Acid Copolymer Research Articles

Preparation of Thifluzamide Polylactic Acid Glycolic Acid Copolymer Microspheres and Its Effect on the Growth of Cucumber Seedlings.

The polylactic acid-glycolic acid copolymer (PLGA) has been proven to be applicable in medicine, but there is limited research on its application and safety in the agricultural field. In this paper, thifluzamide PLGA microspheres were prepared via phacoemulsification and solvent volatilization, using the PLGA copolymer as the carrier and thifluzamide as the active component. It was found that the microspheres had good slow-release performance and fungicidal activity against Rhizoctonia solani. A comparative study was conducted to show the effect of thifluzamide PLGA microspheres on cucumber seedlings. Physiological and biochemical indexes of cucumber seedlings, including dry weight, root length, chlorophyll, protein, flavonoids, and total phenol content, indicated that the negative effect of thifluzamide on plant growth could be mitigated when it was wrapped in PLGA microspheres. This work explores the feasibility of PLGA as carriers in fungicide applications.

High Strength, Conductivity, and Bacteriostasis of the P(AM-co-AA)/Chitosan Quaternary Ammonium Salt Composite Hydrogel through Ionic Crosslinking and Hydrogen Bonding.

Traditional hydrogels with a single-crosslinked network structure suffer from poor stretchability, low sensitivity, and easy contamination, which seriously affect their practical application in the strain sensor field. To overcome these shortcomings, herein, a multiphysical crosslinking strategy (ionic crosslinking and hydrogen bonding) was designed to prepare a hydrogel strain sensor based on chitosan quaternary ammonium salt (HACC)-modified P(AM-co-AA) (acrylamide-co-acrylic acid copolymer) hydrogels. The ionic crosslinking for the double-network P(AM-co-AA)/HACC hydrogels was achieved by an immersion method with Fe3+ as crosslinking sites, which crosslinked with the amino group (-NH2) on HACC and the carboxyl group (-COOH) on P(AM-co-AA) and enabled the hydrogels to recover and reorganize rapidly, resulting in a hydrogel-based strain sensor with excellent tensile stress (3 MPa), elongation (1390%), elastic modulus (0.42 MPa), and toughness (25 MJ/m3). In addition, the prepared hydrogel exhibited high electrical conductivity (21.6 mS/cm) and sensitivity (GF = 5.02 at 0-20% strain, GF = 6.84 at 20-100% strain, and GF = 10.27 at 100-480% strain). Furthermore, the introduction of HACC endowed the hydrogel with excellent antibacterial properties (up to 99.5%) and excellent antibacterial activity against bacteria of three forms, bacilli, cocci, and spores. The flexible, conductive, and antibacterial hydrogel can be applied as a strain sensor for real-time detection of human motions such as joint movement, speech, and respiration, which exhibits a promising application prospect in wearable devices, soft robotic systems, and other fields.

A Study on the Thermal Degradation of an Acrylamide and 2-Acrylamido-2-Methylpropanesulfonic Acid Copolymer at High Temperatures.

As a temperature-resistant and salt-resistant polymer, acrylamide and 2-acrylamide-2-methylpropane sulfonic acid (abbreviated as AM-AMPS) copolymer is currently widely used in drilling, water control and oil production stabilization, enhanced oil recovery and other fields, but its stability under high temperature has been less studied. The degradation process of the AM-AMPS copolymer solution was studied by measuring viscosity, the degree of hydrolysis, and weight-average molecular weight at different temperatures and aging time. During the high-temperature aging process, the viscosity of the AM-AMPS copolymer saline solution first increases and then decreases. The combined action of the hydrolysis reaction and the oxidative thermal degradation leads to the change of the viscosity of the AM-AMPS copolymer saline solution. The hydrolysis reaction of the AM-AMPS copolymer mainly affects the structural viscosity of its saline solution through intramolecular and intermolecular electrostatic interactions, while the oxidative thermal degradation mainly reduces its molecular weight by breaking the main chain of the copolymer molecules, reducing the viscosity of the AM-AMPS copolymer saline solution. The content of AM and AMPS groups in the AM-AMPS copolymer solution at various temperatures and aging time was analyzed using liquid nuclear magnetic resonance carbon spectroscopy, demonstrating that the hydrolysis reaction rate constant of AM groups was significantly higher than that of AMPS groups. The contribution values of hydrolysis reaction and oxidative thermal degradation of the AM-AMPS copolymer at different aging time to viscosity were quantitatively calculated at temperatures ranging from 104.5 °C to 140 °C. It was determined that the higher the heat treatment temperature, the smaller the contribution of hydrolysis reaction to viscosity, while the bigger the contribution of oxidative thermal degradation to the viscosity of the AM-AMPS copolymer solution.

Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release

Recent work has highlighted that amorphous solid dispersions (ASDs) containing delamanid (DLM) and an enteric polymer, hypromellose phthalate (HPMCP), appear to be susceptible to crystallization during immersion in simulated gastric fluids. The goal of this study was to minimize contact of the ASD particles with the acidic media via application of an enteric coating to tablets containing the ASD intermediate, and improve the subsequent drug release at higher pH conditions. DLM ASDs were prepared with HPMCP and formulated into a tablet that was then coated with a methacrylic acid copolymer. Drug release was studied in vitro using a two-stage dissolution test where the pH of the gastric compartment was altered to reflect physiological variations. The medium was subsequently switched to simulated intestinal fluid. The gastric resistance time of the enteric coating was probed over the pH range of 1.6–5.0. The enteric coating was found to be effective at protecting the drug against crystallization in pH conditions where HPMCP was insoluble. Consequently, the variability in drug release following gastric immersion under pH conditions reflecting different prandial states was notably reduced when compared to the reference product. These findings support closer examination of the potential for drug crystallization from ASDs in the gastric environment where acid-insoluble polymers may be less effective as crystallization inhibitors. Further, addition of a protective enteric coating appears to provide a promising remediation strategy to prevent crystallization at low pH environments, and may mitigate variability associated with prandial state that arises due to pH changes.

Enhanced bone regeneration by low-intensity pulsed ultrasound and lipid microbubbles on PLGA/TCP 3D-printed scaffolds

BackgroundTo investigate the effect of low-intensity pulsed ultrasound (LIPUS) combined with lipid microbubbles on the proliferation and bone regeneration of bone marrow mesenchymal stem cells (BMSCs) in poly (lactic-glycolic acid copolymer) (PLGA)/α-tricalcium phosphate (TCP) 3D-printed scaffolds.MethodsBMSCs were irradiated with different LIPUS parameters and microbubble concentrations, and the best acoustic excitation parameters were selected. The expression of type I collagen and the activity of alkaline phosphatase were detected. Alizarin red staining was used to evaluate the calcium salt production during osteogenic differentiation.ResultsBMSCs proliferation was the most significant under the condition of 0.5% (v/v) lipid microbubble concentration, 2.0 MHz frequency, 0.3 W/cm2 sound intensity and 20% duty cycle. After 14 days, the type I collagen expression and alkaline phosphatase activity in the scaffold increased significantly compared to those in the control group, and alizarin red staining showed more calcium salt production during osteogenic differentiation. After 21 days, scanning electron microscopy experiments showed that osteogenesis was obvious in the PLGA/TCP scaffolds.ConclusionLIPUS combined with lipid microbubbles on PLGA/TCP scaffolds can promote BMSCs growth and bone differentiation, which is expected to provide a new and effective method for the treatment of bone regeneration in tissue engineering.

