PARASITOLOGY RESEARCH
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2022
·Vol. 121
·期 2
·675-689
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IF 2.383
Haseeb Muhammad,Huang Jianmei,Lakho Shakeel Ahmed,Yang Zhang,Hasan Muhammad Waqqas,Ehsan Muhammad,Aleem Muhammad Tahir,Memon Muhammad Ali,Ali Haider,Song Xiaokai,Yan Ruofeng,Xu Lixin,Li Xiangrui
Eimeria maxima (E. maxima) are an intracellular apicomplexan protozoan that causes intestinal coccidiosis in chickens. The purpose of this research was to develop a novel delivery approach for recombinant E. maxima (rEm) 14-3-3 antigen to elicit enhanced immunogenic protection using poly (D, L-lactide-co-glycolide) (PLGA) and chitosan (CS) nanoparticles (NPs) against E. maxima challenge. The morphologies of prepared antigen-loaded NPs (PLGA/CS-rEm14-3-3 NPs) were visualized by a scanning electron microscope. The rEm14-3-3 and PLGA/CS-rEm14-3-3 NPs–immunized chicken-induced changes of serum cytokines, IgY-antibody level, and T-lymphocyte subsets and protective efficacies against E. maxima challenge were evaluated. The results revealed that encapsulated rEm14-3-3 in PLGA and CS NPs presented spherical morphology with a smooth surface. The chickens immunized with only rEm14-3-3 and PLGA/CS-rEm14-3-3 NPs elicited a significant ( p <0.05) higher level of IFN-γ cytokine, stimulated the proportions of CD4 + /CD3 + , CD8 + /CD3 + T-cells, and provoked sera IgY-antibody immune response compared to control groups (PBS, pET-32a, PLGA, and CS). Whereas, PLGA-rEm14-3-3 NP–immunized chicken provoked a higher level of IFN- γ production and IgY-antibody response rather than CS-rEm14-3-3 and bare antigen, relatively. The animal experiment results ratified that PLGA-rEm14-3-3 NP–immunized chicken significantly alleviated the relative body weight gain (%), decreased lesion score, and enhanced oocyst decrease ratio compared to CS-rEm14-3-3 NPs and only rEm14-3-3. The anti-coccidial index of the chicken vaccinated with the PLGA-rEm14-3-3 NPs was (180.1) higher than that of the Cs-rEm14-3-3 NPs (167.4) and bare antigen (165.9). Collectively, our statistics approved that PLGA NPs might be an efficient antigen carrier system (Em14-3-3) to act as a nanosubunit vaccine that can improve protective efficacies in chicken against E. maxima challenge.
研究领域:
兽医学
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免疫学
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纳米技术
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DOI
PubMed
高影响因子
Antibiotics-Basel
·
2024
·Vol. 13
·期 3
·228
·
IF 4.3
Xuanxuan Ma,Na Yang,Ruoyu Mao,Ya Hao,Da Teng,Yinhua Huang,Jianhua Wang
Antimicrobial peptides (AMPs) are antibiotic candidates; however, their instability and protease susceptibility limit clinical applications. In this study, the polylactic acid–glycolic acid (PLGA)–polyvinyl alcohol (PVA) drug delivery system was screened by orthogonal design using the double emulsion–solvent evaporation method. NZ2114 nanoparticles (NZ2114-NPs) displayed favorable physicochemical properties with a particle size of 178.11 ± 5.23 nm, polydispersity index (PDI) of 0.108 ± 0.10, ζ potential of 4.78 ± 0.67 mV, actual drug-loading rate of 4.07 ± 0.37%, encapsulation rate of 81.46 ± 7.42% and cumulative release rate of 67.75% (120 h) in PBS. The results showed that PLGA encapsulation increased HaCaT cell viability by 20%, peptide retention in 50% serum by 24.12%, and trypsin tolerance by 4.24-fold. Meanwhile, in vitro antimicrobial assays showed that NZ2114-NPs had high inhibitory activity againstStaphylococcus epidermidis(S. epidermidis) (4–8 μg/mL). Colony counting and confocal laser scanning microscopy (CLSM) confirmed that NZ2114-NPs were effective in reducing the biofilm thickness and bacterial population ofS. epidermidisG4 with a 99% bactericidal rate of persister bacteria, which was significantly better than that of free NZ2114. In conclusion, the results demonstrated that PLGA nanoparticles can be used as a reliable NZ2114 delivery system for the treatment of biofilm infections caused byS. epidermidis.
