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In this paper, polyurethane nanofibers (PU)/chitosan (CS)/zinc oxide nanoparticles (ZnO)/ Glutathione (GSH) were prepared as wound dressings using the electrospinning method. First, the antibacterial effect of ZnO nanoparticles against Escherichia coli and Staphylococcus aureus was investigated. Second, the ability of the nanofibers to release different amounts of antibiotics and nanoparticles to prevent wound infection was investigated. The morphology of the composite nanofibers was investigated using field emission electron microscopy (FESEM). The chemical structure of the nano-wound dressing was examined using infrared spectroscopy (FTIR), and the FTIR spectroscopy results showed that GSH and ZnO nanoparticles were successfully arranged within the nanofibers. with an increase in the amount of GSH (1,3,5 wt%) at a constant voltage of 0.4 V, the amount of current increased by 1.7, 2.1, and 6.2 μA, respectively. According to the results of electrochemical analysis, the optimal amount of active ingredient is 5 wt%, but according to the images of FESEM analysis, due to the lack of nanofibers with the corresponding morphology, the amount of active ingredient is reduced to 5 wt% PU/Chi/. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) combined with pemetrexed (MTA) is commonly employed in the treatment of advanced non‐small cell lung cancer. However, conventional clinical administration methods fail to achieve precise spatiotemporal delivery within the tumor microenvironment (TME), resulting in inadequate control of local drug concentrations and impeding the synergistic efficacy of chemotherapeutic drugs. Aiming to address this issue, Fe2O3 hollow multi‐shelled structure (HoMS) nanocarriers with spatiotemporally controlled release properties and co‐encapsulated CDDP and MTA into this nanocarrier are developed. The confined microenvironment provided by Fe2O3‐HoMS enables a targeted and temporal sequential drug release tailored to clinical requirements. Furthermore, chemotherapy‐induced DNA damage leads to apoptosis, accompanied by a substantial generation of reactive oxygen species (ROS). The disruption of ROS homeostasis subsequently activates the ferroptosis pathway mediated by Fe2O3‐HoMS. In summary, Fe2O3‐HoMS exhibits a highly controlled and temporal sequential release of two chemotherapeutic drugs in TME, and the HoMS nanocarriers are further involved in the regulation of ferroptosis, realizing a triple sequential delivery system comprising CDDP‐MTA‐Fe2+ and thus significantly enhancing the anti‐tumor efficacy against lung cancer. This study proposes a novel approach for temporal sequential drug delivery by optimizing nanocarrier design, addressing the clinical challenge of precisely controlled drug release within tumors. [ABSTRACT FROM AUTHOR]

Large bone defect repair is a striking challenge in orthopedics. Currently, inorganic-organic composite scaffolds are considered as a promising approach to these bone regeneration. Silicon ions (Si4+) are bioactive and beneficial to bone regeneration and Si4+-containing inorganic mesoporous silica (MS) can effectively load drugs for bone repair. To better control the release of drug, we prepared biodegradable MS/PLGA (MP) microspheres. MP loaded organic silk fibroin/carboxymethyl chitosan/sodium alginate (MP/SF/CMCS/SA) composite scaffolds were further constructed by genipin and Ca2+ crosslinking. All MP/SF/CMCS/SA scaffolds had good swelling ability, degradation rate and high porosity. The incorporation of 1% MP significantly enhanced the compressive strength of composite scaffolds. Besides, MP loaded scaffold showed a sustained release of Si4+ and Ca2+. Moreover, the release rate of rhodamine (a model drug) of MP/SF/CMCS/SA scaffolds was obviously lower than that of MP. When culturing with rat bone marrow mesenchymal stem cells, scaffolds with 1% MP displayed good proliferation, adhesion and enhanced osteogenic differentiation ability. Based on the results above, the addition of 1% MP in SF/CMCS/SA scaffolds is a prospective way for drug release in bone regeneration and is promising for further in vivo bone repair applications. [ABSTRACT FROM AUTHOR]

