Multifunctional composite soluble microneedle patch based on "one stone, three birds" strategy for promoting the healing of infectious wounds.

The colonisation of microorganisms such as bacteria forms a biofilm barrier on the wound's surface, preventing or delaying the penetration of antibacterial drugs. At the same time, continuous bacterial infection can cause oxidative stress and an inflammatory response and hinder angiogenesis, resulting in difficult wound healing. Based on the "one stone, three birds" strategy, a multi-functional nanoparticle composite soluble microneedle was designed and developed to solve this dilemma better. Ginsenoside-liposomes(R-Lipo) were prepared by ginsenoside Rg3, which had the effect of promoting repair, instead of cholesterol, and loaded with berberine (Ber), the antibacterial component of Coptis, together with polydopamine (PDA), which had anti-inflammatory and antioxidant properties, into microneedles based on hyaluronic acid (PDA/R-Lipo@BerMN). PDA/R-Lipo@BerMN tip can penetrate and destroy the integrity of the biofilm, dissolve under the action of hyaluronidase in the skin, and gradually release the drug to achieve rapid antibacterial, anti-inflammatory, antioxidant, and proliferation. As expected, the PDA/R-Lipo@BerMN patch effectively cleared ROS during wound closure, further promoted M2 macrophage polarisation, eradicated bacterial infection, and regulated the immune microenvironment, promoting inflammation suppression, collagen deposition, angiogenesis, and tissue regeneration.

Inflammatory macrophage reprogramming strategy of fucoidan microneedles-mediated ROS-responsive polymers for rheumatoid arthritis.

During the pathogenesis of rheumatoid arthritis, inflammatory cells usually infiltrate synovial tissues, notably, M1-type macrophages, whose redox imbalance leads to the degradation of joint structures and deterioration of function. Natural active products play a vital role in immune modulation and antioxidants. In this study, we constructed a ROS-responsive nanoparticle called FTL@SIN, which consists of fucoidan (Fuc) and luteolin (Lut) connected by a ROS-responsive bond, Thioketal (TK), and encapsulated with an anti-rheumatic drug, Sinomenine (SIN), for synergistic anti-inflammatory effects. The FTL@SIN is then dispersed in high molecular weight Fuc-fabricated dissolvable microneedles (FTL@SIN MNs) for local administration. Therapy of FTL@SIN MNs afforded a significant decrease in macrophage inflammation while decreasing key pro-inflammatory cytokines and repolarizing M1 type to M2 type, thereby ameliorating synovial inflammation, and promoting cartilage repair. Additionally, our investigations have revealed that Fucoidan (Fuc) demonstrates synergistic effects, exhibiting superior mechanical strength and enhanced physical stability when compared to microneedles formulated solely with hyaluronic acid. This study combines nanomedicine with traditional Chinese medicine, a novel drug delivery strategy that presents a promising avenue for therapeutic intervention in rheumatoid arthritis.

Marine polysaccharides: Biological activities and applications in drug delivery systems.

The ocean is the common home of a large number of marine organisms, including plants, animals, and microorganisms. Researchers can extract thousands of important bioactive components from the oceans and use them extensively to treat and prevent diseases. In contrast, marine polysaccharide macromolecules such as alginate, carrageenan, Laminarin, fucoidan, chitosan, and hyaluronic acid have excellent physicochemical properties, good biocompatibility, and high bioactivity, which ensures their wide applications and strong therapeutic potentials in drug delivery. Drug delivery systems (DDS) based on marine polysaccharides and modified marine polysaccharide molecules have emerged as an innovative technology for controlling drug distribution on temporal, spatial, and dosage scales. They can detect and respond to external stimuli such as pH, temperature, and electric fields. These properties have led to their wide application in the design of novel drug delivery systems such as hydrogels, polymeric micelles, liposomes, microneedles, microspheres, etc. In addition, marine polysaccharide-based DDS not only have smart response properties but also can combine with the unique biological properties of the marine polysaccharide base to exert synergistic therapeutic effects. The biological activities of marine polysaccharides and the design of marine polysaccharide-based DDS are reviewed. Marine polysaccharide-based responsive DDS are expected to provide new strategies and solutions for disease treatment.