Sуnthesis of terpene–methacrylic acid copolymers and their effect on the stability of inorganic dispersions in the presence of cationic surfactants

Copolymers of methacrylic acid and natural terpene monomers (α-pinene; β-pinene; ∆3-karene) with the molecular weight of (0.3–0.5)∙104 and a content of carboxyl groups of 14.5–16.3 % were synthesized. For the synthesized copolymers, hydrodynamic radius and the Kuhn segment, which characterizes flexibility of a polymer chain, were determined, as well as the Huggins constant in aqueous and saline solutions, and concentration regions for formation of supramolecular structures. In the presence of a cationic surfactant (benzetonium chloride, Hyamine), depending on the concentration of copolymers in the system, polymer-surfactant complexes were formed in soluble and insoluble forms. It has been shown that the effectiveness of the stabilizing action of soluble complexes with respect to an aqueous dispersion of calcium carbonate increases with an increase in the content of nonpolar groups in the polymer chain. A cationic surfactant (Hyamine) has been proposed as a precipitant in the method for the quantitative determination of carboxyl-containing polymers in aqueous and saline media.

Thermogravimetric, Morphological and Infrared Analysis of Blends Involving Thermoplastic Starch and Poly(ethylene-co-methacrylic acid) and Its Ionomer Form.

This study focuses on the thermal properties and structural features of blends consisting of thermoplastic starch (TPS) and poly(ethylene-co-methacrylic acid) copolymer (EMAA) or its ionomer form (EMAA-54Na). The aim is to investigate how carboxylate functional groups of the ionomer form intervene in blends compatibility at the interface of the two materials and how this impacts their properties. Two series of blends (TPS/EMAA and TPS/EMAA-54Na) were produced with an internal mixer, with TPS compositions between 5 and 90 wt%. Thermogravimetry shows two main weight losses, indicating that TPS and the two copolymers are primarily immiscible. However, a small weight loss existing at intermediate degradation temperature between those of the two pristine components reveals specific interactions at the interface. At a mesoscale level, scanning electron microscopy confirmed thermogravimetry results and showed a two-phase domain morphology, with a phase inversion at around 80 wt% TPS, but also revealed a different surface appearance evolution between the two series. Fourier-transformed infrared spectroscopy analysis also revealed discrepancies in fingerprint between the two series of blends, analysed in terms of additional interactions in TPS/EMAA-54Na coming from the supplementary sodium neutralized carboxylate functions of the ionomer.

Preparation of Bismuth Tungstate/Preoxidized Acrylonitrile/Acrylic Acid Copolymer Composite Nanofiber Membrane and Its Photocatalytic Properties.

In this patent article, a novel bismuth tungstate/preoxidized acrylonitrile/ acrylic acid (AN/AA) copolymer composite nanofiber membrane was prepared, which was used as the visible light catalyst. AN/AA copolymer was synthesized, which was electrospun with bismuth nitrate and sodium tungstate to prepare the composite nanofiber. Then the composite nanofiber was preoxidized to prepare the bismuth tungstate/preoxidized AN/AA composite nanofiber membrane containing adsorption moiety and photocatalytic active moiety. The photocatalytic activity of bismuth tungstate/preoxidized AN/AA composite nanofiber membrane with different preoxidized temperature, heating rate, and holding time by catalytic degradation of methylene blue was investigated. The optimal preoxidized conditions were as follows: the preoxidized temperature was heated to 200 °C with the heating rate of 1°C/min and the holding time at this temperature was 12 h. The chemical structure and morphology of the composite nanofiber membrane were characterized by FTIR, XRD, and SEM. The bismuth tungstate/preoxidized AN/AA composite nanofiber membrane obtained good photocatalytic properties and reusability under visible light. The degradation rate of methylene blue by this visible light catalyst could reach 90.24% for 4.5 h, and the degradation rate remained 81.53% for 4.5 h after 5 reuses.

