivity was tested by exposure to MMP-2 or MMP-9for 2 weeks, during which samples were taken to analyze protein lossfrom the hydrogel and release of 100 nm fluorescent beads. Followingthe incubation period, hydrogels were tested in mechanical compressionto examine the loss of hydrogel stiffness due to degradation. It wasfound that MMP-2 and MMP-9 caused 63% and 44% increased protein lossand 65% and 95% increased release from MMP-sensitive hydrogels, whilethe compressive modulus decreased by 41% and 29%. These results suggestthe potential of MMP-responsive SELPs for localized delivery of bioactiveagents where MMPs are overexpressed. [ABSTRACT FROM AUTHOR]

When grafted β-cyclodextrin is used as targetingsites, Pluronicpolymers have been introduced on the surface of cellulose nanocrystalsby means of inclusion interaction between β-cyclodextrin andhydrophobic segment of the polymer. Because of the steric stabilizationeffect, surface poly(ethylene glycol) chains facilitate the dispersionand compatibility of nanocrystals, which also enhance the loadinglevels of nanocrystals in the hydrogel system. Meanwhile, uncoveredpoly(ethylene glycol) segments render the participating inclusionof α-cyclodextrin for the architecture of in situ hydrogels.Surface grafting and inclusion reactions were proved by solid 13C NMR and FTIR. Grafting efficiency of β-cyclodextrinand inclusion efficiency of Pluronic on the surface of nanocrystalswere confirmed by UV spectroscopy and elemental analysis. A significantenhancement of the structural and thermal stability of in situ hydrogelswith high loading levels of modified nanocrystals (>5.77 wt %)wasobserved by rheological analysis. Further study reveals the performanceand behavior of hydrogels under a different pH environment. Finally,in situ hydrogels were used as drug carrier for in vitro release ofdoxorubicin and exhibit the behavior of prolonged drug release withspecial release kinetics. [ABSTRACT FROM AUTHOR]

Pluronic® F127 is a biocompatible, injectable, and thermoresponsive polymer with promising biomedical applications. In this study, a chemically modified form, i.e., Pluronic ALA-L with tailored degradation rate, was tested as an encapsulation vehicle for osteoblastic cells. UV cross-linking of the modified polymer results in a stable hydrogel with a slower degradation rate. Toxicological screening showed no adverse effects of the modified Pluronic ALA-L on the cell viability. Moreover, high viability of embedded cells in the cross-linked Pluronic ALA-L was observed with life/death fluorescent staining during a 7-day-culture period. Cells were also cultured on macroporous, cross-linked gelatin microbeads, called CultiSpher-S® carriers, and encapsulated into the modified cross-linked hydrogel. Also, in this situation, good cell proliferation and migration could be observed in vitro. Preliminary in vivo tests have shown the formation of new bone starting from the injected pre-loaded CultiSpher-S® carriers. [ABSTRACT FROM AUTHOR]

Abstract: In the last past dozen years, polymersomes (Ps) have attracted tremendous attention as versatile carriers because of their colloidal stability, tunable membrane properties and ability in encapsulating or integrating a broad range of drugs and molecules. Relatively long blood circulation times of Ps can be accomplished when block copolymers with a poly(ethylene glycol) (PEG) are used for the formation of Ps. A number of Ps has been developed for new possibilities and applications in drug delivery, medical imaging, electronics and nanoreactors. In particular, Ps prepared by using biodegradable and/or stimuli-sensitive block copolymers that are responsive to various internal or external stimuli are of great interest for such applications. In this review, recent advances of Ps as drug delivery systems are discussed. Critical factors that influence the formation of Ps are also addressed. The review describes preparative methods and characterization techniques for Ps. Moreover, protein and cell interactions with Ps, in vivo circulation kinetics and biodistribution of Ps are addressed. [Copyright &y& Elsevier]

During the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug delivery. [ABSTRACT FROM AUTHOR]

Abstract: Numerous studies have addressed the controlled pulmonary drug delivery properties of colloidal particles. However, only scant information on the potential of spray-drying for submicron particle preparation is available. By exploiting the advantages of spray-drying, the characteristics of submicron particles can be optimized to meet the requirements necessary for lung application. Submicron particles were prepared from organic poly(d,l-lactide-co-glycolide) (PLGA) solutions, and composite particles were spray-dried from aqueous PLGA nanosuspensions. The feed concentration, as well as the spray-mesh diameter influenced the resulting particle sizes. Nanoparticles were virtually unaffected after spray-drying. The aerodynamic characteristics of both particle species revealed aerosol particle sizes suitable for deposition in the deep lungs (≤4μm). While the entrapped drug was released within ~90min from the composite particles, extensive drug retardation (~480min) was observed for PLGA particles spray-dried from organic solution. These results suggest that nanospray-drying is a convenient method to prepare submicron, controlled drug delivery vehicles useful for pulmonary application potentially allowing access to alveolar tissue. [Copyright &y& Elsevier]

