Poly(acrylamide)-co-poly(hydroxyethyl)methacrylate-co-poly(cyclohexyl methacrylate) hydrogel platform for stability, storage and biocatalytic applications of urease.

In our present work, an explicit crosslinked thermo-responsive hydrogel platform has been developed, by using polyacrylamide (PAAm), poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(cyclohexyl methacrylate) (PCHMA), and then coupled with urease to yield bioconjugates (BCs). Synergic effect of these polymer units provides thermoresponsive nature, optimum crosslinking with desired swelling behaviour, and stability and improved catalytic to Urease in the resultant BCs. Synthesis of the terpolymer has been achieved by employing HEMA (monomer as well as crosslinker), instead of using the conventional crosslinkers, through free radical solution polymerization technique. Various grades of TRPUBs have been fabricated by varying HEMA and CHMA contents while keeping fixed amounts of AAm. Further, the structural analysis of BCs has been done by fourier transform infra-red spectroscopic study and their thermal stabilities have been studied by thermogravimetric analysis. Urea present in TRPUBs has beenanalysed for its hydrolysis atdifferent temperatures viz., 25 °C, 45 °C and 70 °C. Further, the effect of crosslinking, temperature and reaction time on catalytic activities of TRPUBs has been studied. TRPUBs grades have showna maximum swelling capacity up to 5200 %; excellent catalytic activity even at 70 °C; and 85 % activity retention after 18 days storage in buffer medium.

Cardiorespiratory consequences of attenuated fentanyl and augmented rocuronium dosing during protocolised prehospital emergency anaesthesia at a regional air ambulance service: a retrospective study.

BACKGROUND: Pre-Hospital Emergency Anaesthesia (PHEA) has undergone significant developments since its inception. However, optimal drug dosing remains a challenge for both medical and trauma patients. Many prehospital teams have adopted a drug regimen of 3 mcg/kg fentanyl, 2 mg/kg ketamine and 1 mg/kg rocuronium ('3:2:1'). At Essex and Herts Air Ambulance Trust (EHAAT) a new standard dosing regimen was introduced in August 2021: 1 mcg/kg fentanyl, 2 mg/kg ketamine and 2 mg/kg rocuronium (up to a maximum dose of 150 mg) ('1:2:2'). The aim of this study was to evaluate the cardiorespiratory consequences of a new attenuated fentanyl and augmented rocuronium dosing regimen. METHODS: A retrospective study was conducted at EHAAT as a service evaluation. Anonymized records were reviewed from an electronic database to compare the original ('3:2:1') drug dosing regimen (December 2019-July 2021) and the new ('1:2:2') dosing regimen (September 2021-May 2023). The primary outcome was the incidence of absolute hypotension within ten minutes of induction. Secondary outcomes included immediate hypertension, immediate hypoxia and first pass success (FPS) rates. RESULTS: Following exclusions (n = 121), 720 PHEA cases were analysed (360 new vs. 360 original, no statistically significant difference in demographics). There was no difference in the rate of absolute hypotension (24.4% '1:2:2' v 23.8% '3:2:1', p = 0.93). In trauma patients, there was an increased first pass success (FPS) rate with the new regimen (95.1% v 86.5%, p = 0.01) and a reduced incidence of immediate hypoxia (7.9% v 14.8%, p = 0.05). There was no increase in immediate hypertensive episodes (22.7% vs. 24.2%, p = 0.73). No safety concerns were identified. CONCLUSION: An attenuated fentanyl and augmented rocuronium dosing regimen showed no difference in absolute hypotensive episodes in a mixed cohort of medical and trauma patients. In trauma patients, the new regimen was associated with an increased FPS rate and reduced episodes of immediate hypoxia. Further research is required to understand the impact of such drug dosing in the most critically ill and injured subpopulation.

Metabolic engineering with adaptive laboratory evolution for phenylalanine production by Corynebacterium glutamicum.

