Synthesis of copolymer-stabilized silver nanoparticles for coating materials

Silver ions being less toxic than silver nanoparticles, a more safe material can be obtained to be used as antimicrobial coating. This can be achieved by using thiol chemistry and covalently attach the silver nanoparticles in the coating. Our aim is to produce a coating having antimicrobial properties of silver ions but with the silver nanoparticles firmly attached in the coating. Here, we present a way to produce silver nanoparticles that can be used as a component in a coating or as such to produce an antimicrobial coating. The silver nanoparticles presented here are stabilized by a copolymer (poly(butyl acrylate–methyl methacrylate)) that is soft and has well-known good film-producing properties. The reversible addition-fragmentation chain transfer radical polymerization technique used to prepare the polymers provides conveniently a thiol group for effective binding of the silver nanoparticles to the polymers and thus to the coating.     

Comparison of the preparation of PLGA–BSA nano- and microparticles by PVA, poloxamer and PVP

The objective of our study was to prepare nano- and microparticles economically considering some practical parameters such as size and encapsulation efficiency as well as ability of particle recovery. Bovine serum albumin (BSA) model protein was encapsulated by poly(d,l-lactide-co-glycolide) (PLGA) using a multiple water-in-oil-in-water emulsion-solvent evaporation technique. The effect of three surfactants: polyvinyl alcohol, poloxamer, and polyvinyl pyrrolidone, used in the outer water phase, on the properties of particles was investigated. The emulsifier/PLGA mass ratio played an important role in the preparation procedure of the particles. This ratio was found to be approximately 1 for polyvinyl alcohol (PVA) if the aim was to formulate nanoparticles with narrow size distribution (<220 nm), high yield and good encapsulation efficiency (>90%). Although, a ratio of 2:1 was sufficient to produce submicron particles by poloxamer with high yield, more than 70% and 90% encapsulation efficiency required minimum 4 and 10 emulsifier/PLGA mass ratio, respectively. Five times more PVA and 10 times more poloxamer than the PLGA mass were necessary to obtain nanoparticles which were easy to redisperse after centrifugation. Microparticles released more BSA than nanoparticles prepared by PVA, however, the situation was reverse with poloxamer. Microparticles formulated by polyvinyl pyrrolidone (PVP) showed the fastest in vitro release.     

Fluorescent π‐Conjugated Polymer Dots versus Self‐Assembled Small‐Molecule Nanoparticles: What’s the Difference?

Fluorescent nanoparticles based on π‐conjugated small molecules and polymers are two different classes of π‐conjugated systems that have attracted much interest. To date, both emerging classes have only been studied separately and showed no clear differences in their properties. Herein these nanoparticles are compared on the basis of a fluorene co‐polymer and its corresponding small molecule. Both systems formed nanoparticles with the same diameter, whereas the fluorescence properties clearly differed. In case of the polymer the fluorescence diminished, whereas for the small molecules the fluorescence increased. In addition, the capability of encapsulation and release of a hydrophobic dye from the fluorescent nanoparticles was studied. For the polymer system, encapsulation was highly efficient and no release was observed, whereas for the small molecule system encapsulation was less efficient and release of the dye was observed. These studies show a clear difference between small molecules and polymers which has important implications for the design of fluorescent nanoparticles.     

Sacrificial template-directed fabrication of superparamagnetic polymer microcontainers for pH-activated controlled release of Daunorubicin

Magnetic pH-sensitive microcontainers were produced by a four-step process. The first step involves the synthesis of citrate-modified magnetic nanoparticles via the coprecipitation method. The second step consists of the encapsulation of magnetic nanoparticles in non-cross-linked poly(methacrylic acid) (PMAA) microspheres through distillation precipitation polymerization, resulting in a core/shell structure. The third step concerns the formation of a poly(N,N'-methylenebis(acrylamide)-co-mathacrylic acid) (P(MBAAm-co-MAA)) layer on the surface of magnetic PMAA microspheres by second distillation precipitation polymerization in order to produce a trilayer hybrid microsphere. The last step deals with the removal of PMAA layer in ethanol and formation of a stable P(MBAAm-co-MAA) microcontainer with magnetic nanoparticles entrapped inside the formed cavity. This process is simple and leads to the formation of superparamagnetic pH-sensitive microcontainers. The structure and properties of the magnetic microcontainers were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), and dynamic light scattering (DLS) to determine the functionalities of the hybrid structure. The magnetic pH-sensitive microcontainers were loaded with Daunorubicin and tested with respect to release rate at different pH values in order to evaluate their functionality as controlled release system.     

麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

Multicomponent nanoparticles via self-assembly with cross-linked block copolymer surfactants

We describe a simple and versatile protocol to prepare water-soluble multifunctional nanostructures by encapsulation of different nanoparticles in shell cross-linked, block copolymer micelles. This method permits simultaneous incorporation of different nanoparticle properties within a nanoscale micellar container. We have demonstrated the co-encapsulation of magnetic (gamma-Fe2O3 and Fe3O4), semiconductor (CdSe/ZnS), and metal (Au) nanoparticles in different combinations to form multicomponent micelles that retain the precursor particles' distinct properties. Because these multifunctional hybrid nanostructures spontaneously assemble from solution by simultaneous desolvation of nanoparticles and amphiphilic block copolymer components, we anticipate that this can be used as a general protocol for preparing multifunctional nanostructures without explicit multimaterial synthesis or surface functionalization of nanoparticles.     

Comparative Study of Reversed-Phase High-Performance Liquid Chromatography and Ultraviolet–Visible Spectrophotometry to Determine Doxorubicin in pH-Sensitive Nanoparticles

Analytical methods by reversed-phase high-performance liquid chromatography (HPLC) and ultraviolet–visible spectrophotometry were developed and validated to determine doxorubicin in pH-sensitive chitosan nanoparticles. Chromatographic separation was performed on a reversed-phase C₁₈ column, with ultraviolet detection at 254?nm and a mobile phase composed by 90% (v/v) acetonitrile in water and water pH 3.0 (33:67, v/v). The spectrophotometry method had the wavelength set at 480?nm and pH 3.0 water was used as a diluent. Calibration curves were linear from 1 to 30?µg/?mL (r?>?0.9995) and the specificity was demonstrated by verifying the absence of interferences from nanoparticle components. The values of accuracy and precision were within the acceptable limits, and robustness studies were performed by a two-level full factorial design. The validated methods were further tested to assess doxorubicin content in six different batches of pH-sensitive chitosan nanoparticles. The comparative analyses showed nonsignificant differences (p?>?0.05). Likewise, the HPLC method was successfully applied to determine the drug encapsulation efficiency as well as to measure doxorubicin during in vitro release assays and degradation kinetic studies under ultraviolet light C irradiation. Both methods fulfilled all validation parameters and were shown to be suitable for the characterization of doxorubicin-loaded pH-sensitive chitosan nanoparticles, without interferences from nanoparticle matrix.     

pH敏感型mPEG-Hz-PLA聚合物纳米载药胶束的制备

以合成的含有腙键的聚乙二醇大分子(mPEG-Hz-OH)为引发剂,以丙交酯为单体引发开环聚合反应,并通过调整投料比,制备出3种不同分子量的含腙键的生物可降解嵌段聚合物(mPEG-Hz-PLA).将腙键引入到聚合物的骨架中,以此构建聚合物胶束并作为pH敏感型纳米药物载体.制备的pH敏感型胶束的CMC值等于或低于5.46×10-4 mg/m L,DLS和TEM显示粒径均小于100 nm,且粒径分布均匀.非pH敏感型胶束在不同pH下的粒径变化不明显,而pH敏感型胶束在酸性环境下(pH=4.0和pH=5.0)胶束粒径出现了明显变化.以阿霉素为模型药物制备了pH敏感型载药胶束,其粒径比空白胶束大(100~200 nm),且粒径分布均匀.药物释放实验表明pH敏感型载药胶束随着释放介质pH降低累积释药量增高.MTT实验表明空白胶束对HeLa细胞和RAW264.7细胞几乎没有抑制作用,而载阿霉素的胶束对2种细胞的抑制作用都随着剂量的增大和时间的延长而增强.     