Encapsulation of Neem oil from Azadirachta indica into Poly (lactic-co-glycolic acid) as a novel sprayable miticide system with long-term storage stability and controlled release kinetic

In this study, Neem oil (NO) was extracted from the seeds of Azadirachta indica as a natural miticide agent. To prolong the insecticidal activity and control the sustainable release, various concentrations of NO were encapsulated in poly(D, L-lactic-co-glycolic) acid (PLGA) copolymers and high and low molecular weight (Mw) polyvinyl alcohol (PVAH and PVAL) microparticles (MPs) using the single and double emulsion solvent evaporation method. The effects of different parameters, such as the molecular weight of the stabilizing agent (PVA), stirring time, and polymer concentrations, on the size, stability, morphology, encapsulation efficiency, and release kinetics of the MPs were investigated. The presence of NO in PLGA/PVA MPs was confirmed by a shift in the glass transition temperature (Tg) to lower temperatures in the DSC thermograph, the appearance of peaks at 2854 cm−1 in the FTIR spectrum, a peak at 205 nm in the UV–vis spectrum and a rough surface in SEM. Moreover, the release kinetics of the MPs demonstrated sustained release of NO over 48 h. In terms of MPs storage, temperature affected short-term stability, while long-term stability after one year in a dark environment at room temperature was confirmed by the particles' strength. The miticide assay on dust mites Dermatophagoides pteronyssinus revealed that MPs with the highest NO concentration (PLGA/PVAL/NO 65%) exhibited the most effective miticidal activity, achieving a 100% kill rate after 24 h. Finally, the colloidal dispersion and stability of the MPs over time were assessed using rheology, and the results confirmed the particles' spray ability for miticide application.

Development and evaluation of cell membrane-based biomimetic nanoparticles loaded by Clostridium perfringens epsilon toxin: a novel vaccine delivery platform for Clostridial-associated diseases

As Clostridium perfringens (C. perfringens) epsilon toxin (ETX) ranks as the third most potent clostridial toxin after botulinum and tetanus toxins, vaccination is necessary for creatures that can be affected by it to be safe from the effects of this toxin. Nowadays, nanostructures are good choices for carriers for biological environments. We aimed to synthesize biomimetic biodegradable nanodevices to enhance the efficiency of the ETX vaccine. For this purpose, poly(lactic-co-glycolic acid) (PLGA) copolymer loaded with purified epsilon protoxin (proETX) to create nanoparticles called nanotoxins (NTs) and then coated by RBC membrane-derived vesicles (RVs) to form epsilon nanotoxoids (RV-NTs). The resulting RV-NTs shaped smooth spherical surfaces with double-layer core/shell structure with an average particle size of 105.9 ± 35.1 nm and encapsulation efficiency of 97.5% ± 0.13%. Compared with NTs, the RV-NTs were more stable for 15 consecutive days. In addition, although both structures showed a long-term cumulative release, the release rates from RV-NTs were slower than NTs during 144 hours. According to the results of cell viability, ETX loading in PLGA and entrapment in the RBC membrane decreased the toxicity of the toxin. The presence of PLGA enhances the uptake of proETX, and the synthesized structures showed no significant lesion after injection. These results demonstrate that NTs and RV-NTs could serve as an effective vaccine platform to deliver ETX for future in vivo assays.

Peptide-modified bioresponsive chondroitin sulfate micelles for targeted doxorubicin delivery in triple-negative breast cancer

Triple-negative breast cancer is an offensive tumor that is highly challenging to cure. In this study, we developed novel polymeric nanoparticles that target dual receptors and respond to reducing conditions for chemotherapeutic drug release in the treatment of triple-negative breast cancer. Then we synthesized and characterized a targeted peptide-grafted chondroitin sulfate A-ss-deoxycholic acid (TCSSD) copolymer and prepare doxorubicin (DOX)-loaded TCSSD (TCSSD-D) micelles high-loading content. The bioresponsive drug release of TCSSD-D nanoparticles was demonstrated in a glutathione-containing phosphate buffer solution. We found that TCSSD-D effectively targeted CD44 and P-selectin receptors both in vitro and in vivo. TCSSD-D micelles were higher cytotoxicity and cellular uptake than unmodified DOX-containing micelles in MDA-MB-231 cells. Furthermore, TCSSD-D micelles showed the strongest suppression of tumor growth among three DOX-based formulations in triple-negative MDA-MB-231-bearing nude mice. These results suggest that amphiphilic TCSSD nanoparticles can serve as a targeted and intelligent delivery vehicle for triple-negative breast cancer therapy.

Dox-loaded TPU-PLGA nanoparticles embedded chitosan hydrogel formulation as an effective anti-cancer therapy

Recently, Polylactic-co-glycolic acid (PLGA)-based polymeric nanosystems are gaining a lot of attention as drug carriers for cancer treatment. However, the degradation of PLGA-based systems through bulk erosion induces systemic toxicity and is quite unfavorable, thus signifying the need for a controlled drug release system. In this perspective, the present study involves the synthesis of a novel thermoplastic polyurethane-polylactic-co-glycolic acid (TPU-PLGA) copolymer. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to characterize the synthesized copolymer. The novel copolymer was further evaluated for encapsulation of the anticancer drug doxorubicin (Dox). To facilitate more sustained drug delivery, Dox-loaded TPU-PLGA nanoparticles (TPU-PLGA-Dox NPs) were embedded in a chitosan (CTP-Dox NPs) hydrogel which protected the embedded NPs and aided in additional engineering flexibility. Also, the drug release profiles showed stable and pH-responsive drug release from the CTP-Dox NPs based-hydrogel reservoir system. Furthermore, the cell viability assay and internalization studies were performed for the CTP-Dox NPs hydrogel along with native Dox and TPU-PLGA-Dox NPs. The novel CTP-Dox NPs hydrogel system has a lot of potential for improving the overall therapeutic performance of anti-cancer treatments by prolonging the sustained release of the drug.

Advanced treatment of low-pollution and poor biodegradability sewage by combined process

A system was developed for the treatment of low-pollution sewage with poor biodegradability and a low ratio of chemical oxygen demand (CODCr) to nitrate-nitrogen (COD/NO3−-N (C/N)) ratio to achieve high efficiency. This system combines the anaerobic-oxic (AO) process with the biological aerated filter (BAF) and introduces the Fenton advanced oxidation process. A pilot test system was established, and feasibility investigations were conducted using a continuous flow of 500 L/h. The results showed that the optimal conditions for removing nitrate from sewage were achieved with a C/N ratio of 5.5–6 and a hydraulic retention time (HRT) of 4 h. Under these conditions, the average nitrate removal efficiency was 83.36%, and the average concentration of total nitrogen (TN) in the effluent was reduced to 6.68 mg/L. Additionally, the Fenton oxidation treatment was effective in reducing the COD content of sewage, with an average removal efficiency of 82.47% and a decrease in CODCr from 55.24 mg/L to 9.68 mg/L. The combined process successfully met the stringent discharge standards after advanced treatment. Microbial community analysis revealed that the dominant genera in anoxic BAFs were Trichococcus, Comamonadaceae, Lentimicrobium, and Thauera, while the dominant genera in aerobic BAFs were mainly Acinetobacter, Thiothrix, Gemmobacter, and Caldilineaceae. The synergistic effect of various nitrifying and denitrifying bacteria in BAFs effectively removed nitrate from the sewage. Furthermore, GC-MS analysis indicated that the Fenton oxidation significantly reduced the concentration of refractory organic compounds in the sewage, including long-chain organic compounds and acrylic acid maleic acid copolymer (MA/AA). After upgrading and renovating the factory's sewage treatment facilities, the impact of the discharged effluent on the receiving drainage basin will be minimized.

Synthesis of poly(citric acid–aspartic acid) copolymer for efficient inhibition of shale hydration in water-based drilling fluids

Poly (citric acid–aspartic acid) copolymer was synthesized and assessed as a shale hydration inhibitor. The formation of the biomass-based eco-friendly copolymer was verified using Fourier transform infrared spectroscopy, and the structure confirmed by 13C and 1H nuclear magnetic resonance. Thermal degradation of the copolymer was evaluated by thermogravimetric analysis, which suggested that the copolymer has outstanding stability. Characterization using scanning electron microscopy, equipped with an energy-dispersive X-ray spectrometer, was carried out to confirm the shale morphology before and after copolymer treatment. Shale recovery tests, immersion experiments, and anti-swelling measurements were performed to determine inhibitor performance in the drilling process. The copolymer showed the highest shale dispersion recovery compared to a commonly used inhibitor (potassium chloride) and water. The anti-swelling and immersion results indicated that the copolymer was strongly adsorbed over the clay's surface through hydrogen bonding and electrostatic interaction. Consequently, clay hydrophobicity could be increased by producing a hydrophobic film on its surface, which would decrease the number of hydrogen bonds between shale and water, hence reducing the quantity of water invasion.

