Journal of Biomaterials Science, Polymer Edition最新文献

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic options, largely due to challenges in delivering drugs across the blood-brain barrier (BBB). In this study, we synthesized folic acid (FA) conjugated amphiphilic copolymers via reversible addition-fragmentation chain transfer (RAFT) polymerization to enhance the targeted delivery of donepezil (DZP) to the brain. The copolymers were self-assembled into micelles and extensively characterized for their size, zeta potential, and stability using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The micelles were further evaluated for their ability to cross an in vitro BBB model and their cellular uptake by brain endothelial cells. FA conjugation was employed to exploit the folate receptor-mediated transport mechanism, which has shown potential for improving drug delivery across the BBB. This study demonstrates the feasibility of using FA functionalized micelles as a targeted delivery system, offering potential advancements in the treatment of Alzheimer's disease.

Nanotechnology is expanding rapidly, leading to the continual development of new applications. Therefore, it is crucial to understand the effects of nanoparticles (NPs) and their components to develop more efficient formulations with greater potential applications. Here, we evaluated the influence of polymer and surfactant composition on NP toxicity. Our results revealed significant variations in toxicity based on NP composition. The type of polymer used to prepare the NPs affects their properties, especially in terms of cell tolerance. Notably, cell viability ranged from 6% to 100% depending on the NPs' composition. In general, NPs based on Eudragit^® RL 100 exhibited greater cytotoxicity and hemolysis rates than those based on PCL, PLGA, and chitosan. This highlights the critical role of polymer selection in determining toxicity. Additionally, including Span 80^® in the NP matrix amplified its toxic effects, which emphasizes the importance of surfactant choice in NP design. Both nanospheres and nanocapsules based on the same polymer displayed comparable toxicological profiles. Although smaller NPs exhibited higher toxicity, a direct correlation between size and toxicity could not be established, since the increased toxicity of smaller NPs was primarily attributed to the presence of Span 80^® in the composition. Finally, all formulations, except the nanospheres based on Eudragit^® RL 100, maintained colloidal stability in a protein-rich environment, indicating that no secondary structures were formed. Therefore, our data suggest that NP constituents can critically contribute to its toxicity, highlighting the importance of toxicological and safety studies to better understand the effects of nanoformulations.

Synthesis and characterization of a new bio-inspired low molecular weight inorganic-organic hybrid polymer with tunable properties and multifunctionality for in situ polymerization and cross linking. The hybrid bioactive polymer was synthesized through modified sol-gel method using 3- trimethoxy silyl propyl methacrylate as the precursor. The new polymer was characterized using Proton Nuclear Magnetic Resonance (¹H-NMR), Carbon-13 Nuclear Magnetic Resonance Spectroscopy (¹³C- NMR), Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM) for confirming the existence of inorganic as well as organic entities in the material. The volumetric shrinkage and bioactivity of the newly synthesized polymer was analyzed using Micro Computed Tomography (µ-CT) and Scanning Electron Microscopy (SEM). The excellent bioactivity with low polymerization shrinkage compared to the conventional resin used in biomedical applications, makes the new bio-inspired inorganic-organic hybrid bioactive polymer a potential resin matrix for the development of dental composites, bone cements and for coating applications.