Triclosan-loaded with high encapsulation efficiency into PLA nanoparticles coated with β-cyclodextrin polymer

The purpose was to prepare triclosan-loaded polylactic acid nanoparticles containing β-cyclodextrin polymer shell, evaluate triclosan release from the particles using Franz diffusion cells and to study the stability of the particles in presence of a model protein, bovine serum albumin. The nanoparticles were prepared by a solvent displacement process. The nanoparticles were characterized by their size, encapsulation efficiency and morphology. They were of spherical shape with hydrodynamic diameter of about 100 or 200 nm depending on the polylactic acid used. Their high encapsulation efficiency (~90%) indicated that triclosan is easily incorporated into the nanoparticles. The nanoparticles displayed slow and sustained triclosan release patterns (diffusion coefficient about 10^?22 m²/s) and the β-cyclodextrin polymer coating was stable under simulated physiological conditions. All these data indicated that these novel core–shell nanoparticles might provide a promising carrier system for controlled release of triclosan and other hydrophobic drugs after systemic administration.     

Physicochemical and anti-bacterial performance characterization of clarithromycin nanoparticles as colloidal drug delivery system

The objective of the present study was to prepare clarithromycin (CLR) loaded biodegradable nanoparticles (NPS), with a view to investigate its physicochemical properties and anti-bacterial activity. PLGA was used as a biodegradable polymer and the particles were prepared by nano-precipitation method in 3 different drugs to polymer ratios. Evaluation of the physicochemical properties of the prepared nanoparticles was performed using encapsulation efficiency, nanoparticle production yield, dissolution studies, particle size analysis, zeta potential determination, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffractometry. The antimicrobial activity against Staphylococcus aureus was determined using serial dilution technique to achieve the minimum inhibitory concentration (MIC) of NPs. The particles were between 189 and 280 nm in size with narrow size distribution, spherical shape and 57.4-80.2% entrapment efficiency. Zeta potential of the NPs was fairly negative. The DSC thermograms and X-ray diffraction patterns revealed reduced drug crystallinity in the NPs. FT-IR spectroscopy demonstrated possible noncovalent interactions between the drug and polymer. In vitro release study showed an initial burst followed by a plateau during a period of 24 h. The NPs were more effective than intact CLR against S. aureus so that the former showed equal antibacterial effect at 1/8 concentration of the intact drug. In conclusion, the prepared CLR nanoparticles are more potent against S. aureus with improved MICs and appropriate physicochemical properties that may be useful for other susceptible microorganisms and could be an appropriate candidate for intravenous, ocular and oral and topical preparations.     

Surface Modification of Functional Nanoparticles for Controlled Drug Delivery

Abstract

Surface‐modified nanoparticles have received much attention as drug carriers. Natural and synthetic polymers are used as the materials to prepare nanoparticles and the properties of these nanoparticles originate with these polymeric materials. In particular, these nanoparticles are modified for specific objectives. The surface characteristics of (shell) nanoparticles are more important than those of the core, because the shell layer directly contacts body fluids and organs. Generally, the nanoparticles are coated with hydrophilic polymer to give long circulation and/or are conjugated with functional ligands or proteins for site‐specific delivery. In this review, the preparative methods and the applications of surface modification of polymeric functionalized nanoparticles for long‐circulation, site‐specific delivery, and oral delivery are discussed.     

Weak polyelectrolyte control of carbon nanotube dispersion in water

The dispersion of nanotubes by pH-responsive polymers (i.e., weak polyelectrolytes) enables the macroscopic properties of aqueous suspensions to be tuned. Microstructural changes were achieved as a function of pH in aqueous suspensions containing single-walled carbon nanotubes and imaged by cryogenic-TEM. Clear evidence of pH-sensitive nanotube dispersion is shown. We expect that many useful properties of these nanotube-polymer systems could be sensitive to microstructure, making this technique important for aqueous processing of carbon nanotubes and macroscopic tailoring of solid polymer nanocomposite behavior.     

Controllable Assembly and Separation of Colloidal Nanoparticles through a One‐Tube Synthesis Based on Density Gradient Centrifugation

Self‐assembly of gold nanoparticles into one‐dimensional (1D) nanostructures with finite primary units was achieved by introducing a thin salt (NaCl) solution layer into density gradient before centrifugation. The electrostatic interactions between Au nanoparticles would be affected and cause 1D assembly upon passing through the salt layer. A negatively charged polymer such as poly(acrylic acid) was used as an encapsulation/stabilization layer to help the formation of 1D Au assemblies, which were subsequently sorted according to unit numbers at succeeding separation zones. A centrifugal field was introduced as the external field to overcome the random Brownian motion of NPs and benefit the assembly effect. Such a facile “one‐tube synthesis” approach couples assembly and separation in one centrifuge tube by centrifuging once. The method can be tuned by changing the concentration of interference salt layer, encapsulation layer, and centrifugation rate. Furthermore, positively charged fluorescent polymers such as perylenediimide‐poly(N,N‐diethylaminoethyl methacrylate) could encapsulate the assemblies to give tunable fluorescence properties.     

