Externally triggered drug delivery systems empower patients or healthcare providers to utilize external stimuli to initiate drug release from implanted systems. This approach holds significant potential for clinical disease management, offering appealing features like enhanced patient adherence through the elimination of needles and medication reminders. Additionally, it facilitates personalized medicine by granting patients control over the timing, dosage, and duration of drug release. Moreover, it enables precise drug delivery to targeted locations where external stimuli are applied. Advances in materials science, nanotechnology, chemistry, and biology have been pivotal in driving the development of these systems. This review presents an overview of the progress in research on drug release systems responsive to external stimuli, such as light, ultrasound, magnetic fields, and temperature. It discusses the construction strategies of externally triggered drug delivery systems, the mechanisms governing triggered drug release, and their applications in disease management.
Improving the degradation performance and enhancing the biocompatibility are the main challenges of Mg-based biodegradable implants. In this study, a nano-hydroxyapatite-enhanced (nHA) Mg matrix composite was fabricated via friction stir processing and characterised, including microstructure, mechanical, in vitro degradation properties, and cytocompatibility. Hydroxyapatite is renowned for its superior bone compatibility, promoting healing responses and tissue growth. Friction stirring created a gradient grain structure in the alloy, with the stir zone exhibiting the highest grain refinement. The stir zone also contained most of the incorporated nHA and exhibited a strong texture with grains preferentially oriented along the [0001] direction. Immersion and polarisation experiments showed an increase in the FSPed WE43-nHA's corrosion resistance due to the refined microstructure. The treatment also caused a shift in the corrosion mode of the alloy from localized to uniform corrosion despite some localized corrosion associated with the nHA. Cytocompatibility tests in human osteoblast (HOB) cell lines indicated good biocompatibility in the Mg-nHA alloy, with cells exhibiting relatively healthy morphology and increased live cell count. Friction stir processing is a viable manufacturing option for creating Mg-based metal matrix composites with improved corrosion resistance and good biocompatibility.
Valvular heart disease (VHD) is a significant public health threat, with heart valve replacement surgery being the standard treatment for severe cases. Despite of advancements in artificial heart valves, their longevity remains limited due to in vivo degeneration. In consequence, there is an urgent need for effective methods to enhance the durability of artificial heart valves. Because oxidative stress (OS) is a key driving factor contributing to the failure of cardiovascular implants, this review focuses on how OS plays a critical role in heart valve degeneration, and its relationship with four major physiological mechanisms: extracellular matrix (ECM) degradation, immune response, thrombosis and lipid metabolism. By highlighting OS as a potential therapeutic target, we explore surface modification strategies that incorporate these fundamental mechanisms, refer to passive approaches including OS elimination, immunosuppression, blocking surface-degradation active groups, and anticoagulation, and active approaches such as regulating biological function recovery, and surface endothelial remodeling. These strategies aim to delay or reverse artificial valves degeneration via combining with the perspective of OS regulation, ultimately extending the prognosis period after heart valve replacement surgeries.
Sepsis frequently leads to life-threatening organ failure due to an in appropriate response by the body to bacterial, viral, and fungal infections. In recent years, there has been an increasing interest in using nanoparticles to develop biomarkers and drug delivery systems that have significantly improved the treatment of infectious diseases. Herein, we update the most recent development of nanoparticle-based therapeutics for sepsis treatment. This article begins with a brief overview of how sepsis is triggered and its associated diseases. It also explores the differences between traditional and modern treatment approaches. Afterward, the reasons for embracing nanotechnology-based therapies for sepsis are summarized, including their ability to reduce inflammation, provide antioxidant effects, regulate cell signaling pathways, manage reactive oxygen and nitrogen species (RONS) production, control autophagy and apoptosis, clear lipopolysaccharides (LPS) from the blood, inhibits the formation of cell-free DNA and cytokine storms. Furthermore, the special emphasis is on updating the use of nanotechnology-mediated drug delivery systems, such as nanoparticles, liposomes, and exosomes, in the treatment of sepsis caused by various microorganisms. Moreover, we also discuss polymer mediated therapy and some dynamic therapeutic aspects in septecemia disease. In addition, the article highlights the challenges and a limitation associated with using drug delivery for sepsis treatment and expresses the hope that this review will accelerate the development of more effective sepsis therapies and facilitate the transition from research to practical clinical application.