The exceptional ability of molecularly imprinted polymers (MIPs) to recognize specific molecular structures has recently facilitated their use in biomedical applications, including drug release. Controlled nasal drug release techniques effectively target specific tissues with optimal doses, timing, and location for therapeutic effects. This approach is advantageous due to the slightly acidic pH and low enzymatic activity in this region. MIPs are employed in these areas to enhance specificity and efficacy in drug release systems. This study aims to design an effective controlled nasal drug release system by imprinting the antiretroviral drug Ritonavir (RTV) onto pHEMA-based molecularly imprinted nanoparticles. Attenuated total reflection Fourier-transform infrared spectroscopy (FTIR-ATR), zeta-size analysis, and scanning electron microscopy (SEM) were used to characterize the nanoparticles, verifying their spherical shape, content and consistent size distribution. Zeta-size analysis revealed that RTV-imprinted p(HEMA-MATrp) nanoparticles had an average size of 88.46 nm with a polydispersity index of 0.279. The MIP nanoparticles possessed a specific surface area of 628.34 m²/g. In vitro release studies showed controlled release behavior of RTV-loaded nanoparticles, fitting the Korsmeyer-Peppas model. At 2.0 mg/mL, 71% cumulative release was observed after 10 h. The cumulative release of the was lowest at pH 4.0 (26%) and highest at pH 7.4 (32%) for 1.0 mg/mL loaded p(HEMA-MATrp) nanoparticles. MTT cytotoxicity tests on L929 cells indicated reduced cytotoxicity and good biocompatibility. These results suggest RTV-imprinted p(HEMA-MATrp) nanoparticles as an effective drug release system for antiretroviral therapies.

Restoring cartilage to healthy state is challenging due to low cell density and hence low regenerative capacity. The current platforms are not compatible with clinical translation and require dedicated handling of trained personnel. However, by engineering and implanting cell microaggregates in higher concentrations, efficient formation of new cartilage can be achieved, even in the absence of exogenous growth factors. Therefore, one-step surgeries are preferable for novel treatments and we need cell laden microgels allowing the formation of microaggregaets in vivo. Injectability is a key parameter for in situ forming the shape and minimally invasive clinical applications. Hydrogels as bioinks can restore damaged tissues to their primary shape. Chitosan is a polysaccharide derived from chitin with abundant usage in tissue engineering. This review highlights the use of chitosan as an injectable hydrogel for osteochondral defects. Several studies focused on encapsulating mesenchymal stem cells within chitosan hydrogels have been categorized and incorporating microfluidic devices has been identified in the forefront to form microgels. Additionally, the printability is another convenience of chitosan for using in 3D printing for cartilage tissue engineering which is described in this review.

Hyaluronic acid, a non-sulphated glycosaminoglycan has attracted its usage in the management of breast cancer. Drug-loaded nanoparticles with hyaluronic acid surface modifications show potential as a promising method for targeting and delivering drugs to the tumor site. The aim of this study was to conduct a systematic review of articles and assess the impact of hyaluronic acid coated nanoparticles on breast cancer. The various database were used for this comprehensive review. The inclusion and exclusion criteria were selected according to the PRISMA guidelines. Studies associated with characterization, in vitro, and in vivo studies were collected and subjected for further analysis. According to the inclusion criteria, 41 literature were selected for analysis. From all the studies, it was observed that the nanoparticles coated with hyaluronic acid produced better particle size, shape, zeta potential, increased in vitro cytotoxicity, cellular uptake, cell apoptosis, and anti-tumor effect in vivo. Research has shown that hyaluronic acid exhibits a higher affinity for CD44 receptors, resulting in enhanced targeted nanoparticle activity on cancer cells while sparing normal cells.

Considering cellular uptake promotion of lecithin and high expression of phospholipase in S. aureus, we designed curcumin (Cur)-loaded soy lecithin-based mPEG-PVL copolymer micelles (MPPC). The effect of soy lecithin on the anti-S. aureus activity of the formulation was studied with cur-loaded mPEG-PVL micelles (MPC without soy lecithin) as control. It was found that MPPC enhanced the water-solubility of Cur, and showed slow and sustained release behavior of Cur. Although MPPC had the same anti-S. aureus activity as Cur, its activity was significantly higher than MPC due to the cellular uptake promotion of soybean lecithin. It was noted that MPPC had good inhibition or destruction effect on biofilm, significant cell membrane damage, strong inhibition effect on protease or lipase production, and obvious induction effect on ROS expression when compared with Cur and MPC. So, the introduction of soy lecithin could improve the antibacterial activity of Cur. The lecithin-based micelles would offer potential to deliver antibacterial drugs for improved therapeutic action.