Combined chemo and photo therapy of programmable prodrug carriers to overcome delivery barriers against nasopharyngeal carcinoma

Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.

Development of Synthetic Polymer-based Nanomachine for Cancer Diagnosis and Therapy

This paper introduces the research of nanomachines utilizing boron chemistry. Boron neutron capture therapy (BNCT) has beeing attracting increasing attention as a minimally invasive cancer treatment, and p-boronophenylalanine (BPA) has been approved as a potent BNCT drug. However, intratumoral retention of BPA remains to be improved. Recently, we have developed a BPA delivery system [poly vinyl alcohol (PVA)-BPA] utilizing PVA. PVA-BPA altered the uptake pathway of BPA by cancer cells and significantly improved the intracellular retention in cancer cells. in the in vivo experiments, PVA-BPA showed improved tumor accumulation and a remarkable tumor growth inhibition upon thermal neutron irradiation. On the other hand, a useful delivery system of bioactive proteins has been strongly demanded. In this study, we have developed the ternary complex micelles for the protein delivery utilizing tannic acid (TA) and block copolymer containing a boronic acid group. The ternary micelles improved the blood retention and tumor accumulation of the loaded proteins, and realized a tumor tissue-selective enzymatic reaction in the enzyme delivery.

Repolarization of macrophages to improve sorafenib sensitivity for combination cancer therapy.

Sorafenib is the first line drug for hepatocellular carcinoma (HCC) therapy. However, HCC patients usually acquire resistance to sorafenib treatment within 6 months. Recent evidences have shown that anticancer drugs with antiangiogenesis effect (e.g., sorafenib) can aggravate the hypoxia microenvironment and promote the infiltration of more tumor-associated macrophages (TAMs) into the tumor tissues. Therefore, repolarization of TAMs phenotype could be expected to not only eliminate the influence of TAMs on sorafenib lethality to HCC cells, but also provide an additional anticancer effect to achieve combination therapy. However, immune side effects remain a great challenge due to the non-specific macrophage repolarization in normal tissues. We herein employed a tumor microenvironment (TME) pH-responsive nanoplatform to concurrently transport sorafenib and modified resiquimod (R848-C16). This nanoparticle (NP) platform is made with a TME pH-responsive methoxyl-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymer. After intravenous administration, the co-delivery NPs could highly accumulate in the tumor tissues and then respond to the TME pH to detach their surface PEG chains. With this PEG detachment to enhance uptake by TAMs and HCC cells, the co-delivery NPs could combinatorially inhibit HCC tumor growth via sorafenib-mediated lethality to HCC cells and R848-mediated repolarization of TAMs into tumoricidal M1-like macrophages. STATEMENT OF SIGNIFICANCE: Anticancer drugs with antiangiogenesis effect (e.g., sorafenib) can aggravate the hypoxia microenvironment and promote the infiltration of more tumor-associated macrophages (TAMs) into the tumor tissues to restrict the anticancer effect. In this work, we designed and developed a tumor microenvironment (TME) pH-responsive nanoplatform for systemic co-delivery of sorafenib and resiquimod in hepatocellular carcinoma (HCC) therapy. These co-delivery NPs show high tumor accumulation and could respond to the TME pH to enhance uptake by TAMs and HCC cells. With the sorafenib-mediated lethality to HCC cells and R848-mediated repolarization of TAMs, the co-delivery NPs show a combinational inhibition of HCC tumor growth in both xenograft and orthotopic tumor models.

