Polymers
·
2025
·Vol. 17
·期 5
·574
·
IF 4.9
Lin Fu,Hengxin Ren,Chaoxing Wang,Yaxin Zhao,Bohang Zou,Xiangyu Zhang
Polymer-based drug-controlled release systems offer greater efficacy and potency than conventional therapies. However, prominent drug side effects, lower circulation, and low drug loading capabilities limit their application range. In this work, the combination of Simvastatin (SIV) and Carvacrol (CAV) into PEG-PLGA microspheres (SIV-CAV-PP-MS) was achieved via an emulsification-solvent evaporation technique, resulting in microspheres characterized by high encapsulation efficiency and reduced particle size. In vitro studies demonstrated that the cumulative drug release increased with higher SIV and CAV levels in the release medium, reaching 88.91% and 89.35% at 25 days. Pharmacokinetic analysis revealed that the concentrations of SIV and CAV reached their maximum levels at approximately seven days in the SIV-CAV-PP-MS group, which indicates that using PEG-PLGA as a carrier significantly delays drug release. In vivo, evaluation demonstrated that the SIV-CAV-PP-MS high-dose group and positive drug control group showed reductions in low-density lipoprotein cholesterol levels by 0.39-fold and 0.36-fold compared to the Hyperlipidemia model group, and the addition of CAV significantly enhanced the lipid-lowering effects of SIV. Histological examinations indicated that the SIV-CAV-PP-MS medium-dose group displayed histological features more closely resembling those of normal mice compared to the Simvastatin control group, with a well-organized hepatocyte structure, a significant reduction in lipids, and improved liver health. The prepared polymeric microsphere utilizing SIV and SAV will be a promising dosage form for hyperlipidemia disease patients, with superior lipid-lowering efficacy and improved patient compliance.
研究领域:
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2013
·Vol. 9
·期 11
·1921-1928
·
IF 5.256
Jiang Liming,Sun Haizhu,Yuan Anliang,Zhang Kai,Li Daowei,Li Chen,Shi Ce,Li Xiangwei,Gao Kai,Zheng Changyu,Yang Bai,Sun Hongchen
Simvastatin is considered as a stimulator for bone formation. However, the half-life for simvastatin is generally 2 hours, which means, it is difficult to maintain biologically active simvastatin in vivo. To overcome this limitation, we created a system to slowly release simvastatin
in vitro and in vivo. We constructed a poly(lactic-co-glycolic acid)/hydroxyapatite nanofibrous scaffold to carry simvastatin. Releasing assays showed that simvastatin was released from poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin quickly within ∼15
days, and small amounts continued to be released through day 56 (experiments terminated). MTT assays demonstrated that both poly(lactic-co-glycolic acid)/hydroxyapatite and poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin promoted MC3T3-E1 cell proliferation. However,
Alkaline phosphatase assays showed that only poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold significantly promoted the osteogenic differentiation of MC3T3-E1 cells in vitro on day 14. To further test in vivo, we created calvaria bone defect models and
implanted either poly(lactic-co-glycolic acid)/hydroxyapatite or poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin. After 4 or 8 weeks post-implantation, the results indicated that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold induced bone formation
more efficiently than poly(lactic-co-glycolic acid)/hydroxyapatite alone. Our data demonstrates that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin has the potential to aid in healing bone defects and promoting bone regeneration in the future although we still need
to optimize this complex to efficiently promote bone regeneration.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Xuejing Yang,Wenyu Cao,Xun Gu,Lijie Zheng,Qiuyue Wang,Yingying Li,Fang Wei,Tao Ma,Lu Zhang,Qingqing Wang
Currently, one of the main problems encountered in wound healing therapy is related to inefficient drug delivery. However, dissolving microneedles (DMNs) can be administered percutaneously to effectively deliver a drug to a deep wound area. Simvastatin (SIM) can promote wound healing, albeit its insolubility in water limits its application. Here, we designed a DMNs (SIM-NC@DMNs) drug delivery system loaded with SIM nanocrystals (SIM-NC) and evaluated its efficacy in wound healing. Based on our observations, the dissolution performance of insoluble SIM is significantly improved after the preparation of SIM-NC. For example, the saturation solubility of SIM-NC in deionized water and PBS increased by 150.57 times and 320.14 times, respectively. After the SIM-NC@DMNs are deeply inserted into the wound, the needle portion, which is composed of hyaluronic acid (HA), dissolves rapidly, and the SIM-NC loaded on the needle portion is efficiently released into the deep wound area for optimal therapeutic efficacy. The combination of NC and DMNs makes this system further effective for wound healing. Our cumulative work suggests that the newly developed SIM-NC@DMNs possess great potential in accelerating wound healing. By day 12 after treatment, the residual wound area in the Control group was 21.34 %, while the residual wound area in the SIM-NC@DMNs group was only 2.36 %. This result as well as provides certain evidence of its efficacy for wound healing therapy. The SIM-NC@DMNs drug delivery system may become an efficient treatment modality that promotes wound healing, with a promising potential in the field of wound healing research.
