Frontiers in Pharmacology
·
2022
·
IF 5.988
Xi Chen,Di Wang,Xuejun Guo,Xiaoming Li,Wenjing Ye,Yang Qi,Wen Gu
The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin's effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.
研究领域:
药理学
·
纳米技术
·
呼吸医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Yunhai Wei,Wenjing Hu,Huancen Guo,Jinyu Zhang,Jingrui Cao,Chu Shen,Zhongxin Wu,Lei Yin,Yuhai Gao
Immune checkpoint inhibitors (ICIs) show effectiveness in gastric cancer (GC) treatment, yet enhancing their efficacy remains challenging. We encapsulated the anticancer compound Heterophyllin B (HB) in mPEG–PLGA-NH2 nanoparticles (NPs), modified with αPDL1, forming mPEG–PLGA-NH2@HB-αPDL1 NPs. These NPs displayed low toxicity to GES-1 cells and good blood compatibility. They effectively inhibited GC cell malignant phenotypes and downregulated PD-L1 expression via the PI3K/AKT pathway. In GC allograft mice, the HB and αPDL1 combination therapy outperformed monotherapy, with the NPs showing better efficacy than free drugs. Additionally, the NPs improved the tumor immune microenvironment. H&E staining confirmed no significant toxicity to major mouse organs. Thus, mPEG–PLGA-NH2@HB-αPDL1 offers a promising strategy for optimizing ICI therapy in GC treatment.
研究领域:
纳米医学
·
肿瘤学
·
免疫治疗
·
药物递送系统
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Yanhai Xi,Weiheng Wang,Liang Ma,Ning Xu,Changgui Shi,Guohua Xu,Hailong He,Wenming Pan
Astragaloside (AS) has an anti-osteoporotic effect, but its poor water solubility and low bioavailability limit its application. In this study, a novel nano-carrier with bone targeting was prepared by modifying mPEG-PLGA with alendronate (AL) before incorporation into astragaloside nano-micelles (AS-AL-mPEG-PLGA) to enhance the oral bioavailability, bone targeting and anti-osteoporosis effect of AS. The release behavior of AS-AL-mPEG-PLGA in vitro was investigated via dialysis. The pharmacokinetics of AS-AL-mPEG-PLGA was studied in Sprague-Dawley (SD) rats. The cytotoxicity of AS-AL-mPEG-PLGA in vitro (via MTT method), coupled with bone targeting ability in vitro and in vivo were evaluated. The therapeutic effects of free AS and AS-AL-mPEG-PLGA (ELISA, micro-CT, H&E staining) were compared in osteoporotic rats. AS-AL-mPEG-PLGA with smaller particle size (45.3 ± 3.8 nm) and high absolute zeta potential (−23.02 ± 0.51 mV) were successfully prepared, wherein it demonstrated higher entrapment efficiency (96.16 ± 0.18%), a significant sustained-release effect for 96 h and acceptable safety within 10–200 μg/mL. AS-AL-mPEG-PLGA could enhance the hydroxyapatite affinity and bone tissue concentration of AS. The relative bioavailability of AS-AL-mPEG-PLGA was 233.90% compared with free AS. In addition, the effect of AS in reducing serum levels of bone metabolism-related indicators, restoring the bone microarchitecture and improving bone injury could be enhanced by AS-AL-mPEG-PLGA. AS-AL-mPEG-PLGA with small particle size, good stability, remarkable sustained-release effect, safety and bone targeting was successfully constructed in this experiment to potentially improve the oral bioavailability and anti-osteoporosis effect of AS. Thus, AS-AL-mPEG-PLGA may be a promising strategy to prevent and treat osteoporosis.
研究领域:
药剂学
·
药理学
·
纳米技术
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 4
·1-10
·
IF 4.026
Liu Xia,Zhang Mengying,Tian Yuxin,Liu Ruijia,Wang Yunfei,Guo Feifei,Gong Yanling,Yan Meixing
Luteolin (Lu) is a kind of flavonoid that has been proved to treat non-alcoholic fatty liver disease by alleviating intestinal microbiota disorder. In this study, luteolin was coated with methoxy poly(ethylene glycol)–poly(dl-lactide-co-glycolic acid) (mPEG-PLGA) using an emulsion solvent evaporation method, and the optimum preparation process was determined by a single-factor experiment combined with response surface methodology (RSM). Methacrylic acid-methyl methacrylate (1:2) copolymer (Eudragit S100) was then used to coat the surface of Lu/mPEG-PLGA nanoparticles. The physical parameters of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles (Lu-NPs), such as appearance, particle size, potential, particle size distribution and drug release, and stability in vitro, were evaluated. In addition, its cytotoxicity in vitro , pharmacokinetics, tissue distribution, and toxicity in vivo were also studied. The results showed that the prepared Lu-NPs had uniform particle size distribution, high encapsulation efficiency, and good stability. Normal colonic epithelial cells showed good tolerance to Lu-NPs. After oral administration, the blood concentration of luteolin peaked at 8 h, and the main tissue distribution was within the colon, confirming its colon-targeted profile. Safety assessments also indicated that no significant changes were observed in main organs after administration of Lu-NPs. The use of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles is a new strategy for colon-targeted delivery of luteolin that encourages luteolin to fulfill its role in the colon. Graphical abstract
研究领域:
药学
·
纳米技术
·
药物递送系统
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qin Chen,Fen-Sheng Qiu,Wei Xie,Wen-Ying Yu,Zhao-An Su,Guang-Ming Qin,You-Kun Kang,Song-Lin Jiang,Chen-Huan Yu
Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum , and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. This encapsulation efficiency was 84.4 ± 6.9 %, and the drug load was 4.02 %±0.35 %. The results showed that GPA-NP displayed more prolonged GPA release and higher bioavailability in vitro than GPA. GPA-NP obviously reduced the levels of oxidative stress markers and inflammatory cytokines in both retinal tissues of DR mice and high glucose-exposed HRMEC better than GPA alone. Mechanismly, GPA blocked the Nrf2-Keap1 interaction by binding with Kelch domain of Keap1 via alkyl and hydrogen bonds. Therefore, GPA-NP exerted more potent protectivity effects against high glucose-induced retinal microvascular endothelial ferroptosis in vitro and in vivo by activating Nrf2/HO-1/GPX4 pathway. It could be a promising therapeutic agent for preventing DR.
研究领域:
药理学
·
纳米技术
·
糖尿病
·
眼科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2015
·Vol. 27
·期 2
·1-13
·
IF 2.587
Guan Qingxia,Sun Shuang,Li Xiuyan,Lv Shaowa,Xu Ting,Sun Jialin,Feng Wenjing,Zhang Liang,Li Yongji
This study investigated the therapeutic efficiency of monomethoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA) co-loaded with syringopicroside and hydroxytyrosol as a drug with effective targeting and loading capacity as well as persistent circulation in vivo. The nanoparticles were prepared using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with syringopicroside and hydroxytyrosol (SH-NPs). The parameters like in vivo pharmacokinetics, biodistribution in vivo, fluorescence in vivo endomicroscopy, and cellular uptake of SH-NPs were investigated. Results showed that the total encapsulation efficiency was 32.38 ± 2.76 %. Total drug loading was 12.01 ± 0.42 %, particle size was 91.70 ± 2.11 nm, polydispersity index was 0.22 ± 0.01, and zeta potential was −24.5 ± 1.16 mV for the optimized SH-NPs. The nanoparticle morphology was characterized using transmission electron microscopy, which indicated that the particles of SH-NPs were in uniformity within the nanosize range and of spherical core shell morphology. Drug release followed Higuchi kinetics. Compared with syringopicroside and hydroxytyrosol mixture (SH), SH-NPs produced drug concentrations that persisted for a significantly longer time in plasma following second-order kinetics. The nanoparticles moved gradually into the cell, thereby increasing the quantity. ALT, AST, and MDA levels were significantly lower on exposure to SH-NPs than in controls. SH-NPs could inhibit the proliferation of HepG2.2.15 cells and could be taken up by HepG2.2.15 cells. The results confirmed that syringopicroside and hydroxytyrosol can be loaded simultaneously into mPEG-PLGA nanoparticles. Using mPEG-PLGA as nano-carrier, sustained release, high distribution in the liver, and protective effects against hepatic injury were observed in comparison to SH.
