Advanced Therapeutics最新文献

Intra-articular viscosupplementation with hyaluronic acid-based injections in osteoarthritic joints provides temporary symptomatic relief but requires multiple doses, causing discomfort and higher costs. A smart dual-functional hydrogel enhancing drug delivery and cartilage regeneration is a promising alternative. In this study, we fabricated an intra-articular Chitosan-PVA hydrogel ingrained with gallic acid-loaded amino-functionalized mesoporous silica nanoparticles (AF-MSNs). Cytotoxicity analysis using MG-63 cell lines confirmed its non-toxic nature, supporting its use in experimental models. The hydrogel combination can be effectively injected into the knee joint in collagenase-induced osteoarthritic high-fat diet (HFD) female Wistar rats. qRT-PCR analysis revealed a substantial decrease in the gene expression levels of MMP-9 and MMP-13, the catabolic enzymes involved in cartilage degeneration, in Ch-PVA hydrogel + AF-MSNs/GA treated IL-1β induced rat chondrocyte cells. Behavioral studies provided evidence of pain alleviation in the experimental animals, as demonstrated by improvements in both the knee bend test and gait scoring. Histomorphological analysis of the articular cartilage revealed a significant improvement in the rebuilding of the cartilage matrix and a substantial increase (p < 0.001) in the sulfated glycosaminoglycan (sGAG) contents. These findings underscore the therapeutic value of intra-articular administration of Ch-PVA hydrogel, enabling the sustained release of gallic acid from AF-MSNs in a rat model of osteoarthritis. The treatment effectively promotes extracellular matrix (ECM) synthesis and facilitates cartilage matrix regeneration, supporting its potential as a disease-modifying strategy for osteoarthritis.

Mucoadhesion is an effective approach for increasing the retention time of topical ophthalmic therapeutics, particularly in dry eye, as it may mitigate rapid nasolacrimal drainage and improve their limited bioavailability. Using the gelation properties of mucin, the major glycoprotein of the mucosa, to assemble drug loaded nanocarriers that would consolidate considerably on the ocular mucosa and facilitate sustained release is a facile approach to integrate mucoadhesion into topical formulations. However, mucin-based nanoparticles tend to aggregate due to their limited stability in colloidal solution form. This study reports on the synthesis and stabilization of mucin in nanoparticle form using alginate as an electrostatic stabilizer, and then the subsequent loading of antioxidant coenzyme Q10. Simultaneous ionotropic gelation of both alginate and mucin is employed to obtain self-assembling polymeric nanocarriers with superior mucoadhesive properties (>80% adheres to the ocular mucosa for 0.25 gm formulation), improved shelf stability, and desired shear-thinning behavior whereas coenzyme Q10 was encapsulated with high encapsulation efficiency (>96%) and sustained release for up to 4 days. Extensive in vivo assessment reveals the efficacy of the nanocarriers in improving dry eye symptoms. This study demonstrates a novel and straightforward way to synthesize stabilized alginate-mucin nanoparticles for the effective delivery of coenzyme Q10.

Transient bioresorbable systems operate only during the clinically indicated window and then dissolve into benign products, eliminating explantation. By matching device presence to the days to weeks period after surgery or intervention, they reduce exposure to anesthesia, reentry trauma, and risks of infection, bleeding, and wound dehiscence, while shortening recovery and lowering costs. This review surveys sensing and therapeutic platforms that use bioresorbable polymers, metals, and silicon based materials to provide structural, conductive, dielectric, and semiconducting functions. Physical sensing of pressure and temperature employs capacitive, piezoelectric, triboelectric, and resistive transduction, together with passive inductor capacitor resonant readouts. Chemical sensing of potential of hydrogen leverages fluorescence based optics, radio frequency hydrogel resonators, and ultrasound readable shape adaptive materials. Therapeutic examples include radio frequency or ultrasound powered electrical stimulation for nerve regeneration or analgesia, temporary cardiac pacing, and localized drug delivery via wireless heating reservoirs or sealed on demand valves. We present a design map linking material chemistry, thickness and geometry, and encapsulation to service lifetime, supported by accelerated soak tests and diffusion and Arrhenius models of defect driven leakage. We also offer cross modal rules and checklists for translational readiness, including standardized reporting and validation from models to living organisms.

Antibiotic abuse has given rise to bacterial resistance, which severely challenges the medical and public health domains. Distinct from traditional antibiotic sterilization methods, photodynamic sterilization has attracted significant attention due to its advantages of repeatable application, broad sterilization range, and multiple action targets. Therefore, zinc phthalocyanine 4-phenoxyacetate encapsulated in poly(lactic-co-glycolic acid) (PLGA@ZPCC NPs) is synthesized in this study, and explored their bactericidal efficacy via photodynamic therapy (PDT). The physicochemical properties and singlet oxygen generation capacity of PLGA@ZPCC NPs are analyzed via NMR, EA, TEM, DLS, FTIR, and ESR. Photodynamic antibacterial experiments demonstrated that the PLGA@ZPCC NPsr exhibited favorable bactericidal effects and satisfactory biocompatibility. In a mouse skin wound infection model, PLGA@ZPCC NPs showed a notable advantage in promoting wound healing. Specifically, the healing outcomes of the medium and high-dose (100, 250 mg/kg) of PLGA@ZPCC NPs are superior to the mupirocin (200 mg/kg). During the monitoring period, the mice showed no abnormal signs, such as impaired immune function or reduced body weight. Hematological routine tests and pathological examination indicated that PLGA@ZPCC NPs caused no significant damage or pathological alterations to the mice's major organ tissues. PLGA@ZPCC NPs exhibited excellent antibacterial activity, wound healing promotion, and biosafety.

Platinum nanoparticles (Pt NPs) possess unique redox activity, chemical stability, and enzyme-mimetic properties, making them promising candidates for anti-inflammatory and analgesic therapies; however, protein-based green encapsulation strategies for such applications remain largely unexplored. In this study, we report the biochemically assisted synthesis of Aloe vera protein-encapsulated platinum nanoparticles (APPt NPs) using sodium borohydride as the reducing agent and freshly extracted Aloe vera proteins as both stabilizing and capping agents. The formation of Pt NPs was confirmed by a characteristic colour change and validated through physicochemical characterization. X-ray diffraction revealed a face-centred cubic crystalline structure, UV–visible spectroscopy showed absorption in the 220–280 nm range due to surface plasmon resonance, and FTIR analysis confirmed the presence of protein functional groups on the nanoparticle surface. APPt NPs demonstrated significant biological efficacy. In vitro assays showed inhibition of protein denaturation (IC₅₀ = 44.52 µg/mL) and strong free-radical scavenging activity (IC₅₀ = 10.39 µg/mL). In vivo studies revealed ∼60% analgesic efficacy at 50 mg kg⁻¹ in the hot-plate model and ∼50% inhibition of carrageenan-induced paw edema after 4 h, outperforming the standard drug. These results collectively highlight APPt NPs as a biocompatible, redox-active nanotherapeutic candidate for managing pain and inflammation.

Osteoarthritis (OA) treatment faces critical challenges of rapid clearance and short therapeutic duration following conventional intra-articular (IA) drug injections. To address these limitations, researchers have developed novel carrier-based delivery systems that enable precise drug localization and sustained release through material engineering and controlled-release technologies. These innovative strategies significantly enhance drug retention within the joint cavity while reducing systemic exposure and associated side effects. This review systematically summarizes recent advancements in IA delivery systems, with a focus on the design principles of different carriers, as well as their applications in improving therapeutic outcomes. By providing a comprehensive analysis of the current research landscape, this review establishes a theoretical foundation for developing more effective OA treatment strategies.

Cancer is one of the major diseases threatening human health and life, and the development of cancer treatment methods is crucial for patient prognosis. Virus-mimicking nanoparticles (VMNs) are drug delivery nanocarriers inspired by viruses, characterized by good biocompatibility, excellent in vivo stability, high cellular uptake efficiency, and significant tumor accumulation. VMNs mimic the mechanism of viral infection of host cells to achieve precise drug release, holding great potential in overcoming the limitations of traditional cancer treatment methods. This article discusses the preparation strategies of VMNs, their functionalities, and cancer treatment methods based on VMNs, including oxidative therapy, immunotherapy, and heat therapy, and explores the future development trends of VMNs.

Tuberculosis (TB) remains a global health concern, primarily due to the alarming increase in multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) in recent years. To effectively overcome Mtb drug resistance mechanisms, innovative therapeutic modalities such as combinatorial therapy, which integrates conventional anti-tubercular drugs with antimicrobial peptides (AMPs), are being actively investigated. In this review, we have attempted to establish the therapeutic rationale for proposing membrane-targeting synthetic AMPs by focusing on the unique lipid composition and structural rigidity of the Mtb cell envelope. Subsequently, we evaluated the properties and molecular mechanisms of action of five key synthetic AMPs demonstrating potent antimicrobial activity against MDR and XDR strains of Mtb, which includes LLAP (a 15-amino-acid LL-37 analogue); CP26 (a 26-amino-acid cecropin A / mellitin hybrid); D-LAK120 (a 27-amino-acid containing synthetic AMP); hLF1-11/ hLF1-1117-30 (an 11-amino-acid human lactoferrin derivative); and MIAP (a 19-amino-acid magainin derivative). A detailed comparative analysis on synthetic peptides' physicochemical properties, efficacy, safety profile, pharmacodynamic characteristics and mechanisms of action are addressed. Finally, we have reported the significant translational challenges associated with the clinical application of synthetic AMPs, including systemic delivery and stability. Based on these systematic analysis, we put forth that synthetic AMPs, when utilized in combination with existing drugs, represent a highly promising therapeutic modality for overcoming drug-resistant tuberculosis infection.