研究领域:
药剂学
·
生物医学工程
·
伤口护理
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Li-Jun Deng,Yan-Lin Wu,Xian-Hua He,Ke-Nan Xie,Lu Xie,Yi Deng
A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2018
·
IF 5.738
Shifeng Yan,Jie Ren,Yuhang Jian,Weidong Wang,Wentao Yun,Jingbo Yin
Injectable hydrogels have shown great potential in bone tissue engineering. Simvastatin (SIM), a common hypolipidemic drug, has been suggested as a potential agent to promote bone regeneration. However, due to its hydrophobic nature, the compatibility between SIM and hydrogels is rather poor, thereby greatly affecting the drug release behavior, the mechanical properties, and dimensional stability of the hydrogels. Herein, we presented a novel design to entrap SIM in an injectable maltodextrin-based micelle/hydrogel composite system. Maltodextrin-based micelles were prepared to solubilize and encapsulate SIM. The SIM-loaded aldehyde-modified micelles were anchored to the hydrogel network and served as a cross-linker to realize improved mechanical strength of hydrogel, controlled release, and osteogenic capability of SIM. In all, this study demonstrated a strategy to incorporate drug loaded carriers into hydrogels for drug delivery and tissue engineering applications.
研究领域:
生物材料
·
药物递送
·
骨组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2018
·Vol. 73
·期 8
·465-468
·
IF 1.016
Ma Wenxue,Yao Yawen,Gu Yuyan,Li Fang,Cai Jiaxuan,He Baozhu,Chen Qiuyan,Fang Jian,Ouyang Zizhang
Acute phase protein pentraxin 3 (PTX3) is increased in patients with atherosclerotic cardiovascular diseases, such as acute coronary syndrome and coronary artery vulnerability, thereby serving as an important biomarker for the prognosis of cardiovascular diseases. This study was designed
to evaluate the effects of statins on the expression of PTX3 in human endothelial cells. We observed that PTX3 is a TNFα inducible protein in human endothelial cells. In contrast, treatment with simvastatin reduces basal as well as TNFα induced gene and protein expression of PTX3
in a dose- and time-dependent manner. Our study suggests that reducing PTX3 expression by statins could contribute to its protective effects against endothelial dysfunction and coronary artery plaque destabilization.
研究领域:
心血管疾病
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Tao Wu,Jing Sun,Lei Tan,Qi Yan,Lei Li,Liangwen Chen,Xiangmei Liu,Shi Bin
Postmenopausal osteoporosis is a common chronic dynamic bone disorder, caused by estrogen deficiency. To address this issue, we constructed a controlled drug-release system composed of poly (N-isopropylacrylamide) brush modified mesoporous hydroxyapatite (MHA-SIM-P) loaded with simvastatin (SIM) using an ovariectomised (OVX) rat model. Quantitative alkaline phosphatase activity assay, alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro . The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells (BMSCs) in vitro . In osteoporotic animal model, the therapeutic efficiency for bone defect was evaluated by μCT analysis, tartrate-resistant acid phosphatase, haematoxylin and eosin staining, which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks. This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis. Thus, this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects.
研究领域:
药理学
·
生物医学工程
·
骨科
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
·
2020
·
IF 1.466
Chongxia Huang,Du Liang,Chongbo Huang,Baolin Li,Jiandong He,Ximou Huang
Cadmium (Cd) has a direct toxic effect on bones. Statins such as simvastatin have protective effects on various diseases, including on tissue injury. The current study revealed the efficacy of simvastatin on Cd-induced preosteoblast injury. Preosteoblast MC3T3-E1 cells were incubated with various doses of CdCl2 for 12 h, 24 h and 48 h, and then the cell cytotoxicity was assessed using MTT assay and flow cytometry, respectively. The expression level of Nox4 was assessed by Western blot and qRT-PCR. The morphological appearance of MC3T3-E1 cells was observed under a microscope. Cells exposed to CdCl2 (5 µM) were further treated by simvastatin at various doses, subsequently cell viability, apoptosis and the expression of Nox4 were measured. Furthermore, to confirm the protective effects of simvastatin on Cd-induced pre-osteoblast injury, functional rescue assays were performed after corresponding cell treatment by simvastatin (10−8 M), CdCl2 (5 µM), and overexpression of Nox4. Expressions of cell apoptosis-related markers were measured by Western blot and qRT-PCR. The results revealed that CdCl2 caused MC3T3-E1 cell injury because the cell viability was decreased and the apoptosis was increased. Nox4 expression was up-regulated with the increase of CdCl2 concentrations. Simvastatin increased the cell viability, relieved the cell apoptosis and Nox4 expression previously increased by CdCl2. The effects of CdCl2 on MC3T3-E1 cells and Nox4 expression could be attenuated by simvastatin, and promoted by Nox4 overexpression. The current study found that simvastatin protects Cd-induced preosteoblast injury via Nox4, thus, it can be used as a potential drug for treating cadmium-induced bone injury.
研究领域:
药理学
·
毒理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 18
·11024-11029
·
IF 4.486
Huan Li,Anjara Rabearivony,Wenxiang Zhang,Siyu Chen,Xiaofei An,Chang Liu
The chronopharmacology refers to the utilization of physiological circadian rhythms to optimize the administration time of drugs, thus increasing their efficacy and safety, or reducing adverse effects. Simvastatin is one of the most widely prescribed drugs for the treatment of hypercholesterolaemia, hyperlipidemia and coronary artery disease. There are conflicting statements regarding the timing of simvastatin administration, and convincing experimental evidence remains unavailable. Thus, we aimed to examine whether different administration times would influence the efficacy of simvastatin. High-fat diet-fed mice were treated with simvastatin at zeitgeber time 1 (ZT1) or ZT13, respectively, for nine weeks. Simvastatin showed robust anti-hypercholesterolaemia and anti-hyperlipidemia effects on these obese mice, regardless of administration time. However, simvastatin administrated at ZT13, compared to ZT1, was more functional for decreasing serum levels of total cholesterol, