Biodegradable Poly Research Articles

Molybdenum temporary epicardial pacing wires: function and biodegradation

Abstract Cardiac pacing with temporary epicardial pacing wires (TEPW) is used to treat rhythm disturbances after cardiac surgery. Wires typically begin to fail around postoperative day four and are extracted. Occasionally, TEPW cannot be mechanically removed, have to stay in the thorax and may rarely cause serious complications like migration and infection. We aim to develop novel, bioresorbable TEPW which will dissolve over time, even if postoperative removal is unsuccessful. We manufactured prototypical braided molybdenum (Mo) leads (16 Mo wires of 40 µM diameter each, length 18 cm for ex vivo, 7.5 cm for in vivo experiments) coated with the biodegradable polymers poly(lactide-co-glycolic acid) (PLGA, inner coating) and polycaprolactone (PCL, outer coating) for shaping and electrical insulation. Mo electrodes showed similar pacing and sensing properties to conventional steel electrodes (Osypka) in Langendorff-perfused rat hearts, even with somewhat lower stimulation thresholds. In artificial body fluid at 37°C, the polymer-coated Mo electrodes dissolved at a rate of 1.6 ± 0.3 µg/cm2·d (n = 5) compared to uncoated electrodes with 30.3 ± 0.8 µg/cm2·d (n = 4, p < 0.001). Assessing apoptosis and necrosis in human cardiomyocytes and cardiac fibroblasts, we detected no toxicity at Mo concentrations up to 0.52 mM. To test the in vivo properties of Mo TEPW, we sutured them epicardially onto the anterior wall of the heart of female Wistar rats, led them out of the thorax through an intercostal space and placed them in a subcutaneous pocket. We tested electrophysiological properties directly after implantation and after different time periods. Mo TEPW showed similar pacing and sensing properties directly upon implantation and after 2 weeks, with only impedance and slew rate of the sensed R-wave decreasing time-dependently. After one month, all but one pair of Mo electrodes were mechanically broken at their exit from the thorax, the site of assumedly highest mechanical stress. Progressive Mo degradation led to multiple fragmentation of the Mo TEPW after 6 months. The conventional steel TEPW we used as control had similar electrical properties directly after implantation, after 2 weeks and one month without signs of broken electrodes. After 6 months, all but one pair of steel electrodes were mechanically broken at their thorax exit site. Comparing urinary Mo concentration of Mo TEPW treated rats to controls, we saw similar values of 1.9 ± 1.9 µM (n = 6) vs. 0.6 ± 0.2 µM (n = 5, n.s.) after one week. In contrast, we saw a significant increase of 12.1 ± 9.7 µM (n = 5) vs. 1.0 ± 0.9 µM (n = 5, p < 0.001) after 6 months, reflecting the degradation progress. We demonstrate that Mo TEPW are a feasible option for epicardial pacing in vivo for up to 2 weeks and observed the progress of Mo degradation up to 6 months. These findings represent an important step in the development of bioresorbable TEPW as a novel and even safer approach to temporary epicardial pacing.Graphical AbstractIn Vivo Degradation Progress

Unveiling the influence of oxygen on drug release dynamics in semipermeable polymersomes.

Semipermeable polymersomes, a class of polymeric vesicles that allow molecular passage across their membranes, offer significant potential for controlled drug delivery. These vesicles can be designed for inherent or selective permeability through the choice of suitable copolymers or the incorporation of protein nanopores, respectively. In this study, we explore a novel approach using oxygen-producing enzymatic reactions within biodegradable poly(ethylene glycol)-poly(caprolactone-gradient-trimethylene carbonate) (PEG-p(CL-g-TMC)) polymersomes to modulate drug release. These polymersomes were found to enhance the release of hydrophobic drugs while retaining hydrophilic drugs. The enzymatic generation of oxygen within the polymersomes increased membrane hydrophobicity, influencing drug release kinetics. The findings highlight the importance of understanding drug release kinetics in designing effective drug delivery systems, as the release rate and mechanism critically impact therapeutic efficacy and patient outcomes.