研究领域:
药学
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微生物学
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材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhixin Lei,Longfukang Yao,Yuqing Tan,Zhiqun Lei,Taolei Sun
The overexpression of virulence factors and the induced inflammatory cytokine storm, resulting in tissue damage, represent significant challenges in treating antibiotic-resistant bacterial infections with conventional antibiotics. Herein, we have developed a bifunctional nanoparticle loaded with antibiotics (PSA@PLGA-TD/SMT) designed for precise response to the virulence proteins of drug-resistant bacteria while protecting the host from excessive inflammatory damage. This is achieved by modifying polylactic- co -glycolic acid (PLGA) nanoparticles with polysialic acid (PSA). Tildipirosin (TD), through hydrophobic interactions, is encapsulated within the core, while S-Methylisothiourea (SMT) is electrostatically adsorbed onto the shell layer. In vitro, the polysialic acid in the nanoparticles interacts with the neuraminidase overexpressed on the surface of Glaesserella parasuis (Gps), triggering disintegration and subsequent release of TD, which effectively kills the bacteria. Additionally, SMT functions to suppress the secretion of inducible nitric oxide synthase (NOS2), promoting the phenotypic transformation of macrophages and reducing the expression of pro-inflammatory factors. Ultimately, PSA@PLGA-TD/SMT achieves an extended drug circulation time through its prolonged retention effect, effectively alleviating discomfort caused by resistant bacteria. Therefore, the construction of nanocarriers for precise targeting of drug-resistant pathogens, delivering antibiotics, and preventing host-induced inflammatory damage presents an effective treatment strategy. This approach not only addresses the direct issue of bacterial eradication but also mitigates the collateral damage typically associated with severe infections, offering a more comprehensive and nuanced approach to managing drug-resistant bacterial infections.
研究领域:
生物医学工程
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微生物学
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药理学
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DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 19
·10623-10638
·
IF 6.895
Fabiao Hu,Ting Yan,Wei Guo,Qiuli Liu,Myong Hun Han,Chang Liu,Yuping Liu,Wenyun Zheng,Fang You,Yi Yang,Wenliang Zhang,Xingyuan Ma
Therapeutic recombinant proteins have numerous advantages and benefits over chemical drugs, particularly high specificity and good biocompatibility. However, the therapeutic potential and clinical application of current anticancer protein drugs are limited as most biomarkers are located within cells, and multiple physiological barriers exist between the point of administration and the intracellular biomarker. Herein, we report a novel strategy to accurately deliver a cell-permeable dominant-negative TATm-Survivin (TmSm) protein (T34A) to intracellular survivin in cancer cells by overcoming multiple barriers in vivo. A poly(D,L-lactide-co-glycolide) (PLGA) inner core, a polyethylene glycol (PEG) modification, and a TATm peptide were simultaneously introduced to mediate tumor tissue targeting and response to pH-triggered TmSm release. Compared to free TmSm, the PEGylated-PLGA nanoparticle platform achieved a significantly higher cellular uptake efficiency (1.79-fold for A549 and 1.77-fold for Capan-2), effectively decreased IC50 (1.22-fold for A549 and 1.17-fold for Capan-2), and largely elevated apoptosis in different cancer cells (1.17-fold for A549 and 1.15-fold for Capan-2). Besides, this newly developed nanoplatform showed increased protein drug accumulation in the tumor site in A549-bearing nude mice and reached a tumor inhibition rate of 55.81% (1.35-fold versus free TmSm) by reducing the expression of intracellular survivin. All these results confirmed that our newly developed delivery strategy is a very promising tool, which helps protein drugs to cross multiple barriers in vivo and achieves precise targeting to intracellular biomarkers. This strategy could also be applied to other types of protein drugs to further improve their clinical anticancer therapeutic efficacy.
