International Journal of Nanomedicine
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2024
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IF 6.6
Bo Wang,Jiquan Shen,Changjian Zhou,Xinggao Wang,Shuanghu Wang,Ruixing Hou
Background Rheumatoid Arthritis (RA) involves prolonged inflammation of the synovium, damaging joints and causing stiffness and deformity. Celastrol (Cel), derived from the Chinese herbal medicine Tripterygium wilfordii Hook F, offers immunosuppressive effects for RA treatment but is limited by poor solubility and bioavailability.Purpose In this study, long-circulating Cel-loaded liposomes (Cel-LPs) were used to increase the pharmacokinetics of Cel, thereby improving drug delivery and efficacy for the treatment of RA.Methods Cel-LPs were prepared and administered orally and intravenously to compare the elimination half-life of drugs and bioavailability of Cel. Cel-LPs were prepared using the lipid thin-layer-hydration-extrusion method. Human rheumatoid arthritis synovial (MH7A) cells were used to investigate the compatibility of Cel-LPs. The pharmacokinetic studies were performed on male Sprague-Dawley (SD) rats.Results The Cel-LPs had an average size of 72.20 ± 27.99 nm, a PDI of 0.267, a zeta potential of −31.60 ± 6.81 mV, 78.77 ± 5.69% drug entrapment efficiency and sustained release (5.83 ± 0.42% drug loading). The cytotoxicity test showed that liposomes had excellent biocompatibility and the fluorescence microscope diagram indicated that liposome entrapment increased intracellular accumulation of Rhodamine B by MH7A cells. Furthermore, the results exhibited that Cel-LPs improved the pharmacokinetics of Cel by increasing the elimination half-life (t1/2) to 11.71 hr, mean residence time (MRT(0-∞)) to 7.98 hr and apparent volume of distribution (Vz/F) to 44.63 L/kg in rats, compared to the Cel solution.Conclusion In this study, liposomes were demonstrated to be effective in optimizing the delivery of Cel, enabling the formulation of Cel-LPs with prolonged blood circulation and sustained release characteristics. This formulation enhanced the intravenous solubility and bioavailability of Cel, developing a foundation for its clinical application in RA and providing insights on poorly soluble drug management.
研究领域:
药剂学
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药理学
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药物递送系统
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风湿病学
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DOI
PubMed
高影响因子
Food & Function
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2022
·Vol. 13
·期 7
·4130-4141
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IF 6.317
Yao Guo,Yun-yun Shao,Yi-nan Zhao,Xiao Zhang,Zhuang-peng Chang,Yi-fan Sun,Jun-jin Liu,Jianping Gao,Rui-gang Hou
The aim of this work has been to establish and validate a simple and efficient method to detect the concentration of inulin-type fructan CPA from the roots of Codonopsis pilosula (Franch.) Nannf. in biosamples, and then apply it to evaluate the pharmacokinetics behavior, distribution character in tissue and excretion in mice. In this work, fluorescein isothiocyanate (FITC) was used to label CPA. Then FCPA was intravenously and orally administered to mice at different doses. In both i.v and p.o administration, FCPA concentration slowly declined in the circulatory system with a much longer T1/2 and MRT. After p.o administration, the area under the time curve (AUC0-∞) was dose-dependently increased. Taken together, FCPA showed poor absorption and wide tissue distribution. These pharmacokinetic results yield helpful insights into the pharmacological actions of FCPA.
研究领域:
药理学
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生物化学
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药剂学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Xinhao Song,Mengjuan Lin,Tian Fang,Jiahao Gong,Junqi Wang,Shasha Gao,Xiaolin Xu,Xin Lv,Xiuge Gao,Junren Zhang,Shanxiang Jiang,Dawei Guo
Canine mammary tumors (CMT) can severely compromise the life quality of the affected dogs through local recurrence, distant metastases and ultimately succumb to death. Recently, more attention has been given to the potential antimetastatic effect of maduramicin (MAD) on breast cancer. However, its poor aqueous solubility and toxicity to normal tissues limit its clinical application. Therefore, to address the drawbacks of MAD and enhance its anticancer and antimetastatic effects, MAD-loaded TPGS polymeric micelles (MAD-TPGS) were prepared by a thin-film hydration technique. The optimized MAD-TPGS exhibited excellent size distribution, stability and improved water solubility. Cellular uptake assays showed that TPGS polymer micelles could enhance drug internalization. Moreover, TPGS synergistically improved the cytotoxicity of MAD by targeting mitochondrial organelles, improving reactive oxygen species levels and reducing the mitochondrial transmembrane potential. More importantly, MAD-TPGS significantly impeded the metastasis of tumor cells. In vivo results further confirmed that, in addition to exhibiting excellent biocompatibility, MAD-TPGS exhibited greater antitumor efficacy than free MAD. Interestingly, MAD-TPGS displayed superior suppression of CMT metastasis via tail vein injection compared to oral administration, indicating its suitability for intravenous delivery. Overall, MAD-TPGS could be applied as a potential antimetastatic cancer agent for CMT.
研究领域:
药学
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癌症研究
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纳米技术
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兽医学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2019
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IF 7.901
Qida Hu,Wangteng Wu,Meng Wang,Shiyi Shao,Piaopiao Jin,Qi Chen,Hongzhen Bai,Xinyu Zhao,Junming Huang,Jianwei Wang,Guping Tang,Tingbo Liang
Malignancies treated by insoluble targeted agents show low dose exposure and therapeutic responses, therefore easily develop drug resistance. Nanoparticle-modified drugs might disrupt chemoresistance by increasing dose exposure and altering resistance pathways, as administrated via the intravenous route to maximize efficacy. Herein, we proposed a self-assembled nanocapsulation strategy to construct a nanocomplex with multiarm polymer and novel dendrimer series (MAP-mG3) for encapsulating insoluble inhibitors by nucleotide lock. MAP-mG3 delivering the mammalian target of rapamycin (mTOR) inhibitor OSI-027 (MAP-mG3/OSI-027) showed higher loading capacity, enhanced solubility, controlled release, and increased intracellular tumoral accumulation. MAP-mG3/OSI-027, more efficiently than the free targeted agents, attenuated mTOR phosphorylation and inhibited growth of pancreatic cancer cells. In addition, MAP-mG3/OSI-027 reverted chemoresistance to OSI-027 in drug resistance pancreatic cancer by increasing intracellular dose exposure, as well as regulating ABCB1 expression and compensatory pathways. The optimized nanocapsulation design provides an effective strategy to engineer and reactivate insoluble targeted agents for chemoresistant applications.
研究领域:
药理学
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纳米技术
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肿瘤学
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DOI
PubMed
高影响因子
Nano Today
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2024
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IF 13.2
Jinlian He,Xinyi Dai,Ziyang Wang,Jingjie Ye,Jiangbo Wang,Jun Feng,Xian-Zheng Zhang
Developing drug-free nanotherapeutics is extremely appealing provided they could achieve effective therapeutic performances. This study proposes a sodium bicarbonate-dependent gas therapy modality targeting fragile lysosomes of cancer cells through carbon dioxide-induced lysosomal rupture. Interestingly, we reveal that this gas therapy induces cell death through the combination of necrosis, pyroptosis and ferroptosis, rather than the conventional apoptosis pathway. Notably, the high water-solubility of sodium bicarbonate presents a significant challenge in engineering its nanotherapeutics that require long-term water-tolerance for its intravenous delivery. To address this issue, an EPDPPP approach is here developed under aqueous conditions. Without any anticancer drugs, the sodium bicarbonate nanoparticles alone can selectively kill cancer cells with high specificity. Thanks to the high water tolerance, the sodium bicarbonate nanoparticles coated with cancer cell membranes have shown favorable performance in targeting and inhibiting tumors after intravenous administration. This water-tolerant sodium bicarbonate nanoplatform is expected to have potential applications in various medical fields, including the targeted gas therapy. Additionally, this study may suggest a viable direction for developing water-tolerant nanoparticles derived from water-soluble inorganic salts.
研究领域:
纳米技术
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癌症治疗
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材料科学
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药学
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生物医学工程
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DOI
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Wenzhe Yang,Xue Pan,Peng Zhang,Xue Yang,Huashi Guan,Huan Dou,Qian Lu
Rationale Reversing the hypoxic and immunosuppressive tumor microenvironment (TME) is crucial for treating malignant melanoma. Seeking a robust platform for the effective reversion of hypoxic and immunosuppressive TME may be an excellent solution to revolutionizing the current landscape of malignant melanoma treatment. Here, we demonstrated a transdermal and intravenous dual-administration paradigm. A tailor-made Ato/cabo@PEG-TK-PLGA NPs were administrated transdermally to melanoma with the help of a gel spray containing a skin-penetrating material borneol. Nanoparticles encased Ato and cabo were released and thereby reversed the hypoxic and immunosuppressive tumor microenvironment (TME).Methods Ato/cabo@PEG-TK-PLGA NPs were synthesized through a self-assembly emulsion process, and the transdermal ability was assessed using Franz diffusion cell assembly. The inhibition effect on cell respiration was measured by OCR, ATP, and pO2 detection and in vivo photoacoustic (PA) imaging. The reversing of the immunosuppressive was detected through flow cytometry analysis of MDSCs and T cells. At last, the in vivo anti-tumor efficacy and histopathology, immunohistochemical analysis and safety detection were performed using tumor-bearing mice.Results The transdermally administrated Ato/cabo@PEG-TK-PLGA NPs successfully spread to the skin surface of melanoma and then entered deep inside the tumor with the help of a gel spray and a skin puncturing material borneol. Atovaquone (Ato, a mitochondrial-respiration inhibitor) and cabozantinib (cabo, a MDSCs eliminator) were concurrently released in response to the intratumorally overexpressed H2O2. The released Ato and cabo respectively reversed the hypoxic and immunosuppressive TME. The reversed hypoxic TME offered sufficient O2 for the intravenously administrated indocyanine green (ICG, an FDA-approved photosensitizer) to produce adequate amount of ROS. In contrast, the reversed immunosuppressive TME conferred amplified systemic immune responses.Conclusion Taken together, we developed a transdermal and intravenous dual-administration paradigm, which effectively reversed the hypoxic and immunosuppressive tumor microenvironment in the treatment of the malignant melanoma. We believe our study will open a new path for the effective elimination of the primary tumors and the real-time control of tumor metastasis.
研究领域:
癌症生物学
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纳米技术
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药学
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免疫疗法
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DOI
PubMed
高影响因子
Nanoscale
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2024
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IF 5.8
Penghui Wang,Yuling Wang,Xuelin Xia,Jingchun Wu,Jintang Lin,Wei Huang,Deyue Yan
Combination therapy has proven effective in counteracting tumor multidrug resistance (MDR). However, the pharmacokinetic differences among various drugs and inherent water insolubility for most small molecule agents greatly hinder their synergistic effects, which makes the delivery of drugs for combination therapy in vivo a key problem. Herein, we propose a protonated strategy to transform a water-insoluble small molecule drug-inhibitor conjugate into an amphiphilic one, which then self-assembles into nanoparticles for co-delivery in vivo to overcome tumor MDR. Specifically, paclitaxel (PTX) is first coupled with a third-generation P-glycoprotein (P-gp) inhibitor zosuquidar (Zos) through a glutathione (GSH)-responsive disulfide bond to produce a hydrophobic drug-inhibitor conjugate (PTX-ss-Zos). Subsequently treated with hydrochloric acid ethanol solution (HCl/EtOH), PTX-ss-Zos is transformed into the amphiphilic protonated precursor and then forms nanoparticles (PTX-ss-Zos@HCl NPs) in water by molecular self-assembly. PTX-ss-Zos@HCl NPs can be administered intravenously and accumulated specifically at tumor sites. Once internalized by cancer cells, PTX-ss-Zos@HCl NPs can be degraded under the overexpressed GSH to release PTX and Zos simultaneously, which synergistically reverse tumor MDR and inhibit tumor growth. This offers a promising strategy to develop small molecule self-assembled nanoagents to reverse tumor MDR in combination therapy.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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DOI
高影响因子
危险品化学品经营许可证（带存储）