This study aimed to prepare a polyvinyl alcohol/sodium alginate (PVSA) nanofibrous mat as an amoxicillin (AMOX) delivery system. AMOX was loaded to the PVSA nanofibers during electrospinning, and the AMOX-loaded PVSA (PVSA/AMOX) nanofibrous mat was cross-linked by glutaraldehyde (GA). The PVSA/AMOX nanofibrous mat was characterized by Fourier Transform infrared spectroscopy, scanning electron microscopy, Brunauer–Emmett–Teller, and mercury porosimetry analyses. The thickness, air permeability, and water vapor transmission rate of the PVSA/AMOX nanofibrous mat were 0.43 ± 0.08 mm, 17.2 ± 4.91 L/m2/s, and 1485 ± 13.6 g/m2/d, respectively, which were suitable for wound dressing applications. The tensile strength was 6.73 ± 0.48 MPa and elongation at a maximum load was 81.9 ± 17.0%, within the ranges of human skin's values. The total porosity was 59.4%, enabling cell adhesion, migration, and proliferation. The PVSA/AMOX nanofibrous mat has high swelling (319 ± 4.2%) and low degradation (2.2 ± 0.1% in 10 days) ratios. The nanofibrous mat cross-linked with 0.25% GA solution for 20 min had a 73.07% cumulative release for 90 min. The drug release kinetics were obeyed to the Korsmeyer-Peppas model. The nanofibrous mat presented antibacterial activity on S. aureus ATCC 29213 and E. coli ATCC 25922, and there was no cytotoxic effect on the human normal keratinocyte cells, demonstrating the potential for use in wound dressing applications. [ABSTRACT FROM AUTHOR]

Selenium (Se) compounds hold promise as potential therapeutics for cancer due to their diverse biological functions and redox‐regulating properties. In this study, the encapsulation of a hydrophobic selenium compound inside 5 µm sized biodegradable polyelectrolyte capsules consisting of poly‐L‐arginine and dextran is investigated. While the encapsulated form of the compound showed comparable cellular uptake and cytotoxicity as the free drug, e.g. no improved anti‐cancer efficacy is achieved, the investigation yielded crucial insights. Utilizing subcellular resolution synchrotron X‐ray fluorescence imaging (XFI), the intracellular location of the Se compound is successfully visualized by demonstrating the degradation of the capsules and the following redistribution of the compound, without exogenous labeling. By applying a quantitative fitting approach, the intracellular Se mass is determined to be 0.09 ± 0.01 pg after degradation of the carrier. This highlights the potential of XFI as a powerful tool for tracking intracellular dynamics of metal‐based drugs, which may facilitate drug development in the clinic. [ABSTRACT FROM AUTHOR]

In the biomedical industry, microneedles have gained significant attention as a painless method for dermal and transdermal drug delivery. Depending on their intended use, microneedles can be fabricated in various sizes, shapes, and materials. To enhance skin permeability, versatile microneedles have been developed using a range of microfabrication technologies. This review focuses on the fabrication methods of microneedles made from polymeric materials, which are favored for microscale fabrication due to their ease of processing. Additionally, we discuss methods to improve the robustness of polymeric microneedles by coating them with metallic films or inorganic nanoparticles. [ABSTRACT FROM AUTHOR]

Chitosan and collagen are two valuable biopolymers for the synthesis and design of biomaterials. In this work, we evaluate the effect of the concentration of chitosan on the physicochemical and biological properties of polyurethane‐crosslinked collagen hydrogels. Chitosan was added with a proportion ranging from 0 to 40 wt%. Depending on the aminoglycoside content, semi‐interpenetrating polymeric networks (semi‐IPNs) or completely IPNs were generated; this is attributed to the occlusion of the chitosan granules in the reticulated fibrillar matrix. The presence of chitosan in these hydrogels provides antibacterial capacity against pathogenic microorganisms such as Escherichia coli, which is corroborated by inhibition halo experiments. Hydrogels with 40 wt% of chitosan only showed improvement in the gelation time and mechanical performance, indicating a dependent relation of these properties with respect to the aminopolysaccharide content. Hydrogels with 10 wt% of chitosan showed the best biomedical performance. They also have the highest reticulation, swelling capability and chemical stability against degradation events such as hydrolysis and proteolysis. Further, they have the best biocompatibility for human monocytes, and they stimulate the secretion of monocyte chemotactic protein‐1 and tumor necrosis factor‐alpha. Also, these hydrogels showed a controlled release of ketorolac at pH 7 and 37 °C. The results of these in vitro biological tests demonstrate the potential application of novel biopolymer‐based hydrogels in chronic wound healing due to their antibacterial capacity and modulation of the biological response of specialized cells in dermal repair treatments, as well as for the design of smart materials for the controlled release of drugs. © 2023 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

