Integration of Biomaterials into Sensors Based on Organic Thin-Film Transistors.

Sensors based on organic thin-film transistors (OTFTs) present various advantages, including high sensitivity and mechanical flexibility, thus possessing potential applications such as wearable devices and biomedical electronics for health monitoring, etc. However, such applications are partially limited by the biocompatibility, biodegradability, and sensitivity to target analytes of OTFT-based sensors, which can be improved by the incorporation of diverse biomaterials. This article presents a brief review from the viewpoint of the type of the integrated biomaterials, including naturally occurring biomacromolecules such as proteins, enzymes, and deoxyribonucleic acid, as well as biocompatible polymers such as polylactide, poly(lactide-co-glycolide), poly(ethylene glycol), cellulose, polydimethylsiloxane, parylene, etc. It is believed that future work in this field should be devoted to the selectivity, sensitivity, and stability improvement as well as the high-level integration and sophistication on the basis of the OTFT-based sensors for physical, chemical, and biological sensing applications.

Co-exposure of polystyrene nanoplastics and copper induces development toxicity and intestinal mitochondrial dysfunction in vivo and in vitro.

Nanoplastics (NPs) have raised concerns about the combined toxicity to living organisms due to their ability to adsorb heavy metals. There is still uncertainty, however, whether NPs combined with heavy metals exert adverse effects on intestinal microenvironment, especially the intestinal cells and microbiota. Herein, the combined effects of 500 nm spherical-shaped polystyrene nanoplastics (PSNPs) and copper ions (Cu2+) on intestinal cells and gut microbiota were assessed using HCT-116 cells and zebrafish models. The combined exposure of PSNPs (10 mg/L) and Cu2+ (0.5 mg/L) induced more severer hatching interference of zebrafish embryos, deformation, and mortality. In larval stage, PSNPs (10 mg/L) accumulated and carried more Cu2+ in the gastrointestinal tract (GIT) of zebrafish after co-exposure for 5 days. Excessive neutrophil recruitment and oxidative stress in GIT of zebrafish larvae were observed. The mechanism of the combined toxicity was revealed by transmission electron microscopy (TEM) showing the injuries of GIT, transcriptome and 16S rDNA gene sequencing showing the toxicity pathways, including oxidative phosphorylation and respiratory electron transport chain, as well as microbial community analysis showing the induced microbiota dysbiosis. In vitro tests using HCT-116 cells showed that PSNPs (10 mg/L) and Cu2+ (0.5 mg/L) increased cell death while decreasing ATP concentration and mitochondrial membrane potential after 48 h exposure. These findings may provide new insights into the combined toxicity of nanoplastics and heavy metals in the intestinal microenvironment.

Anisotropic self-assembling micelles prepared by the direct dissolution of PLA/PEG block copolymers with a high PEG fraction.

A series of polylactide-poly(ethylene glycol) (PLA-PEG) block copolymers with a high PEG fraction were synthesized by the ring-opening polymerization of L- or D-lactide in the presence of mono- or dihydroxyl PEG using nontoxic zinc lactate as a catalyst. Micelles were then prepared by direct dissolution of the obtained water-soluble copolymers in an aqueous medium without heating or using any organic solvents. Large anisotropic micelles instead of conventional spherical ones were observed from a transmission electron microscopy examination. Various parameters influencing the structure of the novel micelles were considered, such as the copolymer chain structure, molar mass, PEG fraction, copolymer concentration, and stereocomplexation between L- and D-PLA blocks. Anisotropic micelles were obtained for both diblock and triblock copolymers but vanished with increasing molar mass of the copolymers. The morphology of micelles strongly depends on the PEG fraction. Anisotropic micelles were found only in an intermediate EO/LA ratio range in which a higher PEG fraction leads to a higher length/width ratio of micelles. Stereocomplexation between L- and D-PLA or a lower concentration disfavors the formation of anisotropic micelles. Under appropriate concentrations, spherical and anisotropic micelles coexist in the same micellar solution. Moreover, it was found that anisotropic micelles are susceptible to further self-assemble into more organized complex aggregates. Similar results were obtained from light scattering and aqueous gel permeation chromatography measurements. A novel model is proposed to explain the formation of anisotropic micelles and the effects of various parameters on the structure of micelles in an aqueous medium.