Resveratrol nanocrystals based dissolving microneedles with highly efficient for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common immune disease characterized mainly by erosive arthritis with extensive clinical sequelae. Resveratrol (Res) has pharmacological effects in the treatment of RA, but it has not been widely used in the clinic due to its poor water solubility and low bioavailability. In this study, a drug delivery system (Res-NC MNs) of dissolved microneedles (MNs) loaded with Res nanocrystals (NC) was designed for the treatment of RA. Res-NC MNs can improve the drawbacks of long-term oral drug delivery with toxic side effects and low compliance associated with intra-articular drug delivery. In this study, Res-NC was prepared by media milling and loaded into soluble microneedles prepared from hyaluronic acid (HA) by vacuum casting for the treatment of RA. HA has high mechanical strength and can penetrate the cuticle layer of the skin for effective drug delivery. In in vivo pharmacodynamic experiments, Res-NC MNs achieved better therapeutic efficacy in the treatment of RA compared with oral Res. These findings suggest that Res-NC MNs may be an effective and promising drug delivery strategy for the treatment of RA.

Plant exosome nanovesicles (PENs): green delivery platforms.

Natural plants have been attracting increasing attention in biomedical research due to their numerous benefits. Plant exosome-derived vesicles, some of the plant's components, are small nanoscale vesicles secreted by plant cells. These vesicles are rich in bioactive substances and play significant roles in intercellular communication, information transfer, and maintaining homeostasis in organisms. They also hold promise for treating diseases, and their vesicular structures make them suitable carriers for drug delivery, with large-scale production feasible. Therefore, this paper aims to provide an overview of nanovesicles from different plant sources and their extraction methods. We also outline the biological activities of nanovesicles, including their anti-inflammatory, anti-viral, and anti-tumor properties, and systematically introduce their applications in drug delivery. These applications include transdermal delivery, targeted drug delivery, gene delivery, and their potential use in the modern food industry. This review provides new ideas and methods for future research on plant exosomes, including their empowerment by artificial intelligence and gene editing, as well as their potential application in the biomedicine, food, and agriculture industries.

Novel pH-responsive E-selectin targeting natural polysaccharides hybrid micelles for diabetic nephropathy.

Diabetic nephropathy (DN) is an important complication of diabetes and is the main cause of end-stage renal disease. The pathogenesis of DN is complex, including glucose and lipid metabolism disorder, inflammation, and so on. Novel hybrid micelles loaded Puerarin (Pue) based on Angelica sinensis polysaccharides (ASP) and Astragalus polysaccharide (APS) were fabricated with pH-responsive ASP-hydrazone-ibuprofen (BF) materials (ASP-HZ-BF, SHB) and sialic acid (SA) modified APS-hydrazone-ibuprofen materials (SA/APS-HZ-BF, SPHB) by thin-film dispersion method. The SA in hybrid micelles can specifically bind to the E-selectin receptor which is highly expressed in inflammatory vascular endothelial cells. The loaded Pue could be accurately delivered to the inflammatory site of the kidney in response to the low pH microenvironment. Overall, this study provides a promising strategy for developing hybrid micelles based on natural polysaccharides for the treatment of diabetic nephropathy by inhibiting renal inflammatory reactions, and antioxidant stress.

Novel dual CAFs and tumour cell targeting pH and ROS dual sensitive micelles for targeting delivery of paclitaxel to liver cancer.

Tumour development is not only an independent event of genetic mutation and overgrowth of tumour cells but is the result of a synergistic interaction between a malignant tumour and its surrounding tumour stromal microenvironment. In this paper, we address the shortcomings of current tumour therapy by focussing on the tumour itself and the surrounding microenvironment to achieve a two-pronged targeting model. In this paper, a dual-targeting, pH/reactive oxygen species (ROS) sensitive nano-drug delivery system for tumour cells and CAFs was designed. A hyaluronic acid (HA) with CD44 receptor targeting on the surface of tumour cells was selected as the main carrier material, and a dipeptide Z-glycine-proline (ZGP) with specific targeting of fibroblast activating protein (FAP) on the surface of CAFs was modified on HA to achieve precise targeting of CAFs, open the physical barrier of tumour cells and improve the deep penetration effect of the tumour, while introducing thioketone bond and ketone condensation bond to take advantage of the highly reactive ROS and low pH microenvironment at the tumour site to achieve chemical bond breaking of nano micelles encapsulating paclitaxel (PTX), drug release, and thus drug aggregation at the tumour site and improved bioavailability of the drug.

