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1.
    
Novel dual physically cross-linked (DPC) hydrogels with great tensile strength, ultrahigh elongation, and promising repairability are designed by introducing cellulose nanocrystal (CNC) or hydrophobized CNC (CNC-C8) into polymers physically cross-linked by hydrophobic forces. C18 alkyl chain is grafted to N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) for hydrophobic monomer (DMAPMA-C18), and C8 to CNC surface for hydrophobic CNC (CNC-C8). CNC-C8 (or CNC) DPC hydrogels are synthesized, with monomers N,N-dimethylacrylamide (DMAc) and DMAPMA-C18 polymerized to form the first network physically cross-linked by hydrophobic interactions, on which the secondary cross-linking points are formed by hydrophobic interactions between CNC-C8 and DMAPMA-C18, electrostatic interactions between CNC-C8 (or CNC) and DMAPMA, as well as hydrogen bonding between CNC-C8 (or CNC) and DMAc. Compared with optimum CNC DPC hydrogels of the highest tensile strength (238 ± 8 kPa), the optimum CNC-C8 DPC hydrogel with 0.0675 w/v% DMAPMA-C18 and 0.4 w/v% CNC-C8 possesses stronger tensile strength of 331 ± 32 kPa and excellent elongation of 4268% ± 1446% as well, demonstrating the enhanced mechanical property of the hydrogel by introduced hydrophobic interactions. In addition, such DPC hydrogel can be facilely repaired with tetrahydrofuran (THF) on the cut surfaces while retaining good tensile stress and elongation behaviors.  相似文献   

2.
药物共晶是改善难溶性药物溶出与生物利用度有效的策略之一, 但其在溶出过程中容易发生相转变导致原料药重结晶, 失去增溶优势, 该问题已成为难溶性药物共晶应用的主要瓶颈之一。选择合适的添加剂能够有效抑制药物共晶溶出过程中的相转变, 提高难溶性药物共晶溶出与吸收程度; 此外, 复杂的胃肠道给药环境与药物共晶体内吸收行为, 均会对药物共晶的生物利用度产生明显影响。因此, 本文总结了关于难溶性药物共晶溶出与吸收的研究进展, 期望为药物共晶制剂处方的开发提供指导。  相似文献   

3.
    
With the advancement of medical and digital technologies, smart skin adhesive patches have emerged as a key player for complex medical purposes. In particular, skin adhesive patches with integrated electronics have created an excellent platform for monitoring health conditions and intelligent medication. However, the efficient design of the adhesive patches is still challenging as it requires a strong combination of network structure, adhesion, physical properties, and biocompatibility. To design an assimilated device, one must have a deep knowledge of various skin adhesive patches. This article provides a comprehensive review of the recent advances in skin-adhesive patches, including hydrogel-based adhesive patches, transdermal patches, and electronic skin (E-skin) patches, for various biomedical applications such as wound healing, drug delivery, biosensing, and health monitoring. Furthermore, the key challenges, implementable strategies, and future designs that can potentially provide researchers in designing innovative multipurpose smart skin patches are discussed. These advanced approaches are promising for managing the health and fitness of patients who require regular medical care.  相似文献   

4.
    
Oral amiodarone for 3–6 months is commonly required for the prevention and treatment of atrial fibrillation (AF) after surgical ablation of refractory AF. However, clinical data show that oral administration is likely to cause systemic toxicity, especially pulmonary fibrosis. Here, a new strategy is described for the treatment and prevention of postsurgical AF via the epicardial application of a monolithic reservoir microneedle device. These findings demonstrate that this strategy enables a sustained transport of amiodarone directly to the atrium, thereby maximizing therapeutic efficacy and minimizing systemic drug distribution. Notably, a significantly reduced drug dosage (only one dose of 6.3 mg for reservoir MNs versus a daily dose of ≈10 mg for oral administration) achieves therapeutic efficacy over a long period of 24 weeks in a rat AF model, circumventing the risks of pulmonary fibrosis associated with oral administration. This device can serve as a promising alternative to oral amiodarone, providing a robust therapeutic strategy for the prevention and treatment of postsurgical AF is antipicated.  相似文献   

5.
    
A biocompatible and modifiable protein nanocarrier is a promising candidate for tumor targeted drug delivery. However, it is challenging to effectively load hydrophobic drugs, not to mention to upload both hydrophilic and hydrophobic drugs on one protein nanocarrier. Here, an amphiphilic multi-drug loading protein nanocage (Am-PNCage) is presented which is generated by replacing the fifth helix of human H-ferritin (HFn) subunit with a functional motif composed of hydrophobic–hydrophilic-RGD peptides. The Am-PNCage possesses a dual targeting property resulting from the intrinsic CD71 targeting ability of HFn and the integrin α vβ3 targeting ability of displayed RGD peptides. Through the hydrophilic drug entry channel in the protein nanocage and hydrophobic peptides displayed on the outer surface, amphiphilic epirubicin (132)/camptothecin (50) are stereoscopically loaded into the inner cavity/outer protein shell, respectively, for one Am-PNCage, exhibiting cascade drug release pattern. The dual-targeted Am-PNCage promotes the loaded drugs penetrating various 3D tumor models in vitro, as well as traversing the brain blood barrier and accumulating in brain tumors in vivo. Moreover, the drug loaded Am-PNCage shows reduced side effects and significantly enhances synergistic efficacy against brain tumor, metastatic liver cancers, and drug resistant breast tumor. Thus, the Am-PNCage represents a novel promising protein nanocarrier for targeted combination chemotherapy.  相似文献   

6.
    
Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch‐type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.  相似文献   

7.
    
Pain management during dental procedures is a cornerstone for successful daily practice. In current practice, the traditional needle and syringe injection is used to administer local anesthesia. However, the appearance of long needles and the pain associated with it often leads to dental anxiety deterring timely interventions. Microneedles (MNs) have emerged as a minimally invasive alternative to hypodermic needles and shown to be effective in transdermal drug delivery applications. In this article, the potential use of MNs for local anesthesia delivery in dentistry is explored. The development of a novel conductive MN array that can be used in combination with iontophoresis technique to achieve drug penetration through the oral mucosa and the underlying bone tissue is presented. The conductive MN array plays a dual-role, creating micro-conduits and lowering the resistance of the oral mucosa. The reduced tissue resistance further enhances the application of a low-voltage current that is able to direct and accelerate the drug molecules to target the sensory nerves supplying teeth. The successful delivery of lidocaine using this new strategy in a clinically relevant rabbit incisor model is shown to be as effective as the current gold standard.  相似文献   

8.
    
The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.  相似文献   

9.
    
Electrical stimulation (ES) is widely used in physiological and medical sciences, while its application to treat inflammatory skin diseases (ISDs) remains a challenge owing to their natural pathological cuticle barrier and lack of an effective combination with chemotherapy to achieve specific immunomodulation. Here, a wearable, battery-free, multi-component drug-loaded electronic microneedle (mD-eMN) system is developed by integrating remodeled metal microneedles loaded with multi-component chemical drugs and flexible triboelectric nanogenerators (TENGs). The system can rapidly release drugs into the site of ISDs and then realize an efficient penetration into cell body and specific immunomodulation under the synergism of pulsed electrons originating from the TENG. Also, the pulsed electrons can promote skin tissue homeostasis reconstruction to alleviate the inflammatory process of ISDs. Sufficient evidence shows that a significant skin inflammation regression of psoriasis (a typical ISDs model) is achieved using the mD-eMN system compared to traditional ES or chemotherapy alone. This innovative wearable mD-eMN system provides an effective flexible electronic and chemical drug joint technological platform for the treatment of ISDs, which is not only suitable for the treatment of psoriasis in this study but also maybe for other ISDs such as diabetic ulcers and skin tumors.  相似文献   

10.
    
To save bandwidth and storage space as well as speed up data transmission, people usually perform lossy compression on images. Although the JPEG standard is a simple and effective compression method, it usually introduces various visually unpleasing artifacts, especially the notorious blocking artifacts. In recent years, deep convolutional neural networks (CNNs) have seen remarkable development in compression artifacts reduction. Despite the excellent performance, most deep CNNs suffer from heavy computation due to very deep and wide architectures. In this paper, we propose an enhanced wide-activated residual network (EWARN) for efficient and accurate image deblocking. Specifically, we propose an enhanced wide-activated residual block (EWARB) as basic construction module. Our EWARB gives rise to larger activation width, better use of interdependencies among channels, and more informative and discriminative non-linearity activation features without more parameters than residual block (RB) and wide-activated residual block (WARB). Furthermore, we introduce an overlapping patches extraction and combination (OPEC) strategy into our network in a full convolution way, leading to large receptive field, enforced compatibility among adjacent blocks, and efficient deblocking. Extensive experiments demonstrate that our EWARN outperforms several state-of-the-art methods quantitatively and qualitatively with relatively small model size and less running time, achieving a good trade-off between performance and complexity.  相似文献   

11.
    
Traditional topical ointment applied on the skin surface has poor drug penetration due to the thickening of the stratum corneum for psoriasis. Microneedles (MNs) provide a desirable opportunity to promote drug penetration. However, the common MNs are difficult to meet the requirement of on-demand drug delivery. In this study, a smart electrical responsive MNs is fabricated by introducing conductive material of polypyrrole (PPy). Further, a self-powered controllable transdermal drug delivery system (sc-TDDS) based on piezoelectric nanogenerator (PENG) is developed. The sc-TDDS can control drug release by collecting and converting mechanical energy into electrical energy. The sc-TDDS can release 8.5 ng dexamethasone (Dex) subcutaneously per electrical stimulation. When treating psoriasis-like skin disease with sc-TDDS, the inflammatory skin returned to normal after 5 days, which is obviously better than treating with traditional Dex solution coating. This work provides a promising approach of on-demand transdermal drug release for various disease treatment scenarios.  相似文献   

12.
    
Accurate medical recordkeeping is important for personal and public health. Conventional forms of on-patient medical information, such as medical alert bracelets or finger-markings, may compromise patient privacy because they are readily visible to other people. Here, the development of an invisible, temporary, and easily deployable on-patient medical recordkeeping system is reported. Information is stored in unique patterns of spatially distributed near-infrared (NIR) fluorescent quantum dots (QDs), which are delivered to the skin using dissolvable microneedle arrays. The patterns are invisible to the naked eye but detectable with an infrared camera, which can extract information with >98% accuracy using automated pattern recognition software. By encapsulating NIR QDs in an FDA-approved biodegradable polymer, biodegradation rates can be tuned so that the encoded medical information can be conveyed in both a spatial and temporal manner, with some components fading within 100 days and others persisting for 6 months. This may be particularly useful for administering a series of vaccinations or treatments by indicating if enough time has passed for the patient to receive the next dose. Importantly, this system contains no personal information, does not require connection to a centralized database, and is not visible to the naked eye, ensuring patient privacy.  相似文献   

13.
    
Phototherapy represents an attractive route for treating a range of challenging dermatological diseases. Existing skin phototherapy modalities rely on direct UV illumination, although with limited efficacy in addressing disorders of deeper tissue and with requirements for specialized illumination equipment and masks to shield unaffected regions of the skin. This work introduces a skin-integrated optoelectronic device that incorporates an array of UVA (360 nm) light emitting diodes in layouts that match those of typical lesional plaques and in designs that couple to biocompatible, penetrating polymer microneedle light waveguides to provide optical access to deep skin. Monte Carlo simulations and experimental results in phantom skin suggest that these waveguides significantly enhance light delivery to deep skin, with a >4-fold increase for depths of >500 µm. In ex vivo human skin, the devices show reduced measures of phototoxicity compared to direct illumination and enhanced modulation of gene expression relevant to sclerosing skin diseases. These systems are also compatible with design principles in soft, skin-compatible electronics and battery-powered wireless operation. Collectively, the favorable mechanical and light delivery properties of these devices expand possibilities in targeting of deep skin lesions beyond those attainable with clinical-standard UV light therapy approaches.  相似文献   