This review highlights references where ethylcellulose, methylcellulose and hypromellose were used to make microcapsules. The review has been divided into three parts. This first part discusses various materials used to formulate microcapsules, such as the three encapsulating polymers as well as protective colloids, plasticizers and surfactants. The second part covers the various techniques used to make microcapsules, such as temperature-induced phase separation, emulsion solvent evaporation, solvent evaporation, film coating, and others. The third part covers the various applications for which microcapsules are used, such as modified release, improved efficacy and safety, taste- and odor-masking, and others. It is hoped that formulators can use Part 1 as a guide to the literature documenting formulation of microcapsules made from these encapsulating polymers. SciFinder was utilized to identify the pertinent literature. SciFinder leverages literature databases, such as Chemical Abstracts Service Registry and Medline. A total of 379 references were identified during the review. The need for a three-part review reflects the extensive amount of literature identified concerning these three encapsulating polymers. [ABSTRACT FROM AUTHOR]

Abstract: Hexanediol diacrylate cross-linked oligoethylenimine (OEI-HD) is a non-viral polymeric vector designed to deliver siRNA. To achieve safe and effective in vivo siRNA delivery using this vector, the polyplex must have sufficient colloidal stability if administered intravenously or nebulized for delivery by the pulmonary route. In this study, polyplexes from OEI-HD and siRNA were formulated for aerosol-based lung delivery, regarding their colloidal stability, optimal particle size, and in vitro biological activity. Herein, we describe how these properties are dependent upon the polymer-to siRNA weight ratios, buffer composition they were complexed in, PEG-grafting, and the addition of commercial lung surfactants and/or non-ionic surfactants to the formulation. Lastly, the effects of nebulization of the formulation into aerosol droplets, on the polyplex particle size and transfection efficiency, were evaluated. Polyplex size was monitored for up to 2h after polyplex formation to determine the extent of aggregation and final particle sizes when stability was achieved. Our results suggest that PEG-grafting and polyethylenimine-PEG mixing were effective in achieving colloidal stability in isotonic saline buffers. In addition, colloidal stability was achieved in isotonic glucose buffers using commercially available non-ionic surfactant Pluronic™ P68 or the lung-derived surfactant Alveofact™. The smallest particle size, 140nm, was obtained with Pluronic™ F68. For transfection efficiency, both Alveofact™ and Pluronic™ F68 achieved equal or better transfection when added to the OEI-HD/siRNA polyplexes. For long term storage of OEI-HD/siRNA formulations, we propose a lyophilization method that created in situ polyplexes upon addition of water. Preparation of OEI-HD/siRNA polyplexes by this method allowed dry storage at room temperature for up to the 3months. In conclusion, we have identified approaches to achieve formulation and colloidal stability of OEI-HD/siRNA complexes, a step toward successful application of polyplexes for in vivo siRNA delivery. [Copyright &y& Elsevier]

Abstract: We have developed a synthetic polymer interface for the long-term self-renewal of human embryonic stem cells (hESCs) in defined media. We successfully cultured hESCs on hydrogel interfaces of aminopropylmethacrylamide (APMAAm) for over 20 passages in chemically-defined mTeSR™1 media and demonstrated pluripotency of multiple hESC lines with immunostaining and quantitative RT-PCR studies. Results for hESC proliferation and pluripotency markers were both qualitatively and quantitatively similar to cells cultured on Matrigel™-coated substrates. Mechanistically, it was resolved that bovine serum albumin (BSA) in the mTeSR™1 media was critical for cell adhesion on APMAAm hydrogel interfaces. This study uniquely identified a robust long-term culture surface for the self-renewal of hESCs without the use of biologic coatings (e.g., peptides, proteins, or Matrigel™) in completely chemically-defined media that employed practical culturing techniques amenable to clinical-scale cell expansion. [Copyright &y& Elsevier]