研究领域:
肿瘤学
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药剂学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Innovative Optical Health Sciences
·
2023
·
IF 2.5
Changqiang Xie,Yan Wang,Zhenzhen Cai,Jianghai Du,Zhengyu Chen,Junjie Wang,Xingzhou Peng
Monomethyl auristatin E (MMAE) is a derivative of the marine peptide Dolastatin 10, which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials. The antibody drug conjugate (ADC) of MMAE is currently used in clinical practice. However, the safety issues of MMAE-based ADC, such as high drug toxicity and poor bioavailability, still exist when using it for anticancer therapy. A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects. Herein, PLGA-b-PEG 2 0 0 0 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy. The sustained release effect and the immunogenic cell death (ICD) effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments. The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention (EPR) effect, inducing cell apoptosis and causing a certain degree of immune response. The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC. Overall, this study provides a safe and effective chemotherapeutic approach, as well as a simple and effective synthetic process for MMAE-based nanoparticles, improving their therapeutic efficacy and safety.
研究领域:
药学
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肿瘤学
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生物材料学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
·
IF 5.2
Yuxue Pan,Danhui Hu,Honglei Chen,Mengyuan Wang,Xiaocong Dong,Guoyun Wan,Hongbo Tang,Haijiao Wang,Hongli Chen
This study focuses on the preparation and characterization of platelet membrane biomimetic nanocarriers (P-PLGA NPs) and investigates their interactions with the transplacental barrier. Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) were coated with platelet membrane (PLTM) to construct P-PLGA NPs. Additionally, fluorinated polyethylenimine (F-PEI) was grafted onto PLGA NPs to prepare F-PEI-PLGA NPs, which were compared with PLGA NPs. In vitro placental barrier cell models using human choriocarcinoma cells (BeWo b30) and in vivo pregnancy animal models using ICR mice were utilized to evaluate the transplacental barrier efficiency of the PLGA NPs with different surface modifications. The results demonstrated that all three types of nanoparticles could accumulate in the uterus and placenta. The transplacental barrier efficiency of F-PEI-PLGA NPs was found to be the highest at 4 h, while P-PLGA NPs exhibited the highest transplacental barrier efficiency at 12 and 24 h. Furthermore, there were no significant effects on the main organs, structure, and quantity of uterine spiral arteries, indicating the safety of the nanoparticles (NPs). P-PLGA NPs are expected to be a safe and effective nano-delivery system for perinatal drug delivery. This study provides insights into the transplacental barrier mechanism of NPs with different surface characteristics.
研究领域:
药学
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生物医学工程
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妇产科学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chenchen Bi,Aiping Wang,Yongchao Chu,Sha Liu,Hongjie Mu,Wanhui Liu,Zimei Wu,Kaoxiang Sun,Youxin Li
Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.
研究领域:
药剂学
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神经科学
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药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Wentao Ma,Shiwen Gong,Xianbiao He,Die Hu,Bo Cheng,Jing Yang,Binbin Li,Xinyu Wang
Thrombosis is a critical marker of cardiovascular diseases such as stroke and myocardial infarction. Timely diagnosis and dissolution of thrombi can significantly reduce patient mortality risk. Theranostic nanoparticles with targeting capabilities offer a promising solution to this issue. We developed fucoidan-modified PLGA nanoparticles loaded with indocyanine green (ICG) and lumbrokinase (LK) (FCP-ICG@LK NPs) to achieve integrated diagnosis and treatment of thrombotic diseases while minimizing hemorrhagic risks. Targeting experiments demonstrated the affinity of fucoidan for P-selectin. In a mouse model of carotid thrombosis, FCP-ICG@LK NPs demonstrated excellent diagnostic and monitoring capabilities while effectively dissolving thrombi under near-infrared light. Compared with free LK, FCP-ICG@LK NPs showed better thrombolysis effects at the same dose. Furthermore, bleeding risk assessment experiments indicated that FCP-ICG@LK NPs do not induce hemorrhagic risks. FCP-ICG@LK NPs showed no significant cytotoxicity or hemolysis. These results indicate that fucoidan-modified PLGA drug-loaded nanoparticles are a promising thrombus-targeted theranostic agent.