The mutants resistant to a phenylalanine analog, 4-fluorophenylalanine (4FP), were obtained for metabolic engineering of Corynebacterium glutamicum for producing aromatic amino acids synthesized through the shikimate pathway by adaptive laboratory evolution. Culture experiments of the C. glutamicum strains which carry the mutations found in the open reading frame from the 4FP-resistant mutants revealed that the mutations in the open reading frames of aroG (NCgl2098), pheA (NCgl2799) and aroP (NCgl1062) encoding 3-deoxy-d-arabino-heptulosonate-7-phosphate, prephenate dehydratase, and aromatic amino acid transporter are responsible for 4FP resistance and higher concentration of aromatic amino acids in their culture supernatants in the 4FP-resistant strains. It was expected that aroG and pheA mutations would release feedback inhibition of the enzymes involved in the shikimate pathway by phenylalanine and that aroP mutations would prevent intracellular uptake of aromatic amino acids. Therefore, we conducted metabolic engineering of the C. glutamicum wild-type strain for aromatic amino acid production and found that phenylalanine production at 6.11 ± 0.08 g L-1 was achieved by overexpressing the mutant pheA and aroG genes from the 4FP-resistant mutants and deleting aroP gene. This study demonstrates that adaptive laboratory evolution is an effective way to obtain useful mutant genes related to production of target material and to establish metabolic engineering strategies.

Long-term in vivo degradation and biocompatibility of degradable pHEMA hydrogels containing graphene oxide.

Developing biocompatible, non-fouling and biodegradable hydrogels for blood-contacting devices remains a demanding challenge. Such materials should promote natural healing, prevent clotting, and undergo controlled degradation. This study evaluates the biocompatibility and biodegradation of degradable poly(2-hydroxyethyl methacrylate) (d-pHEMA) hydrogels with or without reinforcement with oxidized few-layer graphene (d-pHEMA/M5ox) in a long term implantation in rats, assessing non-desired side-effects (irritation, chronic toxicity, immune response). Subcutaneous implantation over 6 months revealed degradation of both hydrogels, despite slower for d-pHEMA/M5ox, with degradation products found in intracellular vesicles. No inflammation nor infection at implantation areas were observed, and no histopathological findings were detected in parenchymal organs. Immunohistochemistry confirmed d-pHEMA and d-pHEMA/M5ox highly anti-adhesiveness. Gene expression of macrophages markers revealed presence of both M1 and M2 macrophages at all timepoints. M1/M2 profile after 6 months reveals an anti-inflammatory environment, suggesting no chronic inflammation, as also demonstrated by cytokines (IL-α, TNF-α and IL-10) analysis. Overall, modification of pHEMA towards a degradable material was successfully achieved without evoking a loss of its inherent properties, specially its anti-adhesiveness and biocompatibility. Therefore, these hydrogels hold potential as blank-slate for further modifications that promote cellular adhesion/proliferation for tissue engineering applications, namely for designing blood contacting devices with different load bearing requirements. STATEMENT OF SIGNIFICANCE: Biocompatibility, tunable biodegradation kinetics, and suitable immune response with lack of chronic toxicity and irritation, are key features in degradable blood contact devices that demand long-term exposure. We herein evaluate the 6-month in vivo performance of a degradable and hemocompatible anti-adhesive hydrogel based in pHEMA, and its mechanically reinforced formulation with few-layer graphene oxide. This subcutaneous implantation in a rat model, shows gradual degradation with progressive changes in material morphology, and no evidence of local inflammation in surrounding tissue, neither signs of inflammation or adverse reactions in systemic organs, suggesting biocompatibility of degradation products. Such hydrogels exhibit great potential as a blank slate for tissue engineering applications, including for blood contact, where cues for specific cells can be incorporated.

Bioactive interpenetrating hybrids of poly(hydroxyethyl methacrylate-co-glycidyl methacrylate): Effect of polysaccharide types on structural peculiarities and multifunctionality.