Abstract: The mechanical stiffness of a hydrogel plays a significant role in regulating the phenotype of cells that adhere to its surface. However, the effect of hydrogel stiffness on cells cultured within its matrix is not well understood, because of the intrinsic inverse dependency between the permeability and stiffness of hydrogels. This study therefore presents an advanced biomaterial design strategy to decrease the inverse dependency between permeability and stiffness of a cell encapsulating hydrogel. Hydrogels were made by cross-linking poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) monoacrylate (PEGMA), with PEGMA acting as a pendant polymer chain. Increasing the mass fraction of PEGMA while keeping the total polymer concentration constant led to a decrease in the elastic modulus (E) of the hydrogel, but caused a minimal increase in the swelling ratio (Q). The size and hydrophobicity of the end groups of pendant PEG chains further fine tuned the dependency between Q and E of the hydrogel. Pure PEGDA hydrogels with varying molecular weights, which show the same range of E but a much greater range of Q, were used as a control. Fibroblasts encapsulated in PEGDA–PEGMA hydrogels displayed more significant biphasic dependencies of cell viability and vascular endothelial growth factor (VEGF) expression on E than those encapsulated in pure PEGDA hydrogels, which were greatly influenced by Q. Overall, the hydrogel design strategy presented in this study will be highly useful to better regulate the phenotype and ultimately improve the therapeutic efficacy of a wide array of cells used in various biology studies and clinical settings. [Copyright &y& Elsevier]

Abstract: Silicone gel-like polymers have been proposed to replace the cataractous lens and therewith restore both vision and accommodation. Lens replacement is associated with opacification of the capsular bag due to the lens epithelial cell response. In this study, the in vivo effectiveness of a 5 min treatment with actinomycin D and/or cycloheximid to prevent the development of capsular opacification after filling the capsular bag with a silicone polymer as an accommodating lens was studied. It was found that treating the inside of the capsular bag with a solution containing actinomycin D reduced the development of visible capsular opacification for three months. In some animals, the lens capsules were completely clear, indicating the potential of this method. Side effects of the treatment in the form of visible cornea opacification occurred and ranged from mild to severe in some animals, while in other animals no toxicity occurred. This indicates that a safe application of the cytotoxic substances is feasible. In view of the side effects and the fact that not all lens capsules of the animals treated with actinomycin D were clear, improvements in the methods used are necessary and seem to be possible. [Copyright &y& Elsevier]

Purpose: A challenge in the field of nanobubbles, including lipobubbles and polymeric nanobubbles, is identification of formulation approaches to enhance circulation time or 'bubble life' in the specific organ to allow for organ visualization. The aim of this study was to investigate the potential of two specific preparation approaches, polymeric surface modification to lipobubbles and a one-step approach for the preparation of ionotropically originated polymeric hydrogel nanobubbles for the production of biocompatible, biodegradable, and sufficiently echogenic ('flexible') bubbles, preferably within the nanometer range, that possess an enhanced in vivo lifetime compared to an unmodified lipobubble to allow visualization of the lymph node vasculature. Methods: In the first approach, formed liposomes (basic and polymerically enhanced) were sequentially layered with appropriate cationic and anionic polyelectrolytes followed by transformation into polymer-coated nanobubbles. In addition, a one-step approach was employed for the fabrication of ionotropically originated polymeric hydrogel bubbles. Results: Bubble lifetime was marginally enhanced by self-deposition of polyelectrolytes onto the normal lipobubble, however, not significantly ( P = 0.0634). In general, formulations possessing a higher ratio of anionic:cationic coats and highly anionic overall surface charge (−20.62 mV to −17.54 mV) possessed an enhanced lifetime. The improvement in bubble lifetime was significant when a purely polymeric polyionic hydrogel bubble shell was instituted compared to a normal unmodified lipobubble ( P = 0.004). There was enhanced persistence of these systems compared to lipobubbles, attributed to the highly flexible, interconnected hydrogel shell which minimized gas leakage. The prolonged contrast signal may also be attributed to a degree of polymeric deposition/endothelial attachment. Conclusions: This study identified the relevance of polymeric modifications to nanobubbles for an improved circulating lifetime, which would be essential for application of these systems in passive drug or gene targeting via the enhanced permeability and retention effect. [ABSTRACT FROM AUTHOR]

The formation of microspheres from various pectin hydrogel complexes and corn zein in the presence of calcium and zinc ions has been studied. It is shown that the formation of microspheres and their loading capacity for a drug (piroxicam) depend on the type of biopolymers, their ratio, the sizes of the bivalent ions, and the molecular mass of the pectin. Complex formation between the two biopolymers results predominantly from bivalent metal cross-linking for low-methylated pectins and from hydrophobic interaction for high-methylated pectins. As a result, a series of microspheres have been prepared from biodegradable and biocompatible polymers and may find application as controlled-release drug delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: A novel polysaccharide derivative with photoreactivity was prepared by the conjugation of carboxymethylated chitosan with N-hydroxyl succinimide-activated nitrocinnamate in the presence of N,N-dicyclohexylcarbodiimide, and characterized by IR, 1H NMR, UV–vis and rheological analyses. It was found that such a modified polysaccharide could exhibit an unique photogelation ability in the absence of potentially toxic photoinitiator or catalyst and be suitable particularly for the in situ preparation of photocrosslinked hydrogel biomaterials. By changing the photoirradiation time and incorporated nitrocinnamate content, its photogelation property could be modulated. For the resultant hydrogels incorporated with various nitrocinnamate contents, their properties such as swelling, viscoelasticity, in vitro biodegradation and drug release were investigated. In addition, the photogelation mechanism of this polysaccharide derivative was also discussed. [Copyright &y& Elsevier]

This review describes the synthesis, properties, and, in particular, biomedical and pharmaceutical applications of an upcoming class of polymeric networks and assemblies based on cyclodextrins (CDs). CDs are cyclic oligosaccharides composed of α-1,4-coupled d-glucose units, which contain a hydrophobic internal cavity that can act as a host for various, generally lipophilic, guest molecules. Because of this unique physicochemical property, commonly referred to as inclusion complex formation, CDs have often been used to design polymeric materials, such as hydrogels and nanoparticles. Polymeric systems based on CDs exhibit unique characteristics in terms of mechanical properties, stimuli-responsiveness, and drug release characteristics. In this contribution, first, an outline is given of covalently cross-linked polymeric networks in which CD moieties were structurally incorporated to modulate the network strength as well as the complexation and release of low molecular weight drugs. Second, physically assembled polymeric systems are discussed, of which the formation is accomplished by inclusion complexes between polymer-conjugated CDs and various guest molecule-derivatized polymers. Due to their physical nature, these polymeric systems are sensitive to external stimuli, such as temperature changes, shear forces and the presence of competing CD-binding molecules, which can be exploited to use these systems as injectable, in situ gelling devices. In recent years, many interesting CD-containing polymeric systems have been described in literature. These systems have to be optimized and extensively evaluated in preclinical studies concerning their safety and efficacy, making future clinical applications of these materials in the biomedical and pharmaceutical field feasible. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to prepare and cross-link carrageenan beads that may be used as a controlled release delivery system. The influence of the bulk carrageenan and cross-linker concentrations on the bead size was studied in order to assess the mechanism of cross-linking between epichlorohydrin and the polysaccharide. The conditions were optimised on macroparticles (3.1mm in diameter) for a better understanding of the cross-link density and its effect on the morphology and surface topography of the bead. It was shown that low epichlorohydrin concentrations led to unstable and weak beads with uneven and cracked surfaces. The optimum cross-linker concentration, which resulted in smooth and stable gel beads, was applied to microparticles (76μm in diameter). The swelling/shrinking behaviour of these cross-linked microgels in saline solutions showed great potential for the application of these micro-sponges as delivery systems in food or pharmaceutical products. [Copyright &y& Elsevier]

Abstract: Poly(ɛ-caprolactone)–poly(ethylene glycol) (PCL–PEG) copolymers are important synthetic biomedical materials with amphiphilicity, controlled biodegradability, and great biocompatibility. They have great potential application in the fields of nanotechnology, tissue engineering, pharmaceutics, and medicinal chemistry. This review introduced several aspects of PCL–PEG copolymers, including synthetic chemistry, PCL–PEG micro/nanoparticles, PCL–PEG hydrogels, and physicochemical and toxicological properties. [Copyright &y& Elsevier]

Abstract: This paper is aimed to the macro- and microscopic characterisation of a scleroglucan–borax gel system eventually hosting model drugs. A rheological study was carried out, also as a function of temperature, on samples at different polymer concentrations in the presence and without guest model drug. Applying the generalised Maxwell model the mechanical spectra, showing the gel-like characteristics dependent on polymer concentration, were obtained. Flory’s theory and the equivalent network approach were applied to the rheological data in order to describe the molecular arrangement of the scleroglucan chains in the presence of borate ions with an estimation of the network mesh size, ξ. Diffusion experiments of three model drugs, with different van der Waals radius, allowed the determination of the diffusion coefficients. An evaluation of the network mesh size was also obtained by means of a modified free volume theory and a good agreement between the two sets of ξ values was found. [Copyright &y& Elsevier]