Achyranthes polysaccharide based dual-responsive nano-delivery system for treatment of rheumatoid arthritis.

Achyranthes plays the role of dredging the meridians and clearing the joints with a certain anti-inflammatory effect, peripheral analgesic activity and central analgesic activity. A novel self-assembled nanoparticles containing Celastrol (Cel) with matrix metalloproteinase (MMP)-sensitive chemotherapy-sonodynamic therapy was fabricated targeting macrophages at the inflammatory site of rheumatoid arthritis. Dextran sulfate (DS) with highly expressed SR-A receptor on the surface of macrophages is used to specifically target the site of inflammation; by introducing PVGLIG enzyme-sensitive polypeptides and ROS-responsive bonds, it can achieve the desired effect on MMP-2/9 and reactive oxygen species at the joint site. The preparation forms DS-PVGLIG-Cel&Abps-thioketal-Cur@Cel nanomicelles, referred to as D&A@Cel. The resulting micelles had an average size of 204.8 nm and the zeta potential -16.46 mV. The results show that activated macrophages can effectively capture Cel in in vivo experiments, indicating that Cel delivered by nanoparticles can significantly improve bioavailability.

Multifunctional nanoparticles with anti-inflammatory effect for improving metabolic syndromes.

Metabolic syndromes are a group of metabolic disorders for which the molecular mechanisms are still unclear. An increasing number of studies have implicated metabolic syndrome in the association with inflammation. Currently, lipsomes is known to improve nanoparticle hydrophobicity. Meanwhile, in drug delivery systems the application of cholesterol, which is commonly used to stabilise liposomal structures, has essentially no pharmacological effect on liposomes. Herein, we developed an 'anti-inflammatory liposome' (Phy-Lip) to effectively handle these challenges via employing Phytosterol instead of cholesterol. Different with the conventional liposomes, Phy-Lip is a much more brilliant nanoparticle with anti-inflammatory functions. In Phy-Lip, cholesterol was substituted by Phy, which works as membrane stabiliser, anti-inflammatory adjuvant at the same time. The experimental results show that Phy-Lip has a strong anti-inflammatory effect, and improves Metabolic syndromes. This study aims to provide a way to solve the challenge.

CD44 Receptor-Targeted and Reactive Oxygen Species-Responsive H2S Donor Micelles Based on Hyaluronic Acid for the Therapy of Renal Ischemia/Reperfusion Injury.

For the therapy attenuating renal ischemia-reperfusion (IR) injury, a novel drug delivery system was urgently needed, which could precisely deliver drugs to the pathological renal tissue. Here, we have prepared new nanomaterials with a reactive oxygen species (ROS)-responsive hydrogen sulfide (H2S) donor and hyaluronic acid that targets CD44 receptor. The novel material was synthesized and characterized via related experiments. Then, rapamycin was loaded, which inhibited kidney damage. In the in vitro study, we found that the micelles had ROS-responsiveness, biocompatibility, and cell penetration. In addition, the experimental results showed that the intracellular H2S concentration after administration was threefold higher than that of the control group. The western blot assay revealed that they have anti-inflammatory effects via H2S donor blocking the NF-κB signaling pathway. Consequently, the rising CD44 receptor-targeting and ROS-sensitive H2S donor micelles would provide a promising way for renal IR injury. This work provides a strategy for improving ischemia/reperfusion injury for pharmaceuticals.

A novel saponin liposomes based on the couplet medicines of Platycodon grandiflorum-Glycyrrhiza uralensis for targeting lung cancer.

