Macromolecular bioscience最新文献

Glaucoma, a major global health issue, is the second leading cause of blindness. Topical eye drops are commonly used due to their simplicity, but the eye's protective barriers hinder optimal drug concentration at the target site. This study addresses these challenges by developing a novel dual-drug delivery system, integrating polycaprolactone microparticles loaded with latanoprost(hydrophobic) and timolol maleate(hydrophilic) antiglaucoma drugs into a gelatin-alginate hydrogel matrix. There is a fundamental challenge to combine both drugs in the same delivery system with a controlled release profile. Hydrogel-microparticles(HMPs) were assessed via in vitro drug-release and cell culture for biocompatibility with Raman analysis for chemical compatibility and drug diffusivity. Results showed that the hydrogel-microparticle system has prolonged drug release for up to 32 days. Raman analysis confirmed the chemical compatibility of the formulation components, and in vitro biocompatibility studies demonstrate that the HMPs system is biocompatible and exhibits minimal toxicity to the cells. This novel HMPs system can serve as a flexible, controlled release platform modulating the release profile. Our study highlights that the polymer and drug properties, along with the external matrix, were key factors influencing the drug release behavior of the formulations, and the proposed HMPs system can potentially be considered for glaucoma therapy.

Pre-vascularization through endothelial cell seeding within 3D-bioprinted constructs holds great promise to advance tissue engineering vascularization strategies. Herein, the effect of biophysical (bulk modulus (0.50–76.09 kPa), local elasticity (3.65–53.68 kPa), roughness (421.07–858.30 nm)) and biochemical (0, 25 ng/mL VEGF-A or 3 mg/mL adenosine) cues in widely used bioinks (methacryloyl vs. thiol-norbornene modified gelatins incorporating 6.21–25.81 mM crosslinked moieties) was systematically investigated on the adhesion, morphology, proliferation and angiogenic signaling of seeded human umbilical vein endothelial cells. Chain-growth networks exhibited an enhanced roughness together with the need for a higher concentration of converted moieties to obtain a non-statistically significant local substrate elasticity compared to the step-growth substrates (5 w/v% GelNBSH DS 74/67 vs. 5 w/v% GelMA DS 67: 6.02 ± 2.94 vs. 3.85 ± 1.24 kPa with 6.21 vs. 7.33 mM crosslinked moieties). Despite bulk compressive moduli with insignificant difference (5 w/v% GelNBSH DS 74/67 vs. 5 w/v% GelMA DS 99: 13.57 ± 0.56 vs. 14.18 ± 1.59 kPa), the 5 w/v% GelNBSH DS 74/67 networks outperformed the 5 w/v% GelMA DS 99 samples, especially through enhanced early and more mature angiogenic signaling (Ang-2, HB-EGF, VEGF-C, FGF-1, IL-8, Endothelin-1) after 1 day of culture, while chain-growth networks required VEGF-A supplementation to attain similar signaling.

Ultrasound-responsive drug delivery systems have emerged as a promising approach in cancer therapy, offering enhanced targeting precision, controlled drug release, and reduced systemic toxicity. These systems utilize the mechanical and thermal effects of ultrasound to enable the spatiotemporally triggered release of therapeutic payloads in tumor sites. This review provides an overview of the key mechanisms underlying ultrasound-responsive drug delivery, including the activation of sonosensitizers and prodrugs, as well as the role of ultrasound-responsive nanocarriers such as liposomes, micelles, nanobubbles, and metal–organic frameworks. We explore the biophysical effects of ultrasound, including mechanical cavitation and thermal effects, that enable localized drug release and their application in enhancing the permeability of tumor tissues. Additionally, the combination of ultrasound with other therapeutic modalities such as chemotherapy, immunotherapy, and gene therapy is discussed, highlighting the synergistic potential of multimodal treatment strategies. Despite the promising preclinical findings, challenges remain, such as optimizing ultrasound parameters, improving nanocarrier stability, and ensuring clinical translation. Future research is directed toward overcoming these limitations and expanding the clinical applicability of ultrasound-responsive drug delivery systems in cancer treatment. Integrating ultrasound-triggered systems with advanced imaging technologies offers a pathway toward precision medicine, allowing for tailored cancer therapies with minimized off-target effects.

Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to its molecular heterogeneity and resistance to conventional therapies. This study presents a high-integrity nanoemulsion (NE) formulation designed to enhance the delivery and stability of the Toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) for immunotherapy. Neutral and negatively charged NEs were developed with and without the reactive lipophilic compound ricinoleic acid. Physicochemical characterization and in vitro studies in RAW 264.7 macrophages and 4T1 TNBC cells demonstrated that R848-loaded NEs exhibit prolonged shelf-life, minimal protein binding, and efficient cellular uptake. Incorporation of ricinoleic acid improved drug retention and delivery, likely through enhanced drug-lipid interactions. Molecular profiling in 4T1 cells revealed modulation of key biomarkers (TLR4/7, Cyclin D1, NF-κB), induction of autophagy (LC3II, p62, Beclin-1), and upregulation of PD-L1 expression. These dual effects, autophagy-mediated antitumor mechanisms and immune checkpoint modulation, highlight the potential of R848-NEs as a synergistic partner in anti-PD-L1 combination therapy, offering a promising strategy for TNBC treatment.

Using Response Surface Methodology (RSM) to optimise cultivation conditions showed that Trichoderma koningiopsis EPS biosynthesis depended on an alkaline pH (>9.0) and a high nitrogen concentration (≥20 g/L). This resulted in a yield increase of over 60% compared to the control conditions. Three wall polymer fractions were extracted from the obtained biomass: cold water soluble (WPSZ), hot water soluble (WPSC), and alkali soluble (WPSNaOH). These accounted for 13.3, 1.8, and 20.2% of the dry weight of the mycelium, respectively. Structural analyses revealed that the obtained EPS was mannan, with the WPS fractions consisting predominantly of (1→4)-Glc residues branching at the (1→3,6) and (1→4,6) positions. FT-IR and FT-Raman analyses revealed that α-bonds predominated in the WPSZ and WPSC fractions, whereas β-bonds predominated in the EPS and WPSNaOH fractions. This was confirmed by NMR analysis. The obtained polymer fractions (PS) exhibited antioxidant properties using the ABTS, DPPH, and FRAP methods, as well as the ability to bind bisphenol A from an aqueous environment. The most significant property of PS polymers is their ability to reduce germination and inhibit mycelial growth of the phytopathogenic Fusarium culmorum strain. These polymers exhibit various bioactive properties and have potential applications in many areas of human life.

Immunoisolated cells hold great promise for advancing cell therapeutics; however, their long-term storage remains a critical challenge due to ice formation and mechanical damage to both cells and the encapsulating matrix during cryopreservation. In this study, a cryo-fracture-resistant composite microcapsule has been developed using microfluidic technology, where sodium alginate was reinforced with cellulose nanocrystals (CNCs). The composite microcapsules were assessed for their ability to provide structural, mechanical, morphological, chemical, and thermal stability during cryopreservation. Additionally, red blood cells (RBCs) were used as a model to evaluate the ability of the optimized microcapsules to improve cell viability post-thaw. Results revealed that the microfluidic system allowed for precise control over microcapsule size and uniformity, which is crucial for even freezing and thawing. CNCs reinforced microcapsules exhibited delayed ice formation, improved ice recrystallization inhibition, and superior protection against freeze-induced deformations. Furthermore, the composite microcapsules enhanced post-thaw recovery of encapsulated RBCs and enabled the incorporation of a biocompatible cryoprotectant (trehalose). This study demonstrates a novel approach to optimizing cryopreservation techniques by leveraging the enhanced properties of composite microcapsules to mitigate cryo-injury and improve the functional recovery of encapsulated cells. These findings present a promising strategy for advancing microencapsulation-based cell therapies and broader biomedical applications.

Advanced wound care dressings are essential for improving clinical outcomes. The present study investigates the wound management potential of a unique dressing fabricated from silk proteins. The dressing was characterized for its physical and structural properties, including surface texture, porosity, fluid absorption capacity, and moisture vapor transmission rate. These parameters have been found to be critical for optimal wound healing. In vivo full thickness wound healing studies in a rat model validated the efficacy of the Silk-dressing compared to conventional cotton gauze and commercial polyurethane foam dressings. Histopathological analysis confirmed improved re-epithelialization, collagen deposition, angiogenesis, and formation of secondary follicles. Key advantages of Silk-dressing included non-adherence, absorption of exudate, maintenance of optimal moisture at wound site and accelerated wound closure. Biocompatibility studies were also conducted in accordance with ISO 10993 guidelines, demonstrating no cytotoxicity, irritation, sensitization, or pyrogenicity. These findings highlight the potential of this uniquely designed Silk-dressing as a superior alternative for wound management, with a potential to improve clinical outcomes.