14.
无定形态固体分散体能显著提高难溶性药物的溶解度和生物利用度, 但其在制备或储存过程中容易发生结晶而削弱原有的优势。固体分散体中的无定形态药物结晶过程分为成核和晶体生长两步, 其中成核是结晶的起始环节和关键步骤, 但目前尚对无定形态药物结晶成核认识还很有限。本文对无定形态药物成核的研究方法、成核理论、添加物影响成核的机制及成核影响因素进行归纳, 期望为无定形态固体分散体处方设计和提高其物理稳定性提供理论指导。  相似文献   

15.
    
A conductive engineered cardiac patch (ECP) can reconstruct the biomimetic regenerative microenvironment of an infarcted myocardium. Direct ink writing (DIW) and 3D printing can produce an ECP with precisely controlled microarchitectures. However, developing a printed ECP with high conductivity and flexibility for gapless attachment to conform to epicardial geometry remains a challenge. Herein, an asymmetrical DIW hydrophobic/hydrophilic membrane using heat-processed graphene oxide (GO) ink is developed. The “Masked spin coating” method is also developed that leads to a microscale GO (hydrophilic)/reduced GO (rGO, hydrophobic) physiological sensor, as well as a macroscale moisture-driven GO/rGO actuator. Depositing mussel-inspired polydopamine (PDA) coating on the one side of the DIW rGO , the ultrathin (approximately 500 nm) PDA-rGO (hydrophilic)/rGO (hydrophobic) microlattice (DrGOM) ECP is bestowed with the flexibility and moisture-responsive actuation that allows gapless attachment to the curved surface of the epicardium. Conformable DrGOM exhibits a promising therapeutic effect on rats' infarcted hearts through conductive microenvironment reconstruction and improved neovascularization.  相似文献   

16.
    
Mixed metal–semiconductor nanocrystal aerogels are fabricated, which are light‐emitting and highly porous macroscopic monoliths. Thiol‐stabilized CdTe and Au nanoparticles from aqueous synthesis act as building blocks for the hybrid material. The Au colloids undergo a surface‐modification to enhance the particle stability and achieve thiol functionalities. A photochemical treatment is applied for the gelation process which is found to be reversible by subsequent addition of thiol molecules. Via supercritical drying aerogels are formed. The variation of the initial CdTe to Au nanoparticle ratio permits a facile tuning of the content and the properties of the resulting aerogels. The obtained structures were characterized by means of optical spectroscopy, electron microscopy, elemental analysis, and nitrogen physisorption.  相似文献   

17.
    
Stem cells have demonstrated values in diabetic ulcer (DU) treatments. Challenges in this area are focused on enhancing the localized curative effects of stem cells and improving diabetic wound healing efficiently. Herein, a novel living microneedle (MN) patch is presented as a localized delivery system of bioactive platelet derived growth factor D (PDGF-D) and human adipose-derived stem cells (ADSCs) for DU wound treatment. Compared with traditional complicated stem cell carriers, the MN patch can keep stem cell viability for ADSCs encapsulation and delivery, and possesses good mechanical strengths to penetrate the local skin wounds noninvasively. It is demonstrated that the delivery ADSCs are with the abilities of angiogenesis promotion during the DU wound healing; while the additive PDGF-D can contribute significantly to the proliferation of ADSCs, strengthening the cell function of ADSCs and further facilitating the healing processes. Thus, living MN patches accelerate vascularization, tissue regeneration, and collagen deposition in a wounded diabetic mouse model, suggesting their potential application to DU wound healing and other therapeutic applications.  相似文献   

18.
    