Liposomes have been widely used for targeted drug delivery, but the disadvantages caused by cholesterol limit the application of conventional liposomes in cancer treatment. The compatibility basis of couplet medicines and the compatibility principle of the traditional Chinese medicine principle of 'monarch, minister, assistant and guide' are the important theoretical basis of Chinese medicine in the treatment of tumor and the important method to solve the problem of high toxicity. In this study, the active ingredients of the couplet medicines Platycodon grandiflorum and Glycyrrhiza uralensis were innovatively utilized, and glycyrrhizic acid (GA) was encapsulated in liposomes constructed by mixing saponin and lecithin, and cholesterol was replaced by platycodin and ginsenoside to construct saponin liposomes (RP-lipo) for the drug delivery system of Chinese medicine. Compared with conventional liposomes, PR-lipo@GA has no significant difference in morphological characteristics and drug release behavior, and also shows stronger targeting of lung cancer cells and anti-tumor ability in vitro, which may be related to the pharmacological properties of saponins themselves. Thus, PR-lipo@GA not only innovatively challenges the status of cholesterol as a liposome component, but also provides another innovative potential system with multiple functions for the clinical application of TCM couplet medicines.

Novel multifunctional bionanoparticles modified with sialic acid for stroke treatment.

Oxidative stress and inflammation are two key pathophysiological mechanisms that lead to neuronal apoptosis and brain damage following ischemia/reperfusion (I/R) injury. Because of their complex pathological mechanisms and the presence of the blood-brain barrier, the treatment of I/R is severely limited. Inspired by the fact that Macrophage membranes (MM) can cross the blood-brain barrier, we have developed a new multifunctional bionic particle (MSAOR@Cur). The modification of Sialic acid (SA) on the surface of Angelica polysaccharides (APS), the attachment of Resveratrol (Res) using the ROS-responsive bond oxalate bond as a linker arm, constitutes amphiphilic nanoparticles with an inner core encapsulated with curcumin (SAOR@Cur), and finally the use of MM camouflage to integrate the neuroprotection of APS, the free radical scavenging of Res, and the anti-inflammation of curcumin (Cur) in one strategy. Interestingly, the experimental results show that MSAOR@Cur can successfully deliver curcumin to the area of ischemia-reperfusion injury.

N-acetylneuraminic acid and chondroitin sulfate modified nanomicelles with ROS-sensitive H2S donor via targeting E-selectin receptor and CD44 receptor for the efficient therapy of atherosclerosis.

Currently, very limited therapeutic approaches are available for the drug treatment of atherosclerosis(AS). H2S-donor is becoming a common trend in much life-threatening research. Several studies have documented that H2S-lyase is predominantly present in endothelial cells. N-Acetylneuraminic acid (SA), natural carbohydrate, binds specifically to the E-selectin receptor of endothelial cells. Meanwhile, recent studies related to Chondroitin sulfate have excellent target binding ability with CD44 receptor. We conjecture that the N-Acetylneuraminic acid and Chondroitin sulfate modified nanomicelles not only enhances the accumulation of the drug but also cleaves the H2S donor in the lesion, thus one stone two birds. Given these findings, we synthesized two kinds of nanoparticles, Carrier I (SCCF) and Carrier II (SCTM), for atherosclerosis to validate our guesses. Initially, S-allyl-L-cysteine and 4-methoxyphenylthiourea were used as H2S donors for SCCF and SCTM, respectively. After the introduction of ROS-sensitive groups. Then, micelles with N-Acetylneuraminic acid and Chondroitin sulfate were prepared to load rapamycin(RAP). Further, in atherosclerosis Oil Red O staining (ORO) results confirmed remarkable treatment effect with SCCF@RAP and SCTM@RAP. Thus, we conclude that the effect of dual-targeting nanomicelles with ROS-sensitive H2S donor based on N-Acetylneuraminic acid and Chondroitin sulfate will have a better role in atherosclerosis.

Construction of bionanoparticles based on Angelica polysaccharides for the treatment of stroke.

Ischemic stroke is an acute and severe neurological disease, resulting in disability and death. The poor drug delivery to cerebral ischemic regions is a key challenge of ischemic stroke treatment. Inspired by the ability of Macrophage membranes to cross the blood-brain barrier, We prepared amphiphilic nanoparticles (AOE@TMP) by linking Angelica polysaccharide (APS) and Ethyl ferulate (EF) using oxalate bond (OL) as the linker arm, with an inner core encapsulated with Tetramethylpyrazine (TMP), and finally using macrophage membrane camouflage (MAOE@TMP). The experimental results show that MAOE@TMP can successfully deliver drugs to the site of brain injury and specifically release it in the microenvironment of the brain injury site, and the three active ingredients in the herb pair could potentiate and significantly reduce the cerebral infarction size.