Medical- and Non-Medical-Grade Polycaprolactone Mesh Printing for Prolapse Repair: Establishment of Melt Electrowriting Prototype Parameters

Pelvic organ prolapse (POP) occurs due to inadequate support of female pelvic organs and is often treated with synthetic implants. However, complications like infections, mesh shrinkage, and tissue erosion can arise due to biomechanical incompatibilities with native tissue. This study aimed to optimize the melt electrowriting process using medical-grade biodegradable Poly(ε-caprolactone) (PCL) with a pellet extruder to print meshes that mimic the mechanical properties of vaginal tissue. Square and diagonal mesh designs with filament diameters of 80 µm, 160 µm, and 240 µm were produced and evaluated through mechanical testing, comparing them to a commercial mesh and sheep vaginal tissue. The results showed that when comparing medical-grade with non-medical-grade square meshes, there was a 54% difference in the Secant modulus, with the non-medical-grade meshes falling short of matching the properties of vaginal tissue. The square-shaped medical-grade PCL mesh closely approximated vaginal tissue, showing only a 13.7% higher Secant modulus and a maximum stress of 0.29 MPa, indicating strong performance. Although the diagonal-shaped mesh exhibited a 14% stress difference, its larger Secant modulus discrepancy of 45% rendered it less suitable. In contrast, the commercial mesh was significantly stiffer, measuring 77.5% higher than vaginal tissue. The diagonal-shaped mesh may better match the stress–strain characteristics of vaginal tissue, but the square-shaped mesh offers stronger support due to its higher stress–strain curve. Overall, meshes printed with medical-grade PCL show superior performance compared to non-medical-grade meshes, suggesting that they are a promising avenue for future advancements in the field of POP repair.

How the Aliphatic Glycol Chain Length Determines the Pseudoeutectic Composition in Biodegradable Isodimorphic poly(alkylene succinate-ran-caprolactone) Random Copolyesters.

We synthesize four series of novel biodegradable poly(alkylene succinate-ran-caprolactone) random copolyesters using a two-step ring-opening/transesterification and polycondensation process with ε-caprolactone (PCL) as a common comonomer. The second comonomers are succinic acid derivatives, with variations in the number of methylene groups (nCH2) in the glycol segment, nCH2 = 2, 4, 8, and 12. The obtained copolyesters were poly(ethylene succinate-ran-PCL) (ESxCLy), poly(butylene succinate-ran-PCL) (BSxCLy), poly(octamethylene succinate-ran-PCL) (OSxCLy), and poly(dodecylene succinate-ran-PCL) (DSxCLy). We discovered a new mixed isodimorphic/comonomer exclusion crystallization in ESxCLy copolymers. The BSxCLy, OSxCLy, and DSxCLy copolymers display isodimorphic behavior. Our findings revealed a significant variation in the pseudoeutectic point position, from mixed isodimorphism/comonomer exclusion crystallization to isodimorphism with pseudoeutectic point variation from 54% to up to 90%. Moreover, we established a link between the melting temperature depression slope variation and the comonomer inclusion/exclusion balance, providing valuable insights into the complex topic of isodimorphic random copolymers.

Melt Polycondensation Strategy to Access Unexplored l-Amino Acid and Sugar Copolymers.

Biodegradable polymers from bioresources are highly in demand for the development of sustainable polymer platforms for commodity plastics and in the biomedical field. Here, an elegant one-pot synthetic strategy is developed, for the first time, to access unexplored hybrid polymers from two naturally abundant resources: carbohydrates (sugars) and l-amino acids. A bottleneck in the synthetic strategy is overcome by tailor-making d-mannitol-based six- and five-membered bicyclic acetalized diols, and their structures are confirmed by single-crystal X-ray diffraction and 2D NMR spectroscopy. l-Amino acids are converted into ester-urethane functional monomers, and they are polymerized with sugar-diols under solvent-free melt polycondensation to yield biodegradable poly(ester-urethane)s. Acid-catalyzed deprotection yielded amphiphilic polymers having exclusively alternating residues of sugar and l-amino acid in the polymer backbone. The polymer is self-assembled into 200 ± 10 nm sized nanoparticles that can encapsulate fluorescent dyes, are nontoxic to cells up to 250 μg/mL, and are readily endocytosed for lysosomal enzymatic biodegradation at the cellular level.