Design and use of organic nanoparticles prepared from star-shaped polymers with reactive end groups

Star-shaped poly(isobornyl acrylate) (PiBA) was prepared by atom transfer radical polymerization (ATRP) using multifunctional initiators. The optimal ATRP conditions were determined to minimize star-star coupling and to preserve high end group functionality (>90%). Star-shaped PiBA with a narrow polydispersity index was synthesized with 4, 6, and 12 arms and of varying molecular weight (10,000 to 100,000 g x mol(-1)) using 4 equiv of a Cu(I)Br/PMDETA catalyst system in acetone. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis, NMR spectroscopy, and size exclusion chromatography (SEC) confirmed their controlled synthesis. The bromine end group of each arm was then transformed to a reactive end group by a nucleophilic substitution with methacrylic acid or cinnamic acid (conversion >90%). These reactive star polymers were used to prepare PiBA nanoparticles by intramolecular polymerization of the end groups. The successful preparation of this new type of organic nanoparticles on a multigram scale was proven by NMR spectroscopy and SEC. Subsequently, they have been used as additives for linear, rubbery poly(n-butyl acrylate). Rheology measurements indicated that the viscoelastic properties of the resulting materials can be fine-tuned by changing the amount of incorporated nanoparticles (1-20 wt %), as a result of the entanglements between the nanoparticles and the linear polymers.     

Poly(vinyl ethers) as building blocks for new materials

The living cationic polymerization of vinyl ethers has been used to prepare a number of new polymers with special properties. Sequential polymerization of the hydrophilic methyl vinyl ether (MVE) and the hydrophobic octadecyl vinyl ether (ODVE) has lead to amphiphilic block-copolymers with emulsifying properties for water/decane mixtures. Poly(vinyl-ether) macromonomers were obtained by end-capping of living polymers with hydroxyethyl acrylate. Copolymerization of polyODVE-macromonomer with usual acrylates lead to highly branched hydrophobic polymers. When the end-capping was performed with bifunctionally living polymers, the corresponding “bis-macromonomers” were obtained. Copolymerization of such bis-macromonomers with styrene or butyl acrylate, leads to the formation of segmented polymer networks. In the case of polyODVE-poly(butyl acrylate), these networks showed a pronounced phase separation. Due to the crystallinity of the polyODVE domains, these materials showed shape memory properties.     

Block copolymer composition drives function of self‐assembled nanoparticles for delivery of small‐molecule cargo

Nanoparticles are useful for the delivery of small molecule therapeutics, increasing their solubility, in vivo residence time, and stability. Here, we used organocatalytic ring opening polymerization to produce amphiphilic block copolymers for the formation of nanoparticle drug carriers with enhanced stability, cargo encapsulation, and sustained delivery. These polymers comprised blocks of poly(ethylene glycol) (PEG), poly(valerolactone) (PVL), and poly(lactide) (PLA). Four particle chemistries were examined: (a) PEG‐PLA, (b) PEG‐PVL, (c) a physical mixture of PEG–PLA and PEG–PVL, and (d) PEG–PVL–PLA tri‐block copolymers. Nanoparticle stability was assessed at room temperature (20 °C; pH = 7), physiological temperature (37 °C; pH = 7), in acidic media (37 °C; pH = 2), and with a digestive enzyme (lipase; 37 °C; pH = 7.4). PVL‐based nanoparticles demonstrated the highest level of stability at room temperature, 37 °C and acidic conditions, but were rapidly degraded by lipase. Moreover, PVL‐based nanoparticles demonstrated good cargo encapsulation, but rapid release. In contrast, PLA‐based nanoparticles demonstrated poor stability and encapsulation, but sustained release. The PEG–PVL–PLA nanoparticles exhibited the best combination of stability, encapsulation, and release properties. Our results demonstrate the ability to tune nanoparticle properties by modifying the polymeric architecture and composition. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1322–1332     