Abstract: The work demonstrates the development of acid-labile temperature-responsive sol–gel reversible polymer for enhanced in vivo myocardium and skeletal muscle gene delivery. In this report, multi-block copolymers (MBCPs) synthesized from pluronic® and di-(ethylene glycol) divinyl ether (DEGDVE) were used as a delivery vehicle for controlled and sustained release of plasmid DNA (pDNA) in in vitro as well as in vivo experiments. The non-ionic MBCP/pDNA complex showed remarkable transfection efficiencies against the myocardium cells as well as muscle cells in vivo, which is otherwise very difficult to achieve by using cationic polymers. In in vitro experimental settings, this intelligent stimuli-responsive polymer is shown to improve the transfection efficiency of branched polyethylenimine (BPEI)/pDNA complex when used together. The effect of MBCP on the surface charge and particle size of its various complexes with pDNA and BPEI was also studied. The release profile of pDNA from the MBCP gel was investigated and pH of the degraded polymer was also monitored to ascertain its non-cytotoxicity arising due to the increased acidity as observed with other PLGA-based polymers. The rapid sol–gel transition of MBCP under thermal stimuli with concomitant release of pDNA under acidic stimulation has potential for site specific, efficient and controlled transfection of therapeutic gene. In short, MBCP provides the silver lining in combat against the hurdles encountered in transfection to myocardial or other muscle cells. [Copyright &y& Elsevier]

Abstract: Here we describe the functionalization of a multilayered hydrogel layer on a Ti alloy with an antineoplastic agent, paclitaxel (PTX). The multilayered hydrogel was synthesized via layer-by-layer self-assembly (LbL) using selective intermolecular reactions between two water-soluble polymers, phospholipid polymer (PMBV) containing a phenylboronic acid unit and poly(vinyl alcohol) (PVA). Reversible covalent bonding between phenylboronic acid and the polyol provided the driving force for self-assembly. Poorly water-soluble PTX dissolves in PMBV aqueous solutions because PMBV is amphiphilic. Therefore, our multilayered hydrogel could be loaded with PTX at different locations to control the release profile and act as a drug reservoir. The amount of PTX incorporated in the hydrogel samples increased with the number of layers but was not directly proportional to the number of layers. However, as the step for making layers was repeated, the concentration of PTX in the PMBV layers increased. The different solubilities of PTX in PMBV and PVA aqueous solutions allow for the production of multilayered hydrogels loaded with PTX at different locations. In vitro experiments demonstrated that the location of PTX in the multilayered hydrogel influences the start and profile of PTX release. We expect that this rapid and facile LbL synthesis of multilayered hydrogels and technique for in situ loading with PTX, where the location of loading controls the release pattern, will find applications in biomedicine and pharmaceutics as a promising new technique. [Copyright &y& Elsevier]

Abstract: We report on the use of degradable polymer capsules as carriers for the delivery of oligopeptide antigens to professional antigen presenting cells (APCs). To achieve encapsulation, oligopeptide sequences were covalently linked to a negatively charged carrier polymer via biodegradable linkages and the resulting conjugate was then adsorbed onto amine-functionalized silica particles. These peptide-coated particles were then used as templates for the layer-by-layer (LbL) deposition of thiolated poly(methacrylic acid) (PMASH) and poly(vinylpyrrolidone) (PVPON) multilayers. Removal of the silica core and disruption of the hydrogen bonding between PMASH and PVPON by altering the solution pH yielded disulfide-stabilized PMA capsules that retain the encapsulated cargo in an oxidative environment. In the presence of a natural reducing agent, glutathione, cleavage of the disulfide bonds causes release of the peptide from the capsules. The developed strategy provides control over peptide loading into polymer capsules and yields colloidally stable micron- and submicron-sized carriers with uniform size and peptide loading. The conjugation and encapsulation procedures were proven to be non-degrading to the peptide vaccines. The peptide-loaded capsules were successfully used to deliver their cargo to APCs and activate CD8 T lymphocytes in a non-human primate model of SIV infection ex vivo. The reported approach represents a novel paradigm in the delivery of peptide vaccines and other therapeutic agents. [Copyright &y& Elsevier]

Abstract: Local delivery of anti-tumor drugs provides a high local concentration and decreases the incidence of side effects commonly observed with systemic therapy. Hydrogel systems are commonly used as a local drug delivery system. In this study, we prepared a novel thermosensitive conjugated linoleic acid (CLA)-coupled poloxamer hydrogel for local delivery of paclitaxel (PTX) to gain the benefits of the pro-drug activity of the CLA-coupled poloxamer and enhanced PTX solubility due to the micellar property of the CLA-coupled poloxamer. To evaluate the anti-tumor activity of the PTX-incorporated CLA-coupled poloxamer hydrogel in vivo, formulations were injected subcutaneously into tumor-bearing mice. Cell cycle and apoptosis markers were examined to determine the mechanism of the anti-tumor activity of PTX. The PTX-incorporated CLA-coupled poloxamer thermosensitive hydrogel showed excellent anti-tumor activity in vivo inducing stronger cell cycle arrest and apoptosis in tumor tissue than the PTX-incorporated poloxamer hydrogel. These results were attributed to the synergistic effect of the anti-tumor property of PTX with released CLA from the CLA-coupled poloxamer as the pro-drug and the enhanced solubility of PTX resulting from the micellar property of the CLA-coupled poloxamer. The CLA-coupled poloxamer designed in this study has great potential as an effective injectable carrier of PTX. [Copyright &y& Elsevier]

Abstract: Modifications of poly(2-hydroxyethyl methacrylate) (PHEMA) with cholesterol and laminin have been developed to design scaffolds that promote cell–surface interaction. Cholesterol-modified superporous PHEMA scaffolds have been prepared by the bulk radical copolymerization of 2-hydroxyethyl methacrylate (HEMA), cholesterol methacrylate (CHLMA) and the cross-linking agent ethylene dimethacrylate (EDMA) in the presence of ammonium oxalate crystals to introduce interconnected superpores in the matrix. With the aim of immobilizing laminin (LN), carboxyl groups were also introduced to the scaffold by the copolymerization of the above monomers with 2-[(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA). Subsequently, the MCMEMA moiety in the resulting hydrogel was hydrolyzed to [2-(methacryloyloxy)ethoxy]acetic acid (MOEAA), and laminin was immobilized via carbodiimide and N-hydroxysulfosuccinimide chemistry. The attachment, viability and morphology of mesenchymal stem cells (MSCs) were evaluated on both nonporous and superporous laminin-modified as well as laminin-unmodified PHEMA and poly(2-hydroxyethyl methacrylate-co-cholesterol methacrylate) P(HEMA–CHLMA) hydrogels. Neat PHEMA and laminin-modified PHEMA (LN–PHEMA) scaffolds facilitated MSC attachment, but did not support cell spreading and proliferation; the viability of the attached cells decreased with time of cultivation. In contrast, MSCs spread and proliferated on P(HEMA–CHLMA) and LN-P(HEMA–CHLMA) hydrogels. [Copyright &y& Elsevier]

Abstract: In this paper, we reported the synthesis and properties of interpenetrating polymer network (IPN) hydrogel systems designed for colon targeted drug delivery. The gels were composed of konjac glucomannan (KGM) and cross-linked poly(acrylic acid) (PAA) by N,N-methylene-bis-(acrylamide) (MBAAm). It was possible to modulate the swelling degree of the gels. And the swelling ratio has sensitive respondence to the environmental pH value variation. The degradation tests show that the hydrogels retain the enzymatic degradation character of KGM. In vitro release of model drug VB12 was studied in the presence of Cellulase E0240 in pH 7.4 phosphate buffer at 37°C. The accumulative release percent of the model drug reached 85.6% after 48h and the drug release was controlled by the swelling and the degradation of the hydrogels. The results indicated that the IPN hydrogels can be exploited as potential carriers for colon-specific drug delivery. [Copyright &y& Elsevier]

Abstract Purpose  To develop paclitaxel-delivering PLGA microspheres entrapped in a gel matrix with sustained drug release properties and implantability advantages for local glioma chemotherapy. Methods  Paclitaxel-loaded PLGA microspheres were fabricated using electrohydrodynamic atomization and entrapped by electrospray and gelation. The physicochemical characterizations were performed using scanning electron microscopy and differential scanning calorimetry. The influence of various parameters on the disintegration time was investigated. In vitro release of paclitaxel was quantified using high performance liquid chromatography. Cytotoxicity of the formulations was assessed by the quantification of IC50 and caspase-3 activity against C6 glioma cells in vitro. The formulations were tested against a subcutaneous C6 glioma tumour in mice. Results  Highly monodisperse gel beads containing a uniform microsphere distribution were obtained. Gelation using Ca2 ions ensured entrapment of microspheres with high loading efficiency. With an increase in the gelation time, gelling bath concentration and decrease in microsphere loading, it was more difficult to disintegrate the beads and release the microspheres. The formulations demonstrated sustained drug release for more than 60 days at a near-constant rate and a low initial burst. Cell culture studies proved the cytotoxicity against C6 glioma and improved performance in comparison to Taxol®. The formulations could reduce subcutaneous tumour volume to a greater extent compared to Taxol® and the control. Conclusions  Paclitaxel-loaded PLGA microspheres entrapped in an alginate gel matrix could be potential local chemotherapy implants to treat malignant glioma with critical advantages of implantability and sustained drug release with low initial burst. [ABSTRACT FROM AUTHOR]

Abstract: To engineer complex tissues, it is necessary to create hybrid scaffolds with micropatterned structural and biomechanical properties, which can closely mimic the intricate body tissues. The current report describes the synthesis of a novel photocrosslinkable interpenetrating polymeric network (IPN) of collagen and hyaluronic acid (HA) with precisely controlled structural and biomechanical properties. Both collagen and HA are present in crosslinked form in IPNs, and the two networks are entangled with each other. IPNs were also compared with semi-IPNs (SIPN), in which only collagen was in network form and HA chains were entangled in the collagen network without being photocrosslinked. Scanning electron microscopy images revealed that IPNs are denser than SIPNs, which results in their molecular reinforcement. This was further confirmed by rheological experiments. Because of the presence of the HA crosslinked network, the storage modulus of IPNs was almost two orders of magnitude higher than SIPNs. The degradation of the collagen–HA IPNs was slower than the SIPNs because of the presence of the crosslinked HA network. Increasing concentration of HA further altered the properties among IPNs. Cytocompatibility of IPNs was confirmed by Schwann cell and dermal fibroblasts adhesion and proliferation studies. We also fabricated patterned scaffolds with regions of IPNs and SIPNs within a bulk hydrogel, resulting in zonal distribution of crosslinking densities, viscoelasticities, water content and pore sizes at the micro- and macro-scales. With the ability to fine-tune the scaffold properties by performing structural modifications and to create patterned scaffolds, these hydrogels can be employed as potential candidates for regenerative medicine applications. [Copyright &y& Elsevier]

Abstract: Due to its hydrophobicity and negatively charged surfaces, PLGA-based scaffolds have encountered problems in controlled-release and tissue engineering applications. The effects of charge modification of PLGA micro-porous foams on DNA delivery and DNA transfection are investigated herein. Tailor-designed l-lysine peptides (K4 and K20) were employed to modify the surface charge of PLGA foams using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide cross linkers and the effects of charge modification of PLGA were examined in three main aspects: DNA adsorption, DNA release properties and DNA transfection. Successful conjugation of peptide and DNA adsorption were verified by X-ray photoelectron spectroscopy. A plasmid encoding bone morphogenetic protein-2 (BMP2) was used throughout the current study and the results indicate that adsorption capacity and release behavior of DNA were highly dependent on the charge properties of the foam surfaces. The release rates of DNA from the K4- and K20-functionalized foams are more sustainable as compared to the blank foam. As a result, the sustained release of DNA from modified foams led to negligible cytotoxicity and sustained expression of DNA which is favorable for DNA delivery and tissue engineering application. Furthermore, the ease of fabrication and modification of PLGA foams makes it a promising DNA delivery device. [Copyright &y& Elsevier]

Abstract: In this investigation, the fabrication, physico-chemical and biological characterization of a novel smart hydrogel had been evaluated for its potentials in effective controlling protein delivery. The hydrophilic pachyman-based hydrogel was generated facilely by crosslinking hydrosoluble carboxymethyl pachyman (CMP) with epichlorohydrin (ECH). The ECH concentration possessing maximum (99.7%) encapsulation efficiency and the most appropriate swelling characteristics was found to be 1.25% (w/v). The resultant hydrogel exhibited swelling ratios most favorable for drug release in simulated intestinal media. It could release two model protein drugs (bovine serum albumin and lysozyme) in the controlled manner and with full preservation of the protein stability and enzymatic activity. Importantly, the ECH-CMP hydrogel was confirmed to be biocompatible and biodegradable. From these findings, we were able to conclude that the synthesized pachyman-based hydrogel would be a promising delivery carrier candidate for site-specific delivery of protein drugs. [Copyright &y& Elsevier]

Copyright of Polimery is the property of Industrial Chemistry Research Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Drug delivery applications using biodegradable polymeric microspheres are becoming an important means of delivering therapeutic agents. The aim of this work was to modulate the microporosity of poly(ε-caprolactone) (PCL) microcarriers to control protein loading capability and release profile. PCL microparticles loaded with BSA (bovine serum albumin) have been de novo synthesized with double emulsion solvent evaporation technique transferred and adapted for different polymer concentrations (1.7 and 3% w/v) and stabilizer present in the inner aqueous phase (0.05, 0.5 and 1% w/v). SEM (scanning electron microscope) and CLSM (confocal laser scanning microscope) analysis map the drug distribution in homogeneously distributed cavities inside the microspheres with dimensions that can be modulated by varying double emulsion process parameters. The inner structure of BSA-loaded microspheres is greatly affected by the surfactant concentration in the internal aqueous phase, while a slight influence of polymer concentration in the oil phase was observed. The surfactant concentration mainly determines microspheres morphology, as well as drug release kinetics, as confirmed by our in-vitro BSA release study. Moreover, the entrapped protein remained unaltered during the protein encapsulation process, retaining its bio-activity and structure, as shown through a dedicated gel chromatographic analytical method. [ABSTRACT FROM AUTHOR]

A poly ( N-isopropylacrylamide) (PNIPA) hydrogel was synthesized by free radical polymerization and reinforced with a polyurethane foam to make a hydrogel composite. The temperature dependence of the elastic modulus of the PNIPA hydrogel and the composite due to volume phase transition was found using a uniaxial compression test, and the swelling property was investigated using an equilibrium swelling ratio experiment. The gel composite preserves the ability to undergo the volume phase transition and its elastic modulus has strong temperature dependence. The temperature dependence of the elastic modulus and swelling ratio of the gel composite were compared to the PNIPA hydrogel. Not surprisingly, the modulus and swelling ratio of the composite were less dramatic than in the gel. [ABSTRACT FROM AUTHOR]

We report a novel 3-D cavity wound dressing based on a hydrogel–elastomer Interpenetrating Polymer Network (IPN) fabricated into an open-mesh architecture. IPN fibers used to form the dressing were produced by a wet spinning method and optimized in two steps. A factorial experiment was first conducted to identify key parameters that controlled fiber properties. We observed that gelatin wt% played a major role in determining fiber yield, swelling, strength and stability. Other contributing factors included coagulation solution composition, gelatin type, and pre- and post-UV irradiation time. The key factors were then further evaluated individually to achieve a condition that provided a combination of good swelling, mechanical properties and stability. The concentration of the gelatin/HydroThaneTM extrusion solution significantly affected fiber formation and properties, presumably due to the changes in solution viscosity. The effects of pre-UV irradiation were also ascribed to its impact on the solution viscosity and became negligible at higher concentrations when viscosity is mainly controlled by concentration. The composition of the coagulation bath influenced the fiber swelling and wet stress. These results, taken together with our previous studies, suggest that our biomaterial would provide a combination of mechanical and swelling properties suitable for wound dressing applications. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) (PIPAAm) hydrogels grafted with lower critical solution temperature modulated polymers. Biomedical applications of PPAM gels; Methods; Results and discussion.

Thermally responsive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPA-co-AAm)) nanohydrogel (NHG) with a diameter of about 50 nm and a lower critical solution temperature (LCST) of about 40 degC was synthesized by a previously reported precipitation polymerization method. The physical properties including LCST, diameter and morphology were characterized. Four hydrophobic model drugs (5-fluorouracil (5-FU), fluorescein, docetaxel (DTX) and near-infrared dye-12 (NIRD-12)) with different hydrophilicities were respectively entrapped into the nanoparticles and their in vitro release kinetics from NHG was investigated. DTX was ultimately chosen as the goal anti-tumor drug and optimally entrapped into NHG with a drug loading content (DLC) of 7.38% and encapsulation efficiency (EE) of 73.8%. An in vitro drug release test indicated that DTX-loaded NHG had zero-order release kinetics at 43 degC. The respective anti-tumor efficacy of DTX-loaded NHG with or without hyperthermia on tumor tissue was evaluated in Kunming mice-bearing S180 sarcoma. The inhibition rates of DTX-loaded NHG with or without hyperthermia were 78.15% and 48.78%, respectively. DTX-loaded NHG also showed much lower toxicity during the therapeutic procedure. Results indicated that this kind of thermally responsive, drug-loaded NHG could be used as a promising strategy for tumor therapy with the help of local hyperthermia treatment. [ABSTRACT FROM AUTHOR]

The article focuses on the use of nanoparticles in delivering and transfection of therapeutic deoxyribonucleic acid (DNA) to cancer cells based on two studies. A targeted polymer nanoparticle was developed in the first study while epidermal growth factor receptor-targeted gelatine-based engineered nanocarriers were used in the other. The nanoparticle in the first study has an iron oxide nanoparticle core. They were used in the delivery of DNA encoding green-fluorescent protein (GFP) to tumor cells.

Abstract summary: To achieve controlled release of different growth factors at different periods (i.e. vascular endothelial growth factor (VEGF) followed by platelet-derived growth factor (PDGF)), and to investigate the effect of such release pattern on angiogenesis, we loaded model protein compounds BSA and lysozyme into microspheres based on PTMC with different molecular weights. Microspheres with size 1–50 µm and loading efficiencies higher than 75% were prepared. Microspheres loaded with VEGF and PDGF will be dispersed in PEG-PLA hydrogels and tested for stimulation of angiogenesis. [Copyright &y& Elsevier]