Targeted PHA Microsphere-Loaded Triple-Drug System with Sustained Drug Release for Synergistic Chemotherapy and Gene Therapy.

The combination of paclitaxel (PTX) with other chemotherapy drugs (e.g., gemcitabine, GEM) or genetic drugs (e.g., siRNA) has been shown to enhance therapeutic efficacy against tumors, reduce individual drug dosages, and prevent drug resistance associated with single-drug treatments. However, the varying solubility of chemotherapy drugs and genetic drugs presents a challenge in co-delivering these agents. In this study, nanoparticles loaded with PTX were prepared using the biodegradable polymer material poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx). These nanoparticles were surface-modified with target proteins (Affibody molecules) and RALA cationic peptides to create core-shell structured microspheres with targeted and cationic functionalization. A three-drug co-delivery system (PTX@PHBHHx-ARP/siRNAGEM) were developed by electrostatically adsorbing siRNA chains containing GEM onto the microsphere surface. The encapsulation efficiency of PTX in the nanodrug was found to be 81.02%, with a drug loading of 5.09%. The chemogene adsorption capacity of siRNAGEM was determined to be 97.3%. Morphological and size characterization of the nanodrug revealed that PTX@PHBHHx-ARP/siRNAGEM is a rough-surfaced microsphere with a particle size of approximately 150 nm. This nanodrug exhibited targeting capabilities toward BT474 cells with HER2 overexpression while showing limited targeting ability toward MCF-7 cells with low HER2 expression. Results from the MTT assay demonstrated that PTX@PHBHHx-ARP/siRNAGEM exhibits high cytotoxicity and excellent combination therapy efficacy compared to physically mixed PTX/GEM/siRNA. Additionally, Western blot analysis confirmed that siRNA-mediated reduction of Bcl-2 expression significantly enhanced cell apoptosis mediated by PTX or GEM in tumor cells, thereby increasing cell sensitivity to PTX and GEM. This study presents a novel targeted nanosystem for the co-delivery of chemotherapy drugs and genetic drugs.

IN VIVO APPLICATION OF LOCAL DRUG DELIVERY SYSTEMS AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL/TERATOID/RHABOID TUMOURS

Abstract AIMS Local drug delivery systems (LDDSs) applied during neurosurgery offer a means of overcoming poor blood brain barrier (BBB) permeability and have been extensively investigated for the treatment of adult gliomas, but to the best of our knowledge, not for the treatment of paediatric cerebellar tumours. Here we report the applicability of an LDDS against medulloblastoma group 3 (MB3) and atypical teratoid/rhaboid tumours (AT/RT), both of which are associated with poor prognoses. METHOD We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)- poly(ethyleneglycol) (PECE) hydrogel, which has been investigated with an array of therapeutic agents against numerous cancer types. Here, we loaded the PECE hydrogel with chemotherapeutics previously identified as being effective against primary MB3 and AT/RT in vitro, but which do not cross the BBB in vivo, namely CHIR99021, ribavirin and PG545. Biocompatibility and cytotoxicity of drug loaded hydrogels was assessed in vitro. LDDSs safety and efficacy was evaluated using patient derived MB3 and AT/RT intracranial xenograft surgical resection models. RESULTS The hydrogel was both biocompatible and effected cytotoxicity following drug release. In vivo efficacy experiments against MB3 indicated a comparable median survival in treatment arms receiving radiotherapy or CHIR99021 and PG545 loaded LDDS. However, combined radiotherapy and LDDS conferred a significant survival enhancement, including long-term survivors. Against AT/RT, the median survival of arms receiving radiotherapy was comparable to that of the CHIR99021 and ribavirin loaded LDDS, with long-term survivors observed only in the latter arm. CONCLUSION The application of LDDSs against cerebellar brain tumours offers a promising novel therapeutic alternative. For MB3, the combination of radiotherapy and a LDDS significantly enhances survival compared to radiotherapy alone. For AT/RT, the comparable survival of the LDDS and radiotherapy alone is encouraging and indicates the possibility of circumventing radiation-induced adverse effects for young children impacted by this disease.