Influence of talc and hydrogenated castor oil on the dissolution behavior of metformin-loaded pellets with acrylic-based sustained release coating

Multi-unit pellet system (MUPS) is of great interest as it is amenable to customization. MUPS comprises multi-particulates, usually as pellets or spheroids, which can be coated with diffusion barrier coatings. One commonly used diffusion barrier coating is the methacrylic acid copolymer, which can be used as a taste masking, enteric or sustained release polymer. While the versatility of methacrylic acid copolymers makes them pliable for pellet coating, there are impediments associated with their use. Additives commonly required with this polymer, including plasticizer and anti-adherent, have been shown to weaken the film strength. The objective of this study was to investigate the impact of osmotic pressure within the core on the sustained release coat integrity and functionality. Hydrogenated castor oil (HCO) was chosen as the additive to be studied. Metformin-loaded pellets, prepared via extrusion-spheronization, were coated with ethyl acrylate and methyl methacrylate copolymer (Eudragit RS 30 D) containing talc, talc-HCO, or HCO to different coat thicknesses. Drug release was investigated using the USP dissolution apparatus 2 and an ultraviolet imager. The swelling of the pellets when wetted was monitored by video imaging through a microscope. When coated to 7.5 % coat weight gain, coats with HCO slowed down drug release more than the other pellets. The pellets also swelled the most, which suggests that they were more resistant to the osmotic pressure exerted by metformin. For drugs which exert high osmotic pressure, HCO can serve as an efficient alternative to talc in the preparation of methacrylic acid copolymer coatings.

Chiral Polymer Micelles Alleviate Adriamycin Cardiotoxicity via Iron Chelation and Ferroptosis Inhibition

AbstractThe dose‐dependent cardiomyopathy of adriamycin (doxorubicin) limits its long‐term clinical use, which is revealed as a consequence of cardiomyocyte ferroptosis. As a ferrous iron (Fe2+)‐dependent regulated cell death pathway, ferroptosis is induced by the tailored lipid peroxides in the cell membranes. Herein, iron‐chelating polymer micelles are reported for concurrent doxorubicin delivery and cardiotoxicity reduction. The amphiphilic polymer consists of methoxy poly (ethylene glycol)‐co‐poly (glutamic acid) copolymer as the backbone and deferiprone analog as the side chain. The chiral polymer adopted the α‐helix conformation to enable prolonged retention in the cell membranes, resulting in efficient iron chelation, ferroptosis inhibition, and cardiotoxicity reduction. The co‐encapsulation of doxorubicin and coenzyme Q10 (CoQ10) in micelles further alleviates the cardiotoxicity because the reduced CoQ10 can act as a radical trapping agent to constrain lipid peroxidation and cardiomyocyte ferroptosis. The reduction of cardiotoxicity is accompanied by enhanced anticancer efficacy in an in vivo murine breast cancer model. The chiral iron‐chelating polymer micelles can be a promising platform for enhanced doxorubicin delivery and reduced cardiac adverse effects.

A generalizable protocol for expression and purification of membrane-bound bacterial phosphoglycosyl transferases in liponanoparticles

Phosphoglycosyl transferases (PGTs) are among the first membrane-bound enzymes involved in the biosynthesis of bacterial glycoconjugates. Robust expression and purification protocols for an abundant subfamily of PGTs remains lacking. Recent advancements in detergent-free methods for membrane protein solubilization open the door for purification of difficult membrane proteins directly from cell membranes into native-like liponanoparticles. By leveraging autoinduction, in vivo SUMO tag cleavage, styrene maleic acid co-polymer liponanoparticles (SMALPs), and Strep-Tag purification, we have established a robust workflow for expression and purification of previously unobtainable PGTs. The material generated from this workflow is extremely pure and can be directly visualized by Cryogenic Electron Microscopy (CryoEM). The methods presented here promise to be generalizable to additional membrane proteins recombinantly expressed in E. coli and should be of interest to the greater membrane proteomics community.