Novel biodegradable polylactide/poly(ethylene glycol) micelles prepared by direct dissolution method for controlled delivery of anticancer drugs.

PURPOSE: The aim of this study is to develop novel polylactide/poly(ethylene glycol) (PLA/PEG) micelles as carrier of hydrophobic drug (paclitaxel) by direct dissolution method without using any organic solvents. The in vitro and in vivo release properties were studied in comparison with micelles prepared by dialysis. METHODS: Drug encapsulation efficiency (EE) and loading content (LC) of the micelles were evaluated by high-performance liquid chromatography. Micelle diameters and structures were determined by dynamic light scattering and transmission electron microscopy. In vitro release was performed in phosphate-buffered saline (pH 7.4) at 37 degrees C, and in vivo experiments were realized in lung cancer-bearing mice. RESULTS: Similar EE and LC values were obtained for micelles by direct dissolution method and those by dialysis. L- and D-PLA/PEG mixed micelles present higher drug encapsulation ability than separate micelles due to stereocomplexation. Micelle diameters are enlarged by drug-loading. Faster drug release was obtained for micelles by direct dissolution than those by dialysis. Compared with current clinical formulation and micelles by dialysis, paclitaxel-loaded micelles by direct dissolution showed the highest antitumor ability. CONCLUSION: The L- and D-PLA/PEG mixed micelles by direct dissolution method present many advantages such as easy formulation and absence of toxic organic solvents, which shows great potential as carrier of hydrophobic drugs.

Highly sensitive and selective fluorescent detection of phosphate in water environment by a functionalized coordination polymer.

Phosphate, due to its somatotrophic effect on organisms, can cause severe eutrophication with excessive content in water. Conventional methods for phosphate detection, which are based on complicated instruments, are time-consuming. Here we report a luminescent lanthanide functionalized coordination polymer (Eu@BUC-14) by doping Eu3+ cations to BUC-14 nanocrystals. This Eu3+ functionalized hybrid (Eu@BUC-14) presents excellent luminescence features of Eu3+ ion that originated from efficient energy transfer from the ligand. The detection results show that Eu@BUC-14 is a highly efficient luminescent probe for phosphate detection in aqueous solutions, exhibiting high sensitivity with a low detection limit of 0.88 µM and a short response time of within 5 min. More significantly, Eu@BUC-14 has a high specificity for PO43- over fifteen other pollutant anions and eleven metal cations. The sensing mechanism is proposed via an in-depth analysis of the interaction between PO43- and Eu3+. Simultaneously, it displays high adsorption ability toward PO43- (57.9 mg P/g), making it an outstanding multifunctional material. And the adsorption process plays an important role in preconcentration of PO43- which can lead to a quick fluorescent response with high quenching efficiency. The practicality of Eu@BUC-14 was also validated by sensing PO43- in real environment water samples.

Effect of polymer degradation on prolonged release of paclitaxel from filomicelles of polylactide/poly(ethylene glycol) block copolymers.

Paclitaxel is one of the most efficient anticancer agents, but the conventional dosage formulations cause many side effects. PLA-PEG filomicelles are promising carriers of paclitaxel because high loading capacity and long term release can be achieved. Slow release of cytostatic drugs is very advantageous due to prolonged exposure of tumor cells to cytostatic over multiple cell cycles. The aim of this study was to evaluate the potential of bioresorbable PLA-PEG filomicelles for prolonged delivery of paclitaxel. Paclitaxel is encapsulated in PLLA-PEG filomicelles and PDLLA-PEG spherical micelles. Drug release was studied in PBS at 37°C at various pH values to elucidate the influence of polymer degradation on drug release. NMR, GPC and HPLC were used to follow polymer degradation and drug release. The release of paclitaxel is strongly dependent on the degradation of micelles. A biphasic drug release profile is observed for both PLLA-PEG and PDLLA-PEG micelles: slow release in the first phase and faster release in the second phase. Degradation is faster at acidic pH than at pH7.4, and PLLA-PEG filomicelles degrade less rapidly than PDLLA-PEG spherical micelles, leading to various rates of drug release. The correlation between degradation and drug release is very helpful for the development of novel drug carriers with tailored properties. Importantly, the cytotoxic activity of PLLA-PEG filomicelles was evidenced, thus showing their potential as carrier of antitumor drugs.

Self-assembled filomicelles prepared from polylactide/poly(ethylene glycol) block copolymers for anticancer drug delivery.

Bioresorbable filomicelles present many advantageous as drug delivery systems e.g., long circulation time and high loading efficiency. The aim of this study was to develop polylactide/poly(ethylene glycol) (PLA/PEG) filomicelles for drug delivery applications. A series of PLA/PEG diblock copolymers were synthesized using non-toxic initiator, and characterized by means of NMR and GPC. Analysis of morphology of micelles determined by TEM revealed that apart from the weight fraction also the molar mass of PEG and the stereochemistry of PLA block must be considered for tailoring micellar structures. The CMC was found to be dependent on the length and structure of the hydrophobic block. It was observed that the drug loading properties could be improved by selection of appropriate copolymer and encapsulation method. Slower release of paclitaxel was observed for mPEG5000 initiated copolymers than mPEG2000 initiated copolymers. Moreover, the influence of the length of hydrophobic block and its stereoisomeric form on drug release rate was evidenced. Therefore, PLA/PEG filomicelles with good stability, high drug loading capacity and sustained drug release appear most attractive for drug delivery applications.

Aggregates and hydrogels prepared by self-assembly of amphiphilic copolymers with surfactants.

A series of water-insoluble polylactide/poly(ethylene glycol) (PLA/PEG) block copolymers were synthesized by ring-opening polymerization of lactide in the presence of mono- or dihydroxyl PEG, using nontoxic zinc lactate as catalyst. Interactions between the resulting copolymers and sodium dodecyl sulfate (SDS) in water were studied by varying SDS fraction and copolymer concentration, using ultraviolet-visible spectrometer. Light transmission results show that all the insoluble copolymers strongly interact with SDS, and the solubility of the copolymers is improved with increasing SDS fraction. Copolymers with triblock structures or higher molar masses present larger variation of solubility as compared to those with diblock structures or lower molar masses. Transmission electron microscopy and dynamic light scattering were then employed to examine the microstructure of aggregates in the mixture solutions. Various aggregates such as vesicles, branch-like micelles, spherical micelles, or nanogels were observed, depending on the SDS fraction and copolymer concentration. It is assumed that at low SDS fractions, surfactant molecules attach to PLA segments and make the copolymers more soluble to form various aggregates. At high SDS fractions, junctions composed of SDS aggregates with PLA segments involved inside are formed in the case of triblock copolymers and diblock ones with high molar masses. These junctions lead to cross-linking of copolymer chains to yield a nanogel. Hydrogels can be obtained at high concentrations as confirmed by rheological measurements.

Novel thymopentin release systems prepared from bioresorbable PLA-PEG-PLA hydrogels.

Copolymers were synthesized by ring opening polymerization of l- or d-lactide in the presence of dihydroxyl PEG with molar mass of 6000, 12,000 and 20,000, using zinc lactate as catalyst. Bioresorbable hydrogels were obtained by mixing PLLA-PEG-PLLA and PDLA-PEG-PDLA aqueous solutions due to stereocomplexation between PLLA and PDLA chains. Rheological measurements show that the hydrogels present typical viscoelastic behaviors, although degradation could occur during the gelation process. Thymopentin was taken as a model drug to evaluate the potential of PLA-PEG-PLA hydrogels as carrier of hydrophilic drugs. Various parameters such as copolymer concentration, drug load, copolymer composition and the difference between sol and gel were considered. The release profiles are characterized by an initial burst followed by slower release. Higher copolymer concentration leads to slower release rate and less burst effect due to more compact structure which disfavors drug diffusion. Similarly, higher molar mass of the copolymers disfavors the release of TP5, and hydrogels composed of both PLLA/PEG and PDLA/PEG present slower release rates than single copolymer solutions. In contrast, drug load exhibits little influence on the release profiles due to the high water solubility of TP5. In all cases, nearly 80% of TP5 is released. In vivo studies proved the potential of TP5 containing hydrogels, especially those with a concentration of 25%. Both the CD4(+)/CD8(+) ratio and the morphology of thymus indicate the immunization efficacy of the TP5 release systems based on PLA/PEG hydrogels.