High-performance biodegradable triboelectric nanogenerators using CoFe2O4 filled poly (butylene adipate-co-terephthalate)

The hunt for sustainable and efficient energy harvesting and storage devices has driven significant interest in triboelectric nanogenerators (TENGs) as potential alternatives to traditional batteries for powering electronic devices. However, the development of biodegradable TENGs remains a formidable challenge. This study presents the preparation of a tribopositive material entirely composed of biodegradable poly(butylene adipate-co-terephthalate) (PBAT) polymer enhanced with CoFe2O4 (CF) nanoparticles. The CF nanoparticles, synthesized via the combustion method, were incorporated into the PBAT matrix through solvent casting to form films with varied filler content (0.2, 0.4, 0.6, 0.8, and 1 g). The CF nanoparticles structural, surface, and electrical properties were characterized using XRD and FTIR spectroscopy. At the same time, the morphology of the nanomaterials and their composites was analyzed by scanning electron microscopy. Specifically, the 0.8 g PBAT-CF TENG demonstrated superior performance, achieving an output voltage of 45.45 V and a current of 4.5 µA. Subsequent electrical studies, including charging commercial capacitors (1.0 to 47 μF) and powering LEDs and calculators, underscored the device’s efficiency. The PBAT-CF TENG also effectively generated voltage and current signals from physical activities like walking and jumping. This innovative approach highlights the potential for biodegradable, high-performing, self-powered flexible electronics, and wearable devices, paving the way for sustainable technological advancements.

Compatibilization of Poly(lactic acid)/Poly(propylene carbonate) blends by star-shaped multi-arm polymer with low molecular weight

Compatibilizing polymer blends via a facile and efficient manner is of great significance since polymer blends are practical in industrial applications but limit severely by poor compatibility. Herein, we propose a novel compatibilization strategy that star-shaped multi-arm polymer with low molecular weight can be an excellent compatibilizer for polymer blends. As an example of the concept, a modified tannic acid (mTA) with a star-shaped multi-arm structure is fabricated to compatibilize biodegradable poly(lactic acid)/poly(propylene carbonate) (PLA/PPC) blend. Compared to traditional compatibilization methods, mTA shows higher compatibilization efficiency and lower limitation in distribution as mTA can exert compatibilization at the interface and in PLA and PPC phases. Consequently, mTA compatibilizes the PLA/PPC blend efficiently, leading to strikingly reduced size of PPC dispersed phase and optimized interface. The mechanism is revealed to stem from the reduced interfacial tension and regulated viscosity ratio. With the improved compatibility, PLA70/PPC30/mTA4 shows an elongation at break of 307.5 ± 15.4 % and a toughness of 85.2 ± 4.5 MJ/m3, which is 680 % and 800 % of that of PLA70/PPC30 respectively. We envision that this work provides a novel and facile compatibilization strategy and will promote the fabrication of high-performance polymer blends.

Ti3C2Tx MXene-functionalized Hydroxyapatite/Halloysite nanotube filled poly– (lactic acid) coatings on magnesium: In vitro and antibacterial applications