Wounds, especially those caused by chronic diseases, are severe threats to human health. To facilitate their recovery, considerable efforts have been devoted to the generation of wound tissues and the detection of wound biomarkers. Here, an intelligent origami silk fibroin microneedle-structured dressing (i-SMD) with a smart drug release system, biochemical sensing, and physiological monitoring ability for epidermal sensing and wound healing, is presented. By utilizing temperature-responsive N-isopropylacrylamide (NIPAM) hydrogel and inverse opal (IO) photonic crystals (PCs) as a smart drug release system, controllable drug release is achieved on the i-SMD. The patterned microfluidic channels on the i-SMD and IO PCs enable the liquid to flow spontaneously in the channels, thereby achieving sensitive multiple biochemical analysis of inflammatory factors; meanwhile, microelectronic circuits integrated on the i-SMD enable sensitive motion monitoring. Notably, the performance of i-SMD in facilitating wound healing is demonstrated by treating full-thickness cutaneous wounds in a diabetic mouse model, indicating the remarkable prospects of i-SMD in wound management and other related biomedical fields.  相似文献   

19.
    
Persistent inflammation, characterized by the intense interplay of inflammatory chemokine secretion and immune cell infiltration, is a hallmark of many skin disorders including diabetic wounds and psoriasis with inadequate therapeutic interventions. Monocyte chemotactic protein-1 (MCP-1) is an inflammatory chemokine that plays a key role in recruiting and polarizing monocytes into pro-inflammatory macrophages to establish a vicious cycle that worsens the inflamed tissue microenvironment. Here, the sponge-like microneedles (HPMN) technology is described to alleviate inflammatory skin disorders. Heparin/4-arm PEG-NH2 network crosslinked onto microneedle surface spatially attracted and sequestered multiple inflammatory chemokines including MCP-1. Enrichment of MCP-1 on microneedles recruits and traps inflammatory monocytes within the porous structure of microneedles. Subsequent removal of microneedles not only depletes inflammatory chemokine, MCP-1, but also its cellular source. As a result, HPMN treatment facilitates 47.1% smaller open wound area in mice and 27.2% shorter wound length in pigs. To demonstrate the versatility of the HPMN technology, it is also shown that combining the method with standard-of-care immunosuppressants reduces 45.1% epidermis thickening and attenuated immune cell influx in a mouse psoriasis model. Overall, the HPMN technology is a novel demonstration of employing inflammatory chemokine and cell extraction to treat a broad range of inflammatory skin disorders.  相似文献   

20.
    
Microneedles are emerging as a minimally invasive drug delivery alternative to hypodermic needles. Current material systems utilized in microneedles impose constraints hindering the further development of this technology. In particular, it is difficult to preserve sensitive biochemical compounds (such as pharmaceuticals) during processing in a single microneedle system and subsequently achieve their controlled release. A possible solution involves fabricating microneedles systems from the biomaterial silk fibroin. Silk fibroin combines excellent mechanical properties, biocompatibility, biodegradability, benign processing conditions, and the ability to preserve and maintain the activity of biological compounds entrained in its material matrix. The degradation rate of silk fibroin and the diffusion rate of the entrained molecules can be controlled simply by adjusting post‐processing conditions. This combination of properties makes silk an ideal choice to improve on existing issues associated with other microneedle‐based drug delivery system. In this study, a fabrication method to produce silk biopolymer microstructures with the high aspect ratios and mechanical properties required to manufacture microneedle systems is reported. Room temperature and aqueous‐based micromolding allows for the bulk loading of these microneedles with labile drugs. The drug release rate is decreased 5.6‐fold by adjusting the post‐processing conditions of the microneedles, mainly by controlling the silk protein secondary structure. The release kinetics are quantified in an in vitro collagen hydrogel model, which allows tracking of the model drug. Antibiotic loaded silk microneedles are manufactured and used to demonstrate a 10‐fold reduction of bacterial density after their application. The processing strategies developed in this study can be expanded to other silk‐based structural formats for drug delivery and biologicals storage applications.  相似文献   

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