Damage to articular cartilage is irreversible and its ability to heal is minimal. The development of articular cartilage in tissue engineering requires suitable biomaterials as scaffolds that provide a 3D natural microenvironment for the development and growth of articular cartilage. This study aims to investigate the applicability of a 3D printed CSH (collagen type II/silk fibroin/hyaluronic acid) scaffold for constructing cartilage tissue engineering. The results showed that the composite scaffold had a three-dimensional porous network structure with uniform pore sizes and good connectivity. The hydrophilicity of the composite scaffold was 1071.7 ± 131.6%, the porosity was 85.12 ± 1.6%, and the compressive elastic modulus was 36.54 ± 2.28 kPa. The creep and stress relaxation constitutive models were also established, which could well describe the visco-elastic mechanical behavior of the scaffold. The biocompatibility experiments showed that the CSH scaffold was very suitable for the adhesion and proliferation of chondrocytes. Under dynamic compressive loading conditions, it was able to promote cell adhesion and proliferation on the scaffold surface. The 3D printed CSH scaffold is expected to be ideal for promoting articular cartilage regeneration.

Celastrol (CEL) belongs to the group of non-steroidal immunosuppressants with the potential to improve cardiac hypertrophy (CH). However, the poor biocompatibility and low bioavailability of CEL limit its in vivo application. This study was aimed to develop a targeted drug delivery system that can efficiently and safely deliver CEL to target tissues, providing a research basis for the application of CEL in CH therapy. A novel ROS-sensitive drug-loaded nanomicelle, dodecanoic acid (DA)-phenylboronic acid pinacol ester-dextran polymer encapsulating CEL (DBD@CEL), was synthesized using chemical synthesis. Then, the morphology, particle size, drug-loaded content, and ROS-responsive release behavior of DBD@CEL were studied. Pharmacokinetics and biocompatibility were evaluated using healthy mice. Finally, the ability and mechanism of DBD@CEL in improving CH in vivo were investigated using a mouse CH model. DBD@CEL was successfully prepared with a drug loading of 18.9%. It exhibited excellent stability with an average particle size of 110.0 ± 1.7 nm. Within 48 h, DBD@CEL released only 19.4% in the absence of H₂O₂, while in the presence of 1 mM H₂O₂, the release rate increased to 71.5%. Biocompatibility studies indicated that DBD@CEL did not cause blood cell hemolysis, had no impact on normal organs, and did not result in abnormal blood biochemical indicators, demonstrating excellent biocompatibility. In vivo studies revealed that DBD@CEL regulated the activation of NF-κB signaling, inhibits pyroptosis and oxidative stress, and thereby ameliorates CH. The ROS-responsive DBD@CEL nanodrug delivery system enhances the therapeutic activity of CEL for CH, providing a promising drug delivery system for the clinical treatment of CH.

Due to the complexity of oral physiology and pathology, the treatment of oral diseases faces multiple and complex clinical requirements. Mucosa-adhesive films (MAFs) with a single layer have demonstrated considerable potential in delivering therapeutic bioactive ingredients directly to the site of oral diseases. However, their functions are often hindered by certain factors such as limited loading capacity, poor site specificity, and sensitivity to mechanical stimuli. To overcome these limitations, the development of multi-layer MAFs has become a focal point for recent research. This involves the improvement of construction methods for multi-layer MAFs to minimize potential health risks from residual solvents, and conducting comprehensive in vivo studies to evaluate their safety and therapeutic efficacy more accurately, thus paving the way for their commercialization. Additionally, the exploration of multi-layer MAFs as personalized drug delivery systems could further broaden their application prospect. Precisely, multi-layer MAFs compensate for the shortcomings of current therapeutic strategies for oral diseases to a great extent, indicating a promising future in the market.