研究领域:
生物医学工程
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药剂学
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心血管疾病研究
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DOI
高影响因子
Soft Matter
·
2020
·Vol. 16
·期 46
·10528-10536
·
IF 3.14
Can Wu,Chunlu Wang,Lu Sun,Keming Xu,Wenying Zhong
Localized drug delivery offers great therapeutic efficacy at local tissues while avoiding the systemic toxicity of drugs. Yet it demands the development of structurally-stable drug carrier systems with excellent injectability, as well as the capability to facilitate controlled release of multiple drugs. Herein, we describe the design and synthesis of a supramolecular hydrogel (Cis/Peptide@NP/Irino) for the combined delivery of cisplatin (Cis) and irinotecan (Irino). The self-assembled hydrogel consisted of an inner phase of irinotecan-loaded PLGA nanoparticles (NP/Irino) and an outer phase of cisplatin-loaded peptide nanofibers (Cis/Peptide). Through the structural reinforcement of PLGA nanoparticles, the Cis/Peptide@NP/Irino hydrogel exhibited better mechanical properties than Cis/Peptide or Peptide hydrogels. With excellent shear-thinning properties, it facilitated the development of a localized drug delivery system with an improved retention time in vivo. The hydrogel incorporated two anticancer drugs, Cis and Irino, at the Peptide and PLGA domains, respectively, and exhibited a faster release of Cis prior to the continuous release of Irino in vitro. Furthermore, the Cis/Peptide@NP/Irino formulation showed a better inhibition efficacy against the proliferation of cancerous A549 cells, with the synergism of Cis and Irino exceeding that of the simple solution mixtures, which was plausibly due to the enhanced cellular uptake of drugs through endocytosis. We believe that structurally-stable supramolecular hydrogels show great promise in the local delivery of various drug combinations for cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
ADVANCES IN POLYMER TECHNOLOGY
·
2020
·
IF 1.539
Lei Li,Yan Li,Cheng Miao,Rui Liu
This study was to explore the therapeutic effect and mechanism of puerarin (PUE) combined with PEGylated nanoparticles on a rat cerebral infarction cell model. In this context, PEG-PLGA/PUE nanoparticles were prepared by the thin-film hydration method, and the toxicity of PEG-PLGA/PUE nanoparticles to brain capillary endothelial cell (BCEC) was detected by MTT. The BCEC/TF cell model was obtained by induction of BCEC cells with TNF-α. The BCEC/TF cell model was identified by immunofluorescence; the protein expression was detected by western blotting; the expression level of miR-424 in cells was measured by RT-qPCR; the targeting relationship between miR-424 and PDCD4 was confirmed by dual-luciferase reporter assay. We found that PEG-PLGA/PUE nanoparticles prepared by the thin-film hydration method had uniform particle size, regular shape, and good stability and were not toxic to cells. The vWF was widely expressed in the cytoplasm in BCECs. The BCEC/TF cell model was obtained after TNF-α treatment, and tissue factor (TF) was widely expressed on the cell membrane of BCEC/TF cells. Furthermore, it was observed that the PEG-PLGA/PUE nanoparticles showed better therapeutic effect on the BCEC/TF cell model than PUE. PEG-PLGA/PUE nanoparticles and PUE inhibited the expression of PDCD4 protein by increasing the expression of miR-424 in BCEC/TF cells. In summary, the therapeutic effect of PEG-PLGA/PUE nanoparticles on the in vitro cell model of cerebral infarction is better than that of PUE. Moreover, PEG-PLGA/PUE inhibits the expression of PDCD4 protein by lowering the expression level of miR-424 in cells, thereby reducing the hazard of cerebral infarction.