Prodrug nanoparticles have been explored as an effective means for drug delivery because of controlled drug release in a stimulus-responsive manner. Organellar-targeted drug delivery could enhance the efficacy of cancer therapy. Herein, pH and light dual responsive mitochondrial targeted prodrug nanoparticles were designed to deliver both chemotherapeutic drugs and photosensitisers for enhanced antitumour efficacy. The prodrug nanoparticles (TPP-PEI-PheoA/ALG=DOX NPs, TPPAD NPs) are composed of a light-responsive mitochondrial targeted prodrug (triphenylphosphonium and pheophorbide A modified polyethyleneimine, TPP-PEI-PheoA) and a pH-responsive prodrug (doxorubicin conjugated alginate with Schiff's base bond, ALG=DOX). TPPAD NPs were prepared through electrostatic interaction. TPPAD NPs could simultaneously deliver DOX and PheoA to the tumour site by passive targeting effect, release drugs in a designed mode and deliver drugs to the target organelles. Moreover, TPPAD NP-based PDT could induce immunogenic cell death of tumour cells, thereby activating the immune system. TPPAD NPs greatly enhanced antitumour efficacy by combinational therapy. Taken together, this prodrug nanoparticle platform has appeared to be a simple and smart nanomedicine for targeted tumour combinational treatment.
Acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), is the major cause of intensive care unit death worldwide. ALI/ARDS is a common condition characterized by a storm of potent inflammatory cytokines. Lung delivery of glucocorticoids (GCs) by inhalation is a potential approach for ALI treatment and ARDS prevention; however, its efficacy is limited by the rapid clearance of GCs in lungs. In this study, we developed surface-modified poly(lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with bioadhesive properties for local delivery to the epidermis of lung tissues, which exhibited prolonged release profile of payloads following intratracheal spraying administration. Compared with that of non-adhesive nanoparticles (NNPs), BNPs showed significantly enhanced adhesion and prolonged retention within lung tissues in vivo. Lipopolysaccharide (LPS)-induced ALI mice treated with betamethasone dipropionate (BD)-loaded BNPs showed significantly fewer lung histological alterations and less lung inflammation than those administered free BD or BD-loaded NNPs, indicating the enhanced therapeutic efficacy of BD/BNPs in ALI. In contrast, the features of ARDS were observed in the animal models without any treatments. Our findings demonstrated that pulmonary delivery of BNPs can maintain their same surface structures and continuously form covalent connections with the contacted tissues, emphasizing their potential to improve the therapeutic efficacy in ALI and prevent from ARDS.
Diabetes mellitus (DM) is a chronic metabolic disorder that can affect the balance of bone metabolism and bone microenvironment, leading to impaired fracture healing. There are several underlying mechanisms which contributing to the impaired diabetic bone microenvironment such as hyperglycemia, the production of advanced glycation end products (AGEs), inflammation, and oxidative stress, etc. Recent studies have achieved great progress in developing novel smart biomaterials in improving the diabetic bone microenvironment to promote diabetic fracture healing. In this paper, we reviewed the mechanisms on DM-induced impaired fracture healing. Meanwhile, we also summarized the smart biomaterials used to improve the local microenvironment of diabetic fractures healing, which provides a novel perspective for the future treatment of fractures in diabetic patients.
Macroporous cryogel has the advantages of nutrient exchange and cell growth, and is an ideal material for tissue regeneration. In order to strengthen the machenical properties of cryogel for the widely use, a high strength gelatin/sodium alginate/nano hydroxyapatite (nHA) porous cryogel (GA-HA cryogel) was prepared by a simple freeze-thaw process. The mechanical strength of GA-HA cryogel increased significantly with the increase of nHA content. In vitro studies showed that GA-HA cryogel had good biocompatibility and no obvious cytotoxicity to MC3T3-E1 cells. The results of alkaline phosphatase activity assay and osteocalcin immunofluorescence staining showed that GA-HA1 porous hydrogel system could significantly increase the expression of MC3T3-E1 alkaline phosphatase and osteocalcin when the content of nHA was 1 %. In addition, porous GA-HA cryogel showed good performance in promoting bone regeneration in rat skull defect model. Therefore, the high-strength double network cryogel prepared in this study can provide new applications in bone repair and tissue regeneration.