Magnesium (Mg) stands out in temporary biomaterial applications due to its biocompatibility, biodegradability, and low Young's modulus. However, controlling its corrosion through next-generation polymer-based functional coatings is crucial due to the rapid degradation behavior of Mg. In this study, the function of 2D lamellar Ti3C2Tx (MXene) in Hydroxyapatite (HA) and Halloysite nanotube (HNT) hybrid coatings in biodegradable poly– (lactic acid) (PLA) was investigated. The morphological and structural characterizations of the coatings on Mg were revealed through HRTEM, XPS, SEM-EDX, XRD, FTIR, and contact angle analyses/tests. Electrochemical in vitro corrosion tests (OCP, PDS, and EIS-Nyquist) were conducted for evaluate corrosion resistance under simulated body fluid (SBF) conditions. The bioactivity of the coatings in SBF have been revealed in accordance with the ISO 23,317 standard. Finally, antibacterial disk diffusion tests were conducted to investigate the functional effect of MXene in coatings. It has been determined that the presence of MXene in the coating increased not only surface wettability (131°, 85°, 77°, and 74° for uncoated, pH, PHH, and PHH/MXene coatings, respectively) but also increased corrosion resistance (1857.850, 42.357, 1.593, and 0.085 × 10–6, A/cm2 for uncoated, pH, PHH, and PHH/MXene coatings, respectively). It has been proven that the in vitro bioactivity of PLA-HA coatings is further enhanced by adding HNT and MXene, along with SEM morphologies after SBF. Finally, 2D lamellar MXene-filled coating exhibits antibacterial behavior against both E. coli and S. aureus bacteria.

Interface/Dipole Polarized Antibiotics-Loaded Fe3O4/PB Nanoparticles for Non-Invasive Therapy of Osteomyelitis Under Medical Microwave Irradiation.

Due to their poor light penetration, photothermal therapy and photodynamic therapy are ineffective in treating deep tissue infections, such as osteomyelitis caused by Staphylococcus aureus (S. aureus). Here, a microwave (MW)-responsive magnetic targeting composite system consisting of ferric oxide (Fe3O4)/Prussian blue (PB) nanoparticles, gentamicin (Gent), and biodegradable poly(lactic-co-glycolic acid) (PLGA) is reported. The PLGA/Fe3O4/PB/Gent complex is used in combination with MW thermal therapy (MTT), MW dynamic therapy (MDT), and chemotherapy (CT) to treat acute osteomyelitis infected with S. aureus-infected. The powerful antibacterial effect of the PLGA/Fe3O4/PB/Gent is determined by the synergistic effects of heat and reactive oxygen species (ROS) generation by the Fe3O4/PB nanoparticles under MW irradiation and the effective release of Gent at the infection site via magnetic targeting. The antibacterial mechanism of the PLGA/Fe3O4/PB/Gent under MW irradiation is analyzed using bacterial transcriptome RNA sequencing. The MW heat and ROS reduce the activity of the protein transporters on the bacterial membrane, along with the transport of various ions and the acceleration of phosphate metabolism, which can lead to increased permeability of the bacterial membrane, damage the ribosome and DNA, and accompany the internal protein efflux of the bacteria, thus effectively killing the bacteria.

Engineering Triphasic Nanocomposite Coatings on Pretreated Mg Substrates for Biomedical Applications.

Biodegradable polymer-based nanocomposite coatings provide multiple advantages to modulate the corrosion resistance and cytocompatibility of magnesium (Mg) alloys for biomedical applications. Biodegradable poly(glycerol sebacate) (PGS) is a promising candidate used for medical implant applications. In this study, we synthesized a new PGS nanocomposite system consisting of hydroxyapatite (HA) and magnesium oxide (MgO) nanoparticles and developed a spray coating process to produce the PGS nanocomposite layer on pretreated Mg substrates, which improved the coating adhesion at the interface and their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs). Prior to the spray coating process of polymer-based nanocomposites, the Mg substrates were pretreated in alkaline solutions to enhance the interfacial adhesion strength of the polymer-based nanocomposite coatings. The addition of HA and MgO nanoparticles (nHA and nMgO) to the PGS matrix, as well as the alkaline pretreatment of the Mg substrates, significantly enhanced the interfacial adhesion strength when compared with the PGS coating on the nontreated Mg control. The average BMSC adhesion densities were higher on the PGS/nHA/nMgO coated Mg than the noncoated Mg controls under direct contact conditions. Moreover, the addition of nHA and nMgO to the PGS matrix and coating the nanocomposite onto Mg substrates increased the average BMSC adhesion density when compared with the PGS/nHA/nMgO coated titanium (Ti) and PGS coated Mg controls under direct contact. Therefore, the spray coating process of PGS/nHA/nMgO nanocomposites on Mg substrates or other biodegradable metal substrates could provide a promising surface treatment strategy for biodegradable implant applications.