Crosslinked poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) hybrids prepared in the same experimental condition by adding various polysaccharides of different chemical types; inulin, Na-alginate, starch and κ-Carrageenan were qualitatively compared. The results are presented to extract relevant physicochemical properties for qualitative comparison of structures within the same synthesis batch. Elastic properties and swelling degree of hybrids can be tightly regulated using different types of polysaccharides and by controlling effective cross-linking density. Addition of κ-Carrageenan to copolymer network increased elastic modulus by 6.2-fold in as-prepared state, but greatest increase in effective cross-link density through swelling was observed in alginate-doped gels. An overshooting effect was observed for alginate-doped hybrids; swelling first to a maximum, followed by a gradual deswelling until equilibrium was reached. Compressive elasticity of hybrids is mainly controlled by type of polysaccharides and cross-linking density but also depends on polymerization temperature. The obtained hybrid gels displayed excellent adsorption performance for methyl orange (MO). The highest adsorption capacity was reached with inulin-doped hybrids. The rate of adsorption was very fast and reached equilibrium with 98.9 % efficiency at about 90 min. This approach to modify the properties of hybrid gels with various types of polysaccharides may find wide use in biomaterials and water purification applications.

Regulating Electrostatic Interactions toward Thermoresponsive Hydrogels with Low Critical Solution Temperature.

Low critical solution temperature (LCST) of commonly used thermoresponsive polymers in water is basically dominated by hydrophobic interactions. Herein, a novel thermoresponsive system based on electrostatic interactions is reported. By simply loading aluminum chloride (AlCl3 ) into non-responsive poly(2-hydroxyethyl acrylate) (PHEA) hydrogels, PHEA-Al gels turn to have reversible thermoresponsive behavior between transparent and opaque without any volume change. Further investigations by changing metal ion-polymer compositions unravel the necessity of specific electrostatic interactions, namely, cation-dipole bonding interactions between hydroxy groups and trivalent metal ions. The thermoresponsive hydrogel demonstrates high transparency (≈95%), excellent luminous modulation capability (>98%), and cyclic reliability, suggesting great potential as an energy-saving material. Although LCST control by salt addition is widely known, salt-induced expression of thermoresponsiveness has barely been discussed before. This design provides a new approach of easy fabrication, low cost, and scalability to develop stimuli-responsive materials.

Enhanced invertase binding from baker's yeast via cryogels included boronic acids.

Invertase, an industrially significant glycoenzyme, was purified from baker's yeast using poly (2-Hydroxyethyl methacrylate) [PHema-Pba] cryogels functionalized with boronic acid. At subzero temperatures, PHema-Pba cryogels were synthesized and characterized using swelling tests, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The surface area of the PHema-Pba cryogels was 14 m2/g with a swelling ratio of 88.3% and macroporosity of 72%. The interconnected macropores of PHema-Pba cryogels were shown via scanning electron microscopy. Invertase binding capacity of PHema-Pba cryogel was evaluated by binding studies in different pH, temperature, and interaction time conditions and the maximum Invertase binding of PHema-Pba cryogel was found as 15.2 mg/g. and 23.7 fold Invertase purification was achieved from baker's yeast using PHema-Pba cryogels. The results show that PHema-Pba cryogels have high Invertase binding capacity and may be used as an alternative method for enzyme purification via boronate affinity systems.

Highly stretchable, self-healable and adhesive, thermal responsive conductive hydrogel loading nanocellulose complex for a flexible sensor.

Currently, with the widespread concerns of smart soft sensors in wearable electronics, human health detection and electronic skin, flexible conductive hydrogels have been extensively studied. However, it remains a great challenge to develop hydrogels that have both satisfactory mechanical performance with stretchable and compressible and high conductive. Herein, based on synergistic dynamic hydrogen and metal coordination bonds, polyvinyl alcohol (PVA)/poly (2-hydroxyethyl methacrylate) (PHEMA) hydrogels doped with polypyrrole decorated cellulose nanofibers (CNFs@PPy) are developed via free radical polymerization. The loading versatile CNFs@PPy highlighted the complex hydrogels super-stretchability (approximately 2600 % elongation) and excellent toughness (2.74 MJ/m3) properties to tensile deformation, strong compressive strength (1.96 MPa), fast temperature responsiveness and outstanding strain sensing capability (GF = 3.13). Moreover, the PHEMA/PVA/CNFs@PPy hydrogels possessed rapid self-healing and powerful adhesive abilities to various interfaces without extra assistance, as well as distinguished fatigue resistance performance. Such advantages make the nanocomposite hydrogel displayed high stability and repeatable to both pressure and strain in a wide range of deformations, enabling a promising candidate in the fields of motion monitoring and healthcare management.

Tailoring the Electron Trapping Effect of a Biocompatible Triboelectric Hydrogel by Graphene Oxide Incorporation towards Self-Powered Medical Electronics.

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact-separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 µA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA's triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 µA, and 1.28 W/m2 due to the observed increase in pHEMA's surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 µA, and 0.17 W/m2 less than pHEMA's. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from -7.3 to -0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA's matrix. All of the composites can charge a 10 µF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact-separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.

Poly(2-hydroxyethyl methacrylate) hydrogels containing graphene-based materials for blood-contacting applications: From soft inert to strong degradable material.

Degradable biomaterials for blood-contacting devices (BCDs) are associated with weak mechanical properties, high molecular weight of the degradation products and poor hemocompatibility. Herein, the inert and biocompatible FDA approved poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel was turned into a degradable material by incorporation of different amounts of a hydrolytically labile crosslinking agent, pentaerythritol tetrakis(3-mercaptopropionate). In situ addition of 1wt.% of oxidized graphene-based materials (GBMs) with different lateral sizes/thicknesses (single-layer graphene oxide and oxidized forms of few-layer graphene materials) was performed to enhance the mechanical properties of hydrogels. An ultimate tensile strength increasing up to 0.2 MPa (293% higher than degradable pHEMA) was obtained using oxidized few-layer graphene with 5 µm lateral size. Moreover, the incorporation of GBMs has demonstrated to simultaneously tune the degradation time, which ranged from 2 to 4 months. Notably, these features were achieved keeping not only the intrinsic properties of inert pHEMA regarding water uptake, wettability and cytocompatibility (short and long term), but also the non-fouling behavior towards human cells, platelets and bacteria. This new pHEMA hydrogel with degradation and biomechanical performance tuned by GBMs, can therefore be envisioned for different applications in tissue engineering, particularly for BCDs where non-fouling character is essential. STATEMENT OF SIGNIFICANCE: Suitable mechanical properties, low molecular weight of the degradation products and hemocompatibility are key features in degradable blood contacting devices (BCDs), and pave the way for significant improvement in the field. In here, a hydrogel with outstanding anti-adhesiveness (pHEMA) provides hemocompatibility, the presence of a degradable crosslinker provides degradability, and incorporation of graphene oxide reestablishes its strength, allowing tuning of both degradation and mechanical properties. Notably, these hydrogels simultaneously provide suitable water uptake, wettability, cytocompatibility (short and long term), no acute inflammatory response, and non-fouling behavior towards endothelial cells, platelets and bacteria. Such results highlight the potential of these hydrogels to be envisioned for applications in tissue engineered BCDs, namely as small diameter vascular grafts.

A Novel Antimicrobial Hydrogel for the Management of Periodontal Diseases.

OBJECTIVES: This study aimed to synthesise a drug-delivery system based on a porous polymer hydrogel, with antimicrobial properties against Porphyromonas gingivalis and potential to be used in tissue regeneration. MATERIAL AND METHODS: 2-Hydroxyethyl methacrylate monomers were polymerised using thermal and photoactivation in the presence of silver nitrate (AgNO3) and/or chlorhexidine digluconate. Poly-2-hydroxyethyl methacrylate (pHEMA) hydrogels containing silver nanoparticles (AgNPs) and/or 0.12% chlorhexidine (CHX) were produced and characterised using cryo-SEM and confocal microscopy. Hydrogel degradation and leaching of AgNP were tested for 1.5 months. The antimicrobial properties were tested against P. gingivalis using broth culture system and disk diffusion tests. RESULTS: Our methodology manufactured porous polymeric hydrogels doped with AgNPs and CHX. Hydrogels showed a successful delivery of CHX and sustainable release of AgNPs in a steady hydrogel degradation rate determined based on the weight loss of samples. Hydrogels with AgNPs or CHX had a significant antimicrobial effect against P. gingivalis, with CHX-hydrogels exhibiting a stronger effect than AgNP-hydrogels in the short-term assessment. AgNP-CHX hydrogels showed a compounded antimicrobial effect, whereas control hydrogels containing neither AgNPs nor CHX had no influence on bacterial growth (P < .05). CONCLUSIONS: The dual-cured pHEMA hydrogel loaded with antimicrobial agents proved to be an efficient drug-delivery system against periodontopathogens, with the potential to be used as a scaffold for tissue regeneration.

Green synthesis of quaternized chitosan nanogel using emulsion-photopolymerization as redox-responsive drug carrier.

We report the green synthesis of trimethyl chitosan-functionalized poly(2-hydroxyethyl methacrylate) (PHEMA-TMC) nanogels via surfactant-free emulsion photopolymerization. TMC, a quaternized derivative of chitosan, was synthesized through methylation of chitosan, resulting in quaternary and tertiary amine groups as the main substitution products. TMC tertiary amine moiety and riboflavin (RF) acted as a redox photo-initiating system to generate free radicals for the polymerization under light irradiation. The effects of polymerization parameters such as irradiation time, concentrations of TMC and RF were investigated using MBA as crosslinker. Under the optimal condition of 1 % TMC, 4 % HEMA, 0.8 µM RF, 5 % MBA, and 4 h of polymerization time, the cationic PHEMA-TMC nanogel was synthesized with 76 % monomer conversion and an average diameter of about 106 nm. Moreover, the disulfide-crosslinked PHEMA-TMC nanogel was also synthesized using the disulfide dimethacrylate crosslinker, which exhibited a redox-induced degradation and release of encapsulated melatonin, potentially useful as a redox-responsive drug delivery carrier.

Modeling of the PHEMA-gelatin scaffold enriched with graphene oxide utilizing finite element method for bone tissue engineering.

The development of computer-aided facilities has contributed to the optimization of tissue engineering techniques due to the reduction in necessary practical assessments and the removal of animal or human-related ethical issues. Herein, a bone scaffold based on poly (2-hydroxyethyl methacrylate) (PHEMA), gelatin and graphene oxide (GO), was simulated by SOLIDWORKS and ABAQUS under a normal compression force using finite element method (FEM). Concerning the mechanotransduction impact, GO could support the stability of the structure and reduce the possibility of the failure resulting in the integrity and durability of the scaffold efficiency which would be beneficial for osteogenic differentiation.

Molecularly Imprinted Cryogels for the Selective Adsorption of Salicylic Acid.

In this study, molecularly imprinted cryogels were fabricated for selective adsorption of salicylic acid. Cryogelation was performed at - 20 °C using a cationic monomer N,N-dimethylaminoethyl methacrylate as a functional monomer for salicylic acid. The morphology, swelling behaviors, and chemical structures of the cryogels were investigated. The general structure and porosities of cryogels were compared with the traditional hydrogels using field emission scanning electron microscopy (FE-SEM). The adsorption performance of cryogels toward salicylic acid was studied to investigate the optimal adsorption conditions. Adsorption capacity of the imprinted cryogels was 1.95 and 7.51 times higher than those of non-imprinted and bare PHEMA cryogels, respectively, due to the specific binding sites toward salicylic acid. Molecularly imprinted cryogels exhibited significant stability and reusability by keeping more than 85% of their adsorption capacity after ten regeneration cycles. Considering the fabrication process, adsorption capacity, selectivity, and reusability of the imprinted cryogels, these new materials could be utilized as a promising alternative for selective adsorption of drug molecules.

Synthesis and Properties of Polyol Copolymer with Alternating Methacrylate-Vinyl Ether Backbone.

Radical polymerization of a tailored diphenylsilane-bridged bi-functional monomer consisting of methacrylate and vinyl ether moieties is conducted in diluted monomer concentration, in which both two moieties are consumed at almost the same rate despite their huge difference in monomer reactivity ratio. The vinyl ether content in the backbone is quantified as 45% by 1 H NMR after removal of the silane bridge. Since vinyl ether alone cannot be polymerized in such radical polymerization, it should be incorporated in an alternating fashion with methacrylate into the copolymer main chain. The cleavage of silane bridge also yields a series of polyol materials composed of ethylene glycol monovinyl ether (EGVE) and hydroxyethyl methacrylate (HEMA), and the EGVE content in the backbone can be regulated from 45% to 18% by increasing the bi-functional monomer concentration. Interestingly, although containing more than 50% HEMA units, the alternating copolymer exhibits new properties totally different from poly(HEMA), but more similar to poly(EGVE), e.g., good water solubility and a markedly low glass transition temperature (Tg ) of -31 °C, which is attributed to the major HEMA-EGVE repeating unit that replaced HEMA-HEMA consecutive segments so that the properties of poly(HEMA) such as 95 °C Tg are completely altered.

A mechanically robust and stable estradiol-loaded PHEMA-based hydrogel barrier for intrauterine adhesion treatment.

Estrogen combined with physical barrier therapy may be a prospective method to repair a damaged endometrium and prevent postsurgical re-adhesion in the treatment of intrauterine adhesions (IUAs), but there lacks a suitable scaffold with good biocompatibility, appropriate mechanical properties, and drug-releasing kinetics. Herein, a mechanically robust and stable barrier based on the poly(hydroxyethyl methacrylate) (PHEMA) hydrogel combined with estradiol-loaded mesoporous silica is designed. The network is formed by covalent bonds and noncovalent coordination bonds, which endow the hydrogel with superior mechanical properties to most reported PHEMA-based hydrogels. Meanwhile, the covalent bonds impart excellent stability to the hydrogel, which maintains its structure and mechanical properties in a simulated uterine fluid for 30 days. The excellent mechanical properties and stability are comparable to those of a typical barrier material intrauterine device (IUD), enabling the hydrogel to be retained in the uterus and removed intact like an IUD. In vitro and in vivo experiments show that the hydrogel possesses good biocompatibility similar to pure PHEMA hydrogels. In addition, the hydrogel releases estradiol continuously and stably, and exhibits a good therapeutic effect in promoting the proliferation of endometrial cells and inhibiting the progression of fibrosis. Therefore, the combinational advantages make the present hydrogel very promising in IUA treatment.

Molecular dynamics study of the interactions between a hydrophilic polymer brush on graphene and amino acid side chain analogues in water.

We perform all-atom molecular dynamics simulations of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes in aqueous solutions of isobutane, propionamide, and sodium propionate. These solutes are side chain analogues to leucine, glutamine, and glutamic acid, respectively. We compute the Gibbs energy profile of the solute's adsorption to the polymer brush and decompose it into the contributions from the steric repulsion, van der Waals interaction, and Coulomb interaction to reveal the energetic origin of repulsion or attraction of the solute by the polymer brush. The Henry adsorption constant is the amount of adsorption normalized by the concentration in aqueous solution. We examine the dependence of this quantity on the grafting density and chain length. Our results suggest that the concurrent primary and ternary adsorption mechanism may be more important than previously expected when the solute is hydrophobic.

AFB1 recognition from liver tissue via AFB1 imprinted magnetic nanoparticles.

Aflatoxins (AFs) are produced mainly by Aspergillus flavus and Aspergillus parasiticus and aflatoxin B1 (AFB1) is one of the most toxic aflatoxins with its carcinogenic property. AFB1 recognition from samples is very important and PHEMA based AFB1 imprinted magnetic nanoparticles (magAFB1-MIPs) were synthesized for the selective AFB1 recognition from liver tissue. The AFB1-MIPs were synthesized in different mole ratios and NIPs were synthesized for control. Characterization studies of magAFB1-MIPs and NIPs were carried out by swelling tests, surface area measurements, scanning electron microscopy and particle size analysis. The surface area was found as 117 m2/g and the size of the nanoparticles were found as 483 nm in diameter. The percentage yield of polymerization was calculated as 98 % and the template (AFB1) removal ratio from the magAFB1-MIPs was calculated as 91 %. The maximum adsorbtion capacities were calculated as 427.57 ng g-1 for magAFB1-MIPs and 44.6 ng g-1 for magNIPs. Selectivity tests showed that magAFB1-MIPs adsorb AFB1 1.74, 4.40, 2.46 times selective than that of AFB2, AFG1 and AFG2 molecules, respectively. AFB1 removal amount from AFB1 spiked liver tissue was satisfactory and recorded as 10.4 ng g-1 and 54.8 ng g-1 for 2 ng g-1 and 10 ng g-1 spiked liver tissue samples, respectively. AFB1 adsorption amount decrease was found negligible for 10 consecutive adsorption-desorption repeats in reusability study.

Well-Defined pH-Responsive Self-Assembled Block Copolymers for the Effective Codelivery of Doxorubicin and Antisense Oligonucleotide to Breast Cancer Cells.

The worldwide steady increase in the number of cancer patients motivates the development of innovative drug delivery systems for combination therapy as an effective clinical modality for cancer treatment. Here, we explored a design concept based on poly(ethylene glycol)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate-formylbenzoic acid) [PEG-b-PDMAEMA-b-P(HEMA-FBA)] for the dual delivery of doxorubicin (DOX) and GTI2040 (an antisense oligonucleotide for ribonucleotide reductase inhibition) to MCF-7 breast cancer cells. PEG-b-PDMAEMA-b-PHEMA, the precursor copolymer, was prepared through chain extensions from a PEG-based macroinitiator via two consecutive atom transfer radical polymerization (ATRP) steps. Then, it was modified at the PHEMA block with 4-formylbenzoic acid (FBA) to install reactive aldehyde moieties. A pH-responsive polymer-drug conjugate (PDC) was obtained by conjugating DOX to the polymer structure via acid-labile imine linkages, and subsequently self-assembled in an aqueous solution to form DOX-loaded self-assembled nanoparticles (DOX-SAN) with a positively charged shell. DOX-SAN condensed readily with negatively charged GTI2040 to form GTI2040/DOX-SAN nanocomplexes. Gel-retardation assay confirmed the affinity between GTI2040 and DOX-SAN. The GTI2040/DOX-SAN nanocomplex at N/P ratio of 30 exhibited a volume-average hydrodynamic size of 136.4 nm and a zeta potential of 21.0 mV. The pH-sensitivity of DOX-SAN was confirmed by the DOX release study based on the significant cumulative DOX release at pH 5.5 relative to pH 7.4. Cellular uptake study demonstrated favorable accumulation of GTI2040/DOX-SAN inside MCF-7 cells compared with free GTI2040/DOX. In vitro cytotoxicity study indicated higher therapeutic efficacy of GTI2040/DOX-SAN relative to DOX-SAN alone because of the downregulation of the R2 protein of ribonucleotide reductase. These outcomes suggest that the self-assembled pH-responsive triblock copolymer is a promising platform for combination therapy, which may be more effective in combating cancer than individual therapies.