研究领域:
药理学
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神经科学
·
分子生物学
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2025
·
IF 6.5
Qingyue Da,Min Xu,Yiting Tian,Huiping Ma,Haibo Wang,Linlin Jing
Background: Oxidative stress is considered an important mechanism of acute high-altitude brain injury. Imidazole nitronyl nitroxide radicals are a class of stable organic radical scavengers that contain single electrons in their molecules. Therefore, in order to search for compounds with low toxicity and better effect against high-altitude brain injury, the preparation methods of PLGA nanoparticles (TPP-C6-HPN@PLGA-NPs) loaded with a synthesized mitochondria targeting imidazole nitronyl nitroxide were emphasized and investigated. Furthermore, its protective effect on brain injury caused by low-pressure hypoxia (HH) in mice was evaluated.Methods: Nanoparticles were prepared by emulsion solvent evaporation method, and the preparation method was optimized by Box Behnken design based on particle size, encapsulation efficiency (EE) and drug loading (DL). Physical characterization and release studies of the optimized NPs were conducted. The high altitude brain injury mice model was selected to evaluate the therapeutic effect of TPP-C6-HPN@PLGA-NPs in vivo. The histological and biochemical tests were conducted in serum and brain of mice exposed to HH condition.Results: The nanoparticle size was 120.63 nm, the EE was 89.30%, the DL was 6.82%, the polydispersity index (PDI) was 0.172, and the zeta potential was − 22.67 mV under optimal preparation process. In addition, TPP-C6-HPN@PLGA-NPs owned good stabilities and sustained drug releases. TPP-C6-HPN@PLGA-NP exhibited lower toxicity than TPP-C6-HPN and was well uptaken by PC12 cells. Histological and biochemical analysis demonstrated that TPP-C6-HPN@PLGA-NPs significantly reduced HH induced pathological lesions, oxidative stress, energy dysfunction and inflammation response of brain tissue. Furthermore, nanoparticles did not show significant toxicity to major organs such as the liver and kidneys, as well as hematology in mice.Conclusion: TPP-C6-HPN@PLGA-NPs exhibits good stability, low hemolysis rate, sustained release, low toxicity, and long residence time in brain tissue and can be used as a promising formulation for the proper treatment of HH-induced brain damage.
研究领域:
药学
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神经科学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Baohua Li,Geng Lu,Wenbin Liu,Liqi Liao,Junfeng Ban,Zhufen Lu
Introduction The tight structure of the blood–brain barrier severely limits the level of drug therapy for central nervous system disorders. In this study, a novel composite delivery system combining nanocarrier and microneedle technology was prepared to explore the possibility of transdermal delivery of drugs to work in the brain.Methods Nanoparticle solutions containing paroxetine and rhodamine-B were prepared using PLGA as a carrier by the emulsification-solvent volatilization method. Then, they were mixed with hyaluronic acid and the PLGA nanoparticulate-based microneedle system (Rh-NPs-DMNs) was prepared by a multi-step decompression-free diffusion method. The particle size, zeta potential, and micromorphology of the nano solution were measured; the appearance, mechanical strength, dissolution properties, and puncture effect of the Rh-NPs-DMNs were evaluated; also, it was evaluated for in vivo live imaging properties and in vitro skin layer transport and distribution properties.Results The mean particle size of Rh-NPs was 96.25 ± 2.26 nm; zeta potential of 15.89 ± 1.97 mV; PDI of 0.120 ± 0.079. Rh-NPs-DMNs had a high needle content of 96.11 ± 1.27% and a tip height of 651.23 ± 1.28 μm, with excellent mechanical properties (fracture force of 299.78 ± 1.74 N). H&E skin tissue staining showed that Rh-NPs-DMNs produced micron-sized mechanical pores approximately 550 μm deep immediately after drug administration, allowing for efficient circulation of the drug; and the results of in vivo imaging showed that Rh-B NPs DMNs had a faster transport rate than Rh-B DMNs, with strong fluorescent signals in both brain (P<0.01) and hippocampus (P<0.05) 48 h after drug administration.Conclusion Nanoparticles can prolong blood circulation time and intracerebral retention time and have certain brain-targeting properties due to their excellent physical properties. The use of microneedle technology combined with nanocarriers provides new ideas for delivery systems for the treatment of central neurological diseases.
研究领域:
药剂学
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神经科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）