Porous polylactide membranes with high piezo-catalytic efficiency for organic wastewater treatment

Piezo-catalysis has been emerged as a green and promising wastewater treatment technology for efficient removal of persistent organic pollutants (POPs), such as 4-nitrophenol (4-NP). However, it remains challenging to achieve advanced materials with combined advantages of high piezo-catalytic efficiency, good hydrophilicity, and environmental friendliness. In this work, highly crystalline porous polylactide (PLA) membranes possessing such exceptional advantages have been successfully prepared from biodegradable poly(L-lactide)/poly(D-lactide)/polyethylene glycol/polyoxyethylene-polyoxypropylene block copolymer (PLLA/PDLA/PEG/PEO-PPO-PEO) blends by melt processing and subsequent water etching. During the melt-processing, the two PLA enantiomers co-crystallize into stereocomplex (SC) crystals and simultaneously the PEG used as a porogen is expelled from the crystalline regions. The results show that the prepared PLA membranes have not only abundant micro-porous structures but also good hydrophilicity due to the preferential localization of PEO-PPO-PEO copolymer on the pore walls, thus giving rise to an extremely high water flux of 2400 L/m2h. More interestingly, the PLA membranes exhibit remarkable piezoelectric activity and the piezo-catalytic degradation efficiency of 4-NP can reach as high as 96 % under the triggering of water flow involved in vacuum filtration. In addition, the membranes show excellent reusability and the high catalytic efficiency can be well-maintained after five repeated uses. These findings suggest broad application prospects of our porous SC-PLA membranes in organic wastewater treatment.

The effect of biodegradable polymer blending on the disintegration rate of PHBV, PBS and PLA in soil

This study generates new insights into the disintegration phenomena that take place upon blending different classes of biodegradable polymers. Polymer blending is found to be an effective method to tailor the disintegration rate of these polymers in soil. It is shown that the biodegradation of poly(hydroxybutyrate-valerate) (PHBV) can be accelerated by blending with polybutylene succinate adipate (PBSA) and polycaprolactone (PCL). The observed high rate of disintegration of polybutylene succinate (PBS) in soil (severe deterioration in 4 weeks, and fragmentation in 4 months) does not fully align with its current reputation in the market as a polymer that is non-biodegradable in soil. Disintegration trials executed in soil media with different inoculants demonstrate that the biodegradation rate of PBS in soil is highly dependent on the specific soil conditions. Moreover, it is shown that the biodegradation of PBS can be substantially accelerated by blending it with PBSA (fragmentation in 8 weeks). Finally, it is shown that the disintegration of polylactic acid (PLA) in soil can be enhanced by blending it with PCL. Experiments that monitor the CO2 evolution of these blends, both in soil and in home composting environments, demonstrate that not just the disintegration, but also the overall biodegradation of PLA is enhanced by blending with PCL (39% conversion to CO2 in 12 months incubation in soil; 89% conversion to CO2 in 6 months incubation in home composting conditions). This opens up possibilities for targeted blending strategies to reduce potential accumulation of PLA-based plastics in soil environments.

Poly(malic acid) Nanoconjugates of Pyrazinoic Acid for Lung Delivery in the Treatment of Tuberculosis.

Tuberculosis (TB) remains a major global infection, and TB treatments could be improved by site-specific targeting with delivery systems that allow tissue and cell uptake. To increase the drug concentration at the target sites following lung delivery, polymeric nanoconjugates based on biodegradable poly(malic acid) were designed. Pyrazinoic acid (POA), the active moiety of pyrazinamide─a first-line antituberculosis drug─was covalently bound to poly(malic acid) using a hydrophobic linker at mole ratios of 25%, 50%, and 75%. Three linkers, hexanediol, octanediol, and decanediol, were considered. Independently of the linker or ratio, all the conjugates were able to self-assemble, forming nanoconjugates (NCs) in water with 130-190 nm in diameter. Pyrazinoic acid could be released in a controlled manner without any burst release effect. Its kinetics can be adjusted by modifying the grafting ratio and linker length. No cytotoxicity was observed on RAW 264.7 macrophages up to ∼14 μg/mL of POA. In addition, the nanoconjugates were efficiently taken up by these cells over 5 h. Thanks to their high loading capacity and modulable release profiles, these nanoconjugates hold great promise for more effective treatment of tuberculosis.

Control of encapsulation efficiency and morphology of poly(lactide-co-glycolide) microparticles with a diafiltration-driven solvent extraction process

The removal of organic solvents during the preparation of biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by an O/W- solvent extraction/evaporation process was investigated and controlled by diafiltration. Emulsification and steady replacement of the aqueous phase were performed in parallel in a single-vessel setup. During the process, the solidification of the dispersed phase (drug:PLGA:solvent droplets) into microparticles was monitored with video-microscopy and focused beam reflectance measurement (FBRM) and the residual solvent content was analyzed with headspace gas chromatography (organic solvent) and coulometric Karl-Fischer titration (water). Microparticles containing dexamethasone or risperidone were characterized with regard to particle size, morphology, encapsulation efficiency and in-vitro release. Diafiltration-accelerated solvent extraction shortened the process time by accelerating solidification of dispersed phase but reduced the residual dichloromethane content only in combination with increased temperature. Increasing the diafiltration rate increased particle size, porosity, and the encapsulation efficiency of risperidone. The latter effect was particularly evident with increasing lipophilicity of PLGA. A slower and more uniform solidification of end-capped and increased lactide content PLGA grade was identified as the reason for an increased drug leaching. Accelerated solvent extraction by diafiltration did not affect the in-vitro release of risperidone from different PLGA grades. The initial burst release of dexamethasone was increased by diafiltration when encapsulated in concentrations above the percolation threshold. Both porosity and burst release could be reduced by increasing the process temperature during diafiltration. Residual water content was established as an indicator for porosity and correlated with the burst release of dexamethasone.

Accelerated removal of solvent residuals from PLGA microparticles by alcohol vapor-assisted fluidized bed drying

The removal of residual solvents from biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by fluidized bed drying was investigated. Microparticles were prepared by the O/W solvent extraction/evaporation method and the influence of various process and formulation parameters on the secondary drying was studied. PLGA microparticles and films were characterized for residual organic solvent and water content, recrystallisation, surface morphology, drug loading and in-vitro release of the drugs dexamethasone and risperidone. While alcohol-free fluidized bed drying decreased the residual dichloromethane content only from about 7 % (w/w) to 6.4 % (w/w) (18 °C) or 3.2 % (w/w) (35 °C) within 24 h, 140 mg/L methanol vapor in purge gas facilitated almost complete removal of dichloromethane or ethyl acetate from microparticles (0–0.11 % (w/w) after 6 h). By controlling the alcohol concentration and temperature of the purge gas, the alcohol absorption and complete removal was controlled. Risperidone increased the methanol absorption enhancing the plasticization. A high initial residual water content was identified to promote aggregation and was eliminated by starting fluidized bed drying without alcohol. Alcohol vapor-assisted fluidized bed drying accelerated microparticle manufacturing without affecting the redispersibility, the drug loading and the in-vitro release of risperidone and dexamethasone.

Hierarchically Nano-Decorated Poly(lactic acid) Nanofibers for Humidity-Resistant Respiratory Healthcare and High-Accuracy Disease Diagnosis.

