PEGylation as a tool for the biomedical engineering of surface modified microparticles

Microparticles are of considerable interest for drug delivery, vaccination and diagnostic imaging. In order to obtain microparticles with long circulation times, or to provide the prerequisite for tissue specific targeting through decoration with suitable ligands, their surfaces need to be modified such that they become repellent to the adsorption of opsonic proteins and resistant to unspecific phagocytosis. The currently most considered strategy relies on the immobilisation of a poly(ethylene glycol) (PEG) corona onto the microparticles' surface. In the first chapter of this review, we discuss the unique physicochemical properties of PEG, which make it the polymer of choice to render the surfaces of microparticles repellent to the adsorption of proteins and resistant to cellular recognition. Furthermore, we present various technologies for the preparation of microparticles with PEGylated surfaces. Another aspect is the decoration of the PEGylated surfaces with suitable ligands for cell specific recognition and targeting. Finally, we review miscellaneous applications of PEGylated microparticles, mainly focusing on the fields of drug delivery, targeting and vaccination. Although still in its infancy, the PEGylation of microparticles holds promise towards future biomedical applications.     

Electrochemical and surface studies on chemically modified glucose derivatives as environmentally benign corrosion inhibitors

Three glucose derivatives, namely Ethylenediamine-modified glucose, Tetramethylenediamine-modified glucose, and Hexamethylenediamine-modified glucose with three different carbon chain lengths were synthesized using environmentally benign and low-cost reactants at ambient temperature. The synthesized derivatives were evaluated as inhibitors for mild steel corrosion in 1 M HCl using electrochemical, surface analysis (XPS, AFM and contact angle), as well as computational (DFT) techniques. The obtained results suggest that the synthesized glucose derivatives significantly mitigate the corrosion of mild steel and show a rise in the inhibition efficiency with increasing inhibitor dosage. The inhibitor adsorption obeyed the Langmuir isotherm. The XPS analyses provided an elucidation on the interaction of the inhibitors with the steel substrate. The DFT studies showed that the protonated forms of the inhibitors act more prominently compared to the neutral form. The inhibitor HMG having the alkyl chain with six carbon atoms exhibited the highest inhibition performance of >95% at 22.71 × 10^?5 mol L^?1.     

表面麻醉白内障超声乳化人工晶体植入术的临床观察

目的 :探讨表面麻醉白内障超声乳化人工晶体植入术的优点和适应证。方法 :10 1例 (10 7只眼 )白内障患者采用表面麻醉下超声乳化白内障吸除术 ,同时植入人工晶体。结果 :表面麻醉下超声乳化白内障吸除术与常规麻醉手术相比 ,具有手术时间短、术后恢复快、并发症少等优点。结论 :具有一定手术经验的医师行表面麻醉下超声乳化白内障吸除人工晶体植入术疗效满意安全     

Tissue reaction after implantation of ceramic biomaterials with introduced electrokinetic zeta potential on surface

Studies over implants showed, that not only the kind of structure of material, but also the character of surface influences the local reaction. Endeavour to obtain the best possible biological properties of implants, intended to supplementing of osseous decreases, contributed to carrying out investigations over implants about active surface. Electrochemical reactions, occurring on implants surface, lead to beginning of electric occurrences on implant/tissue interface and beginning of so-called potential zeta. Utilization of these properties in implantology, induced us to carry out experimental studies with use of biomaterials with modified surface and of influence of potential zeta on biocompatibility. The carried out studies referred: to comparative investigations of tissue reaction of implants ceramic with of solid and porous surface, and to influence of electric load zeta on tissue reaction. For the studies were used 3 kinds of ceramics: porous, solid and solid ceramics with potential zeta (silanovated). The studies were carried out on 50 rats, to which studied ceramics was implanted into back muscles. Pathomorphological assessments were carried out 1, 4, 12, 26 and 32 weeks after implantation. The results of pathomorphological studies after implantation of ceramics solid and solid silanovated showed, that already after 1 week was formed thin membrane with visible, small blood-vessels. After 32 weeks it was significantly thicker. The produced capsule was strongly connected with surrounding muscles, and from side the implant adhered to it's surface. In case of implants of porous ceramics, already after 1 week the produced capsule of connective tissue was clearly thicker, and after 32 weeks it was, whitish, opaque, strongly connected to surrounding muscles. From side implant it became rooted in pores of ceramics. In microscopic studies it was shown, that both in early and distant period, the character and size of tissue reaction was dependent on structures of implant surface. Porous ceramics implanted in soft tissues, produced stronger inflammatory reaction being characterized with long lasting phase infiltration, which drove to producing thick connective tissue capsule. 32 weeks after implantation in the produced capsule these were visible former focuses of chondroid tissue. Reaction tissue occurring round solid ceramics, was characterized with shorter and less intensive proliferation phase. After 32 weeks visible former thin connective tissue capsule was visible. Ceramics with potential zeta (silanovated) generated minimum-tissue reaction, without visible proliferation phase. Studies in light and scanning microscopes, executed 32 weeks after implantation showed, that in produced thin layer of connective tissue were visible with adamantinating and calcifications focuses, and on the surface of ceramics were formed osseous tin plates.     

A novel surface modified nitrendipine nanocrystals with enhancement of bioavailability and stability

In this study, chitosan, a cationic polymer with positive charge, was introduced to modify the nanocrystals of nitrendipine with negative charge. The nanocrystals were prepared via precipitation-high pressure homogenization method. Then the nanocrystals were dispersed into chitosan solution, and the free chitosan was removed by centrifugation to obtain the chitosan modified nanocrystals, which remained the same particle size. However, the zeta-potential changed to positive after modification. The physical stability of the chitosan modified nanocrystals was remarkably improved under ambient conditions. During the in vitro dissolution test, the modified nanocrystals showed a certain degree of slow-release property. In the in vivo study, the C(max) of nitrendipine remained the same, however, the T(max) delayed from 0.75 h to 1.5 h with the chitosan modified nanocrystals. The surface modification by chitosan improved the bioavailability compared with the initial nanocrystals, which had demonstrated significant improvement of bioavailability compared to the traditional coarse powder form. Based on the experimental results, modification of the nanocrystals with certain polymer was supposed to be a good method to control the in vitro and in vivo behaviors of the nanocrystals, which could further increase the bioavailability of the water insoluble drug.     

Toxicology of chemically modified graphene-based materials for medical application

This review article aims to provide an overview of chemically modified graphene, and graphene oxide (GO), and their impact on toxicology when present in biological systems. Graphene is one of the most promising nanomaterials due to unique physicochemical properties including enhanced optical, thermal, and electrically conductive behavior in addition to mechanical strength and high surface-to-volume ratio. Graphene-based nanomaterials have received much attention over the last 5 years in the biomedical field ranging from their use as polymeric conduits for nerve regeneration, carriers for targeted drug delivery and in the treatment of cancer via photo-thermal therapy. Both in vitro and in vivo biological studies of graphene-based nanomaterials help understand their relative toxicity and biocompatibility when used for biomedical applications. Several studies investigating important material properties such as surface charge, concentration, shape, size, structural defects, and chemical functional groups relate to their safety profile and influence cyto- and geno-toxicology. In this review, we highlight the most recent studies of graphene-based nanomaterials and outline their unique properties, which determine their interactions under a range of environmental conditions. The advent of graphene technology has led to many promising new opportunities for future applications in the field of electronics, biotechnology, and nanomedicine to aid in the diagnosis and treatment of a variety of debilitating diseases.     

Cellulose materials modified by antiseptics and their antimicrobial properties

Adsorption properties of dressing cellulose materials with respect to surfactant antiseptics were studied. These antiseptics are a complex of the copolymer of N-vinylpyrrolidone and crotonic acid with dimethylbenzylalkylammonium chloride (a synthetic polymer with a wide spectrum of antimicrobial effect) and its low molecular weight analogue (dimethylbenzylalkylammonium chloride). It was established that cellulose materials reversibly adsorb mentioned surfactant antiseptics depending on their concentration in the initial solutions. Maximum release of surfactant antiseptics is achieved at solutions at pH = 7.0. Microbiological tests of cellulose materials modified by antiseptics have shown that they exhibit antimicrobial activity. These results can be used in medical practice in clinics for imparting antimicrobial properties to dressing materials.     

Silica nanoparticles modified with aminosilanes as carriers for plasmid DNA

We synthesised silica nanoparticles (SiNP) with covalently linked cationic surface modifications and demonstrated their ability to electrostatically bind, condense and protect plasmid DNA. These particles might be utilised as DNA carriers for gene delivery. All nanoparticles were sized between 10 and 100 nm and displayed surface charge potentials from +7 to +31 mV at pH 7.4. They were produced by modification of commercially available (IPAST) or in-house synthesised silica particles with either N-(2-aminoethyl)-3-aminopropyltrimethoxysilane or N-(6-aminohexyl)-3-aminopropyltrimethoxysilane. All particles formed complexes with pCMVbeta plasmid DNA as evidenced by ratio dependent retardation of DNA in the agarose gel and co-sedimentation of soluble DNA with nanoparticles. High salt and alkaline pH did inhibit complex formation. Absorption onto the particles also decreased the hydrodynamic dimensions of plasmid DNA as shown by photon correlation spectroscopy. Complexes formed in water at a w/w ratio of Si26H:DNA (pCMVbeta) of 300 were smallest with a mean hydrodynamic diameter of 83 nm. For effective condensation a w/w ratio of Si26H:DNA of 30 was sufficient. Further, the absorbed DNA was protected from enzymatic degradation by DNase I.     

Determination of dipyridamole by modified extraction-gravimetry with a surface acoustic wave resonator sensor

A simple and sensitive extraction-gravimetric method for the determination of dipyridamole is presented. The method is based on the extraction of free dipyridamole with chloroform, after neutralization with a basic agent, followed by measurement of the frequency shift response of the specially designed surface acoustic wave resonator sensor after evaporation of the extractant from the surface of the resonator. The frequency shift response was proportional to the amount of dipyridamole in the range 0.065–1.12 μg. Experimental parameters and the effect of interfering substances on the assay of dipyridamole were also examined in this study. The method was applied to the determination of dipyridamole in tablets.     

Physico-chemical characterisation of surface modified particles for inhalation

Surface modification of drugs for inhalation is a possibility to influence interparticulate forces. This can be necessary to achieve a sufficient aerosolisation during powder inhalation as the cohesiveness of the micronised drug can be reduced. In addition, the interaction with propellants in pressurised metered dose inhaler can be changed. This can be used to improve the physical stability of the suspension based formulations. A dry particle coating process was used for the alteration of particle surfaces. The blending of micronised salbutamol sulphate (SBS) with different concentrations of magnesium stearate (Mgst) or glycerol monostearate (GMS) was followed by co-milling with an air jet mill.     

Preparation and characterization of gelatin surface modified PLGA microspheres

This study optimized conditions for preparing and characterizing gelatin surface modified poly (lactic-co-glycolic acid) (PLGA) copolymer microspheres and determined this systems interaction with fibronectin. Some gelatin microspheres have an affinity for fibronectin-bearing surfaces; these miscrospheres exploit the interaction between gelatin and fibronectin. PLGA copolymer microspheres were selected because they have reproducible and slowrelease characteristics in vivo. The PLGA microspheres were surface modified with gelatin to impart fibronectin recognition. Dexamethasone was incorporated into these microspheres because dexamethasone is beneficial in chronic human diseases associated with extra fibronectin expression (eg, cardiovascular disease, inflammatory disorders, rheumatoid arthritis). The gelatin surface modified PLGA microspheres (prepared by adsorption, conjugation, and spray coating) were investigated and characterized by encapsulation efficiency, particle size, in vitro release, and affinity for fibronectin. The gelatincoated PLGA microspheres had higher interaction with fibronectin compared with the other gelatin surface modified PLGA microspheres (adsorption and conjugation). Dexamethasone was released slowly (over 21 days) from gelatin surface modified PLGA microspheres.     

The effect of surface phenomena on the processing of solid materials. I. Theoretical basis of surface phenomena of solid materials

The functions of friction and adhesion in the processing of solid materials were evaluated in our work. The first part of our study dealt with the theoretical basis of these phenomena. The work of Podczek was used as a guideline. The negative and positive effects of these parameters were emphasized. The types of adhesion were discussed. The different types of forces (capillary, Lifshitz-van der Waals, electrical, etc.) and several other parameters (surface free energy, roughness, particle size and shape) causing these effects were analysed. Different mathematical models which can be used for the determination of surface free energy, adhesion force and spreading coefficient were considered.     

The effect of surface phenomena on the processing of solid materials. II. Experimental evaluation of surface phenomena of solid materials

The functions of friction and adhesion in the processing of solid materials were evaluated in our work. The second part of our study dealt with some practical examples from our practice. Indomethacin was used for the examination of adhesion, dimenhydrinate for the study of friction, and metronidazole for the determination of the spreading coefficient. Several technological methods (coating, granulation, pelletization and tableting) were used. The positive effects of the processes on the various phenomena (surface free energy, adhesion force and spreading coefficient) were emphasized. The influences of alteration in the parameters on the flowability, compressibility, compact texture, etc. were assessed.     

Dissolution of materials in artificial skin surface film liquids

The dissolution of chemical constituents from jewelry, textiles, cosmetics, drugs, industrial chemicals, and particles in direct and prolonged contact with human skin is often assessed in vitro using artificial skin surface film liquids (SSFL). To provide meaningful results, the composition of artificial SSFL should accurately mimic human sweat and sebum, and the conditions of the in vitro test system should accurately reflect in vivo skin conditions. We summarized the reported composition of human SSFL and compared it to 45 different formulations of artificial sweat and 18 formulations of artificial sebum (studies published from 1940 to 2005). Conditions of in vitro dissolution test systems were reviewed and compared to in vivo skin conditions. The concentrations of individual constituents and pH of artificial sweat and concentrations of artificial sebum constituents are not always within ranges reported for human SSFL. Nearly all artificial SSFL lack many of the constituents in human SSFL. To develop a comprehensive model SSFL, we propose a standard SSFL, modified from the two best published sweat and sebum formulations. Little is known concerning the influence of test system conditions on dissolution, including SSFL temperature, container material composition, agitation, and physicochemical properties of the test article on dissolution. Thus, both a need and an opportunity exist for standardizing the composition of artificial SSFL and in vitro dissolution test methodologies. To standardize in vitro dissolution test systems, we recommend: maintaining artificial SSFL at a biologically relevant temperature appropriate to the human activity being modeled, carefully selecting test and sample storage containers to avoid bias in dissolution measurements, accounting for friction between a test article and skin in a biologically plausible manner, and physicochemical characterization of the test article or material to better understand mechanisms of dissolution and potential mechanisms of toxic action of dissolved material. More accurate modeling and better understanding of chemical dissolution from articles in contact with the skin will ultimately improve risk decision making, thereby protecting even the most susceptible persons from adverse health effects resulting from skin exposure.     

Melittin liposomes surface modified with poloxamer 188: in vitro characterization and in vivo evaluation

Melittin liposomes surface modified with poloxamer 188 were developed, and the effect of poloxamer 188 was investigated with regard to anti-cancer effect and vascular stimulation. Melittin liposomes surface modified with poloxamer 188 at different concentrations (0%, 2%, and 5%) were prepared using the adsorption method, followed by in vitro characterization, including entrapment efficiency, zeta potential, particle size, and morphology. Subsequently, the influence of repeated freeze-thawing on the liposomes was investigated, and the effect of poloxamer 188 on the repeated freeze-thawing process was explored. Vascular stimulation effects of MLT, and MLT liposome that surface coated with or without poloxamer were all studied. Pharmacokinetics of the different MLT preparations were determined and the anticancer activity of the MLT formulations was investigated. The particle size of the liposomes gradually increased with increasing poloxamer 188 content, while the entrapment efficiency did not change significantly. After the first freeze-thaw cycle, size and PDI were both markedly reduced, entrapment efficiency rose, and there was no significant change of zeta potential. The vascular irritation caused by MLT could be reduced to an extent by encapsulation in liposome, but not completely eliminated, while liposomes coated with poloxamer 188 can effectively abolish the phenomenon. Melittin liposomes with surface modified by poloxamer exhibit enhanced bioavailability, effective anticancer activity, and reduced side effects compared with melittin solution. Poloxamer plays an important role in melittin liposomes.     

Polylactide-co-glycolide microparticles with surface adsorbed antigens as vaccine delivery systems

Several groups have shown that vaccine antigens can be encapsulated within polymeric microparticles and can serve as potent antigen delivery systems. We have recently shown that an alternative approach involving charged polylactide co-glycolide (PLG) microparticles with surface adsorbed antigen(s) can also be used to deliver antigen into antigen presenting cell (APC). We have described the preparation of cationic and anionic PLG microparticles which have been used to adsorb a variety of agents, which include plasmid DNA, recombinant proteins and adjuvant active oligonucleotides. These PLG microparticles were prepared using a w/o/w solvent evaporation process in the presence of the anionic surfactants, including DSS (dioctyl sodium sulfosuccinate) or cationic surfactants, including CTAB (hexadecyl trimethyl ammonium bromide). Antigen binding to the charged PLG microparticles was influenced by several factors including electrostatic and hydrophobic interactions. These microparticle based formulations resulted in the induction of significantly enhanced immune responses in comparison to alum. The surface adsorbed microparticle formulation offers an alternative and novel way of delivering antigens in a vaccine formulation.     

Stem cell responses to plasma surface modified electrospun polyurethane scaffolds

The topographical effects from functional materials on stem cell behavior are currently of interest in tissue engineering and regenerative medicine. Here we investigate the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell (hESC) and rat postnatal neural stem cell (NSC) responses. The plasma gases were found to induce three combinations of fiber surface functionalities and roughness textures. On randomly oriented fibers, plasma treatments lead to substantially increased hESC attachment and proliferation as compared to native fibers. Argon plasma was found to induce the most optimal combination of surface functionality and roughness for cell expansion. Contact guided migration of cells and alignment of cell processes were observed on aligned fibers. Neuronal differentiation around 5% was found for all samples and was not significantly affected by the induced variations of surface functional group distribution or individual fiber topography.From the Clinical EditorIn this study the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell and rat postnatal neural stem cell (NSC) responses is studied with the goal of clarifying the potential effects of functional materials on stem cell behavior, a topic of substantial interest in tissue engineering and regenerative medicine.