Bedaquiline is a drug used for the treatment of multidrug-resistant TB in adults and children that is currently only commercially available in tablet form. The present study was aimed at preparing nanoemulsion (NE) of BDQ using natural vegetable oils to deliver BDQ. The optimisation of surfactant mixtures was undertaken using Design of Experiments (DoE), specifically an optimal mixture design. The NEs were optimised while monitoring droplet size (DS), zeta potential (ZP), polydispersity index (PDI) and drug content (DC). The optimised NEs were further characterised using transmission electron microscopy, electrical conductivity, viscosity, pH and in vitro release studies. The optimised NE showed values of 191.6 nm ± 2.38 nm, 0.1176 ± 1.69, -25.9 mV ± 3.00 mV and 3.14 ± 0.82 mg/ml for DS, PDI, ZP and DC respectively. Furthermore, the TEM studies demonstrated the spherical shape of the optimised globules. The nanoemulsion was characterised by measuring its electrical conductivity, viscosity and pH which were determined as 53.1 µS/cm, 327 ± 3.05 cP and 5.63 ± 1.78, respectively. In conclusion, these NEs have great potential for improving solubility, drug delivery, and administration of BDQ. However, further studies are required to maximise the drug content and to demonstrate to what extent these NE have effect against MDR-TB. [ABSTRACT FROM AUTHOR]

Background: Electrospun nanofiber scaffolds have been widely used in tissue engineering because they can mimic extracellular matrix-like structures and offer advantages including high porosity, large specific surface area, and customizable structure. In this study, we prepared scaffolds composed of aligned and random electrospun polycaprolactone (PCL) nanofibers capable of delivering basic fibroblast growth factor (bFGF) in a sustained manner for repairing damaged tendons. Results: Aligned and random PCL fiber scaffolds containing bFGF-loaded bovine serum albumin (BSA) nanoparticles (BSA-bFGF NPs, diameter 146 ± 32 nm) were fabricated, respectively. To validate the viability of bFGF-loaded aligned PCL nanofiber scaffold (aPCL + bFGF group) in tendon tissue engineering, we assessed the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage and the in vivo regeneration of tendons using a rat Achilles tendon defect model. The encapsulated bFGF could be delivered in a sustained manner in vitro. The aPCL + bFGF scaffold promoted the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage. In the repair of a rat Achilles tendon defect model, the aPCL + bFGF group showed a better repair effect. The scaffold offers a promising substrate for the regeneration of tendon tissue. Conclusions: The aligned and random PCL fiber scaffolds containing bFGF nanoparticles were successfully prepared, and their physical and chemical properties were characterized. The aPCL + bFGF scaffold could promote the expression of the related genes and proteins of tendon-forming, facilitating tendon differentiation. In the rat Achilles tendon defect experiments, the aPCL + bFGF exhibited excellent tendon regeneration effects. [ABSTRACT FROM AUTHOR]