Encapsulation and selective recognition of molecularly imprinted theophylline and 17beta-estradiol nanoparticles within electrospun polymer nanofibers

Molecularly imprinted nanoparticles are cross-linked polymer colloids containing tailor-made molecular recognition sites. In this study, molecularly imprinted nanoparticles were easily encapsulated within polymer nanofibers using an electrospinning technique to produce a new type of molecular recognition material. Poly(ethylene terephthalate) (PET) was used as the supporting nanofibers matrix to encapsulate theophylline and 17beta-estradiol imprinted nanoparticles. The composite nanofibers had an average diameter of 150-300 nm, depending on the content of molecularly imprinted nanoparticles. For the theophylline and 17beta-estradiol imprinted polymers, an optimal loading of molecularly imprinted nanoparticles was 25-37.5 wt % based on PET. The composite nanofibers prepared under these conditions had a well-defined morphology and displayed the best selective target recognition. Our approach of electrospinning-for-molecularly imprinted nanoparticles-encapsulation has unique advantages and opens new application opportunities for molecularly imprinted nanoparticles and electrospun nanofibers.     

Polyphosphazene nanoparticles for cytoplasmic release of doxorubicin with improved cytotoxicity against Dox-resistant tumor cells

This study involved the construction of self-assembled nanoparticles from novel pH-sensitive amphiphilic polyphosphazenes. These nanoparticles provide fast pH-responsive drug release and have the capability to disturb endosomal membranes. The polymers were prepared by linking N,N-diisopropylethylenediamine (DPA) onto a backbone of PEGylated polyphosphazene. In vitro cell viability measurements demonstrated the superior efficacy of these pH-responsive nanoparticles over free doxorubicin (Dox): the IC50 was over 60 times lower than that of free Dox against a Dox-resistant cell line. Using flow cytometry and confocal microscopy, the further investigation of the intracellular distribution of Dox and fluorescent probes provided evidence that, upon internalization by cells through endocytic pathways, the pH-sensitive polymer would disrupt membranes of endosomal compartments, releasing the cargo drugs into the cytoplasm in a burst-like manner. This resulted in reduced likelihood of drug efflux via exocytosis, and reversal of the drug resistance of the tumor cells. Generally, the pH-responsive nanoparticles designed in this study have achieved their potential as a drug delivery system for tumor therapy applications.     

Preparation and Evaluation of Propranolol-Imprinted Monolithic Stationary Phase by In Situ Technique and Application in Analysis of Propranolol in Biological Samples

Abstract

A propranolol molecule-imprinted monolithic stationary phase (MIMSP) was synthesized by in situ technique. The recognition mechanism of the polymers and the influences of some chromatographic conditions were examined by high-performance liquid chromatography (HPLC). The imprinted polymers showed much higher selectivity for β-blockers than the nonimprinted polymers (NIPs) did, which proves the successful preparation of propranolol-imprinted polymers by using an in situ technique. Then, this technique was used to prepare a molecularly imprinted polymer solid-phase extraction column to concentrate propranolol from biological samples. The results showed that the imprinted solid-phase extraction column could selectively enrich and purify propranolol from biological samples, such as plasma.     

Protein-loaded PLGA–PEO blend nanoparticles: encapsulation, release and degradation characteristics

The aim of this work was to study the variables that affect the encapsulation and release of proteins from nanoparticles based on poly(lactic-co-glycolic acid; PLGA)–poloxamer and PLGA–poloxamine blend matrices, using bovine serum albumin (BSA) and immuno-γ-globulin (IgG) as model proteins. The nanoparticles were prepared by a solvent diffusion technique, and the studied variables were (1) PLGA molecular weight, (2) type of PEO-block copolymers, (3) protein loading, (4) pH and, (5) volume of the protein solution. Our results showed that the proteins can be efficiently incorporated into and released from the blend matrices. The type of the PEO derivative and the pH of the internal aqueous phase were the most important factors influencing protein encapsulation and release kinetics. Moreover, comparative degradation study of PLGA, PLGA–poloxamer and PLGA–poloxamine nanoparticles confirmed that the degradation and release characteristics of polyester particles can be improved by the incorporation of polyoxyethylene derivatives with different hydrophilia–lipophilia balance.