The application of biodegradable and eco-friendly poly(lactic acid) (PLA) nanofibrous membranes (NFMs) toward respiratory healthcare has long been thwarted by the poor electroactivity and low surface activity of PLA. Herein, we unravel a microwave-assisted route to fabricate rod-like ZnO nanodielectrics, which were decorated with dopamine (ZnO@PDA) and anchored at the PLA nanofibers via an electrospinning-electrospray approach. The PLA/ZnO@PDA NFMs featured a substantially elevated specific surface area (up to 20.7 m2/g), increased dielectric constant (nearly 1.8) and a surface potential as high as 9.5 kV, resulting in superior air filtering performance (99.45% for PM0.3, 94.1 Pa, 32 L/min) compared with the pure PLA counterpart (90.04%, 169.0 Pa, 32 L/min). The notably increased electroactivity endowed the PLA/ZnO@PDA NFMs with significant improvements in triboelectric properties (output voltage of 11.5 V at 10 N, 0.5 Hz), laying down the cornerstone for self-powered monitoring of personal respiration. More importantly, a deep learning-assisted diagnostic system was developed based on respiration-driven signal patterns, enabling intelligent and real-time disease diagnosis with 100% accuracy for the protective membranes. The proposed hierarchical nanodecoration strategy opens up new possibilities for engendering eco-friendly nanofibers with an exceptional combination of efficient respiratory healthcare and intelligent diagnosis.

Partially Bio-Based and Biodegradable Poly(Propylene Terephthalate-Co-Adipate) Copolymers: Synthesis, Thermal Properties, and Enzymatic Degradation Behavior.

A series of partially bio-based and biodegradable poly(propylene terephthalate-co-adipate) (PPTA) random copolymers with different components were prepared by the melt polycondensation of petro-based adipic acid and terephthalic acid with bio-based 1,3-propanediol. The microstructure, crystallization behavior, thermal properties, and enzymatic degradation properties were further investigated. The thermal decomposition kinetics was deeply analyzed using Friedman's method, with the thermal degradation activation energy ranging from 297.8 to 302.1 kJ/mol. The crystallinity and wettability of the copolymers decreased with the increase in the content of the third unit, but they were lower than those of the homopolymer. The thermal degradation activation energy E, carbon residue, and reaction level n all showed a decreasing trend. Meanwhile, the initial thermal decomposition temperature (Td) was higher than 350 °C, which can meet the requirements for processing and use. The PPTA copolymer material still showed excellent thermal stability. Adding PA units could regulate the crystallinity, wettability, and degradation rate of PPTA copolymers. The composition of PPTA copolymers in different degradation cycles was characterized by 1H NMR analysis. Further, the copolymers' surface morphology during the process of enzymatic degradation also was observed by scanning electron microscopy (SEM). The copolymers' enzymatic degradation accorded with the surface degradation mechanism. The copolymers showed significant degradation behavior within 30 days, and the rate increased with increasing PA content when the PA content exceeded 45.36%.

Fluorescent, pH, and UCST Responsive Polymer Nanomaterials for Treatment of Recurrent Miscarriage.

Recurrent miscarriage (RM), defined as three or more consecutive spontaneous miscarriages, affects many women of childbearing age. The pathological basis of RM is an imbalance in apoptosis, with the MDM2-p53 pathway playing a crucial role. In this study, we synthesized poly(6-acetoxyl-ε-caprolactone)-graft-(4-amino-benzimidazole) (PCCL-4-ABI) by modifying poly(6-acetoxyl-ε-caprolactone) (PCCL) with 4-amino-benzimidazole (4-ABI). The introduction of carboxyl and 4-ABI groups endowed the PCL backbone with fluorescence, pH responsiveness, and UCST responsiveness. The temperature-dependent release behavior of compound 1-loaded PCCL-4-ABI nanofluorescent materials was attributed to UCST transition. We successfully developed a novel nanofluorescent polymer drug delivery platform, PCCL-4-ABI@1, and evaluated its regulatory effects on p53 and MDM2 in trophoblast cells (HTR-8/SVneo). The results showed that the system loaded with low molecular weight heparin increased MDM2 and decreased p53 expression in a dose-dependent manner, thereby inhibiting trophoblast cell apoptosis. This study developed a biodegradable poly(ε-caprolactone) with UCST behavior, significant for the advancement of thermoresponsive fluorescent nanoparticle systems.