Glycerol-(9,10-trioxolane) trioleate (OTOA) is a promising material that combines good plasticizing properties for PLA with profound antimicrobial activity, which makes it suitable for application in state-of-the-art biomedical and packaging materials with added functionality. On the other hand, application of OTOA in PLA-based antibacterial materials is hindered by a lack of knowledge on kinetics of the OTOA release. In this work, the release of glycero-(9,10-trioxolane) trioleate (OTOA) from PLA films with 50% OTOA content was studied during incubation in normal saline solution, and for the first time, the kinetics of OTOA release from PLA film was evaluated. Morphological, thermal, structural and mechanical properties of the PLA + 50% OTOA films were studied during incubation in normal saline and corresponding OTOA release using differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy and mechanical tests. It was confirmed by DSC and XRD that incubation in the saline solution and corresponding OTOA release from PLA film does not lead to significant changes in the structure of the polymer matrix. Thus, the formation of more disturbed α' crystalline phase of PLA due to partial hydrolysis of amorphous zones and/or most unstable crystallites in the PLA/OTOA semi-crystalline structure was observed. The degree of crystallinity of PLA + OTOA film was also slightly increased at the prolonged stages of OTOA release. PLA + 50% OTOA film retained its strength properties after incubation in normal saline, with a slight increase in the elastic modulus and tensile strength, accompanied by a significant decrease in relative elongation at break. The obtained results showed that PLA + 50% OTOA film could be characterized by sustained OTOA release with the amount of released OTOA exceeding 50% of the initial content in the PLA film. The OTOA release profile was close to zero-order kinetics, which is beneficial in order to provide stable drug release pattern. Developed PLA + 50% OTOA films showed a strong and stable antibacterial effect against Raoultella terrigena and Escherichia coli, bacterial strains with multidrug resistance behavior. The resulting PLA + OTOA films could be used in a variety of biomedical and packaging applications, including wound dressings and antibacterial food packaging. [ABSTRACT FROM AUTHOR]

Intramolecular bonds in small organic molecules, macromolecules, and organic-inorganic hybrids are broken or formed by ultrasound-activated mechanical force that can be applied with spatial and temporal precision for contactless external control of mechanochemical reactions. Ultrasound featuring non-invasiveness, high tissue penetration, and spatiotemporal controllability has shown great potential in controlling the activation of mechanochemical reactions such as chemical bond scission, natural enzyme activation, and catalytic radical generation for targeted drug or gene therapy. Here, we comprehensively summarize the latest research and future trends in ultrasound-activated mechanochemical reactions for smart biomedical applications. First, the mechanism of ultrasound-activated mechanochemical reactions will be outlined. Then, the types of mechanochemical reactions will be carefully discussed. After that, the representative biomedical applications have been summarized from a unique perspective. Finally, we systematically emphasize the current challenges and future outlooks to guide the rational design of ultrasound-activated drug release over conventional drug-loaded therapies. We believe that this review will substantially facilitate the progression and widespread utilization of ultrasound-activated mechanochemical reactions in biomedical applications. [ABSTRACT FROM AUTHOR]

Background: Achieving a balance between stable drug loading/delivery and on-demand drug activation/release at the target sites remains a significant challenge for nanomedicines. Carrier-free prodrug nanoassemblies, which rely on the design of prodrug molecules, offer a promising strategy to optimize both drug delivery efficiency and controlled drug release profiles. Methods: A library of doxorubicin (DOX) prodrugs was created by linking DOX to fatty alcohols of varying chain lengths via a tumor-responsive disulfide bond. In vitro studies assessed the stability and drug release kinetics of the nanoassemblies. In vivo studies evaluated their drug delivery efficiency, tumor accumulation, and antitumor activity in mouse models. Results: In vitro results demonstrated that longer fatty alcohol chains improved the stability of the nanoassemblies but slowed down the disassembly and drug release process. DSSC16 NAs (hexadecanol-modified DOX prodrug) significantly prolonged blood circulation time and enhanced tumor accumulation, with AUC values 14.2-fold higher than DiR Sol. In 4T1 tumor-bearing mouse models, DSSC16 NAs exhibited notably stronger antitumor activity, resulting in a final mean tumor volume of 144.39 ± 36.77 mm3, significantly smaller than that of all other groups (p < 0.05 by ANOVA at a 95% confidence interval). Conclusions: These findings underscore the critical role of prodrug molecule design in the development of effective prodrug nanoassemblies. The balance between stability and drug release is pivotal for optimizing drug delivery and maximizing therapeutic efficacy. [ABSTRACT FROM AUTHOR]