研究领域:
药剂学
·
药理学
·
纳米技术
·
药物递送系统
·
肝病学
✓ 已验证
DOI
PubMed
高影响因子
Nanomaterials
·
2025
·Vol. 15
·期 8
·615
·
IF 4.3
Ren Li,Yi Zhu
Sulforaphane (SFN) is a natural isothiocyanate compound with multiple bioactive effects, abundantly found in cruciferous vegetables. SFN and cadmium (Cd) were limited in their application as chemotherapeutic agents due to insufficient cellular uptake, low bioavailability, and high systemic toxicity, respectively. In this study, mPEG-PLGA nanoparticles were used as a carrier to load Cd-γ-PGA conjugates and SFN, enabling favorable drug release under acidic microenvironments with excellent pH responsiveness. The NP-Cd-SFN nanoparticles exhibited a particle size of 102.1 nm, a zeta potential of -14.48 mV, and a PDI value of 0.257. These characteristics contribute to the nanoparticles’ prolonged circulation in the bloodstream and their ability to passively target tumors. Compared to the single-dose groups and the combined Cd + SFN group, the NP-Cd-SFN group significantly reduced the viability of HepG2 cells and increased their apoptosis rate by inducing mitochondrial oxidative stress and promoting cell apoptosis. Overall, the addition of SFN and the encapsulation of mPEG-PLGA enhanced the therapeutic effects of Cd on HepG2 cells.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2019
·Vol. 55
·期 4
·1702-1714
·
IF 3.442
Shao Qi,Feng Yechen,Wang Wenwu,Wang Min,Li Binbin,El Tahchi Mario,Yin Yixia
Chemotherapeutic drugs have shown some limitations in anti-tumor treatment, such as drug resistance, high toxicity and limited regime of clinical uses. Natural products have attracted extensive attention as potential source of unmodified chemical compounds for disease treatment. Withaferin A (WA) has the potential to inhibit multiple human tumors, but it is hardly available for oral administration due to its low water solubility and its side effects. We developed a methoxy poly(ethylene glycol) (mPEG) conjugated poly( d , l -lactide- co -glycolide) (PLGA) drug carrier particles to encapsulate WA for pancreatic cancer treatment. The results showed that WA does not lose its physicochemical properties after encapsulation, and our drug carriers are completely degraded within 1 month. We used the WA-loaded mPEG–PLGA particles for pancreatic cancer cell treatment where it exhibited stronger inhibition than free drug (WA) at the early treatment stage. Our formulation of the drug carriers provides an efficient encapsulation of WA that allows it bonding with heat shock proteins, thereby reducing the expression of AKT and CDK4 proteins to induce apoptosis in cancer cells. Together, our data demonstrate that mPEG–PLGA loaded with WA can achieve the design goals for cancer therapy given its advantages of sustained release and degradation property to reduce the side effect of WA, which provides a possibility for WA to be used in clinical applications.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Qiaoyu Liu,Juanjuan Chai,Xinrui Zhang,Jingwen Xue,Lu Qin,Jian Guan,Xin Zhang,Bingjie Ma,Shirui Mao
Inhalable nanomedicines hold great promise for lung cancer therapy, yet how carrier structure dictates their pulmonary fate remains insufficiently understood. From a fundamental research perspective, this study aims to investigate how structurally distinct nanocarriers interact with physiopathological barriers in the lungs, with the goal of providing a theoretical foundation for inhalation therapy. By keeping the composition and material properties of the carriers comparable, different structured paclitaxel-loaded mPEG-PLGA nanocarriers, including nanoparticles, polymersomes, and micelles, were prepared by selecting different hydrophobic chain mPEG-PLGA diblock copolymers. It was found that nanoparticles with solid structure showed the slowest drug release rate, and the strongest cellular uptake but are difficult to overcome the barriers in the lung mucus with limited tumor permeability. In contrast, polymersomes with a less rigid structure have a better capacity to overcome the mucus and tumor barrier and therefore have the best lung retention but the weakest cellular uptake. The micelles with the smallest particle size have the strongest tumor permeability and the most prominent lymphatic distribution but the fastest drug release rate thus the most prominent extrapulmonary distribution. Remarkably, despite these divergent behaviors, their overall antitumor efficacy converged, revealing a compensatory balance among structural advantages and limitations. By bridging mechanistic insights with therapeutic outcomes, this study establishes a structure–function framework for pulmonary delivery. These findings advance fundamental understanding of how nanocarrier structure shapes drug fate and efficacy and provide generalizable principles to guide the rational design and clinical translation of inhalable nanomedicines for lung cancer and other pulmonary diseases.
研究领域:
纳米医学
·
药物递送系统
·
肺部药理学
·
癌症治疗
·
生物材料
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 10
·2350-2363
·
IF 3.641
Ji Shun-Li,Zhang Chun-Yan,Yin Xiao-Qin,Wang Jing,Wang Jia-Peng,Xu Xin
Due to low aqueous solubility and poor bioavailability of the flavone baicalein (BIC), a nano-micelle of delivery system was developed. Preparation of BIC-loaded crown ether-mPEG-PLGA micelle (BCPP-M) was performed via thin-film hydration method. Characterization of micellar excipients
was accomplished with 1H NMR, while evaluation of the optimal BCPP-M formulation was appropriately carried out through zeta potential (ZP), size of particles (PS), efficiency of encapsulation (EE) and capacity of drug loading (DL). We evaluated BIC release In-Vitro and profile
of In-Vivo pharmacokinetics. Evaluation of the anti-breast cancer property of BCPP-M using MCP-7 cells cytotoxicity and mice model was performed. Particles of BCPP-M were homogenously and spherically shaped with smaller average PS, coupled with higher EE and DL, good stability and polydispersity
index (PDI). The accumulative release of BCPP-M was obviously higher than free-BIC. Significantly, oral biological availability of BCPP-M was improved comparable to free BIC. Besides, half maximum inhibitory concentration (IC50) of BCPP-M in MCP-7 cells was lower than free-BIC. Animal experiments
also showed targeting, long circulation and antitumor potential of BCPP-M. Successful incorporation of BIC into long-acting and targeting micellar system could have enhanced solubility in aqueous media, oral In-Vivo availability and antitumor property of BIC.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物药剂学
·
药理学
✓ 已验证
DOI
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Naiyu Wang,Shiqi Kang,Qi Zeng,Wu Xu,Yuanyuan Zhao,Xudong Shi,Ruijun Li
Limited ability of nerve regeneration and the formation of nerve adhesions result to poor outcomes of peripheral nerve injury (PNI) following surgical nerve repair. Currently, there is no efficient therapy for the improvement of functional recovery after surgical repair. Rapamycin (Rapa) has been found useful for promoting nerve regeneration through removing cellular debris at the early stages after PNI. However, its lower oral bioavailability and significant adverse effects limit its clinical application. In this study, we developed a biocompatible nerve wrap based on biocompatible monomethoxy poly (ethylene gly co l)-poly (lactic- co -glycolic acid) (mPEG-PLGA) for the local delivery of Rapa. The Rapa-mPEG-PLGA nerve wrap exhibited a rough surface and good hydrophilicity with strong mechanical strength. In vitro release studies revealed an initial rapid phase within the first 8 days, followed by a stable release about 10 days. The released Rapa remained its bioactivity to induce autophagy and promote cell migration. In a rat model of sciatic nerve transection and immediate repair, the implantation of Rapa-mPEG-PLGA nerve wrap significantly enhanced axonal regeneration and myelination. Furthermore, the nerve wraps effectively prevented the occurrence of nerve adhesions. Improved functional recovery was observed with Rapa-mPEG-PLGA membrane wrap post-surgery 4 weeks and 8 weeks. In summary, the Rapa-loaded mPEG-PLGA nerve wrap promoted nerve regeneration by releasing Rapa at the early stage after injury, and acted as a physical barrier to reduce nerve adhesions. This local dual-action strategy is a promising candidate for clinical translation in the treatment of PNI following surgical repair.
研究领域:
生物医学工程
·
神经科学
·
药理学
·
生物材料
·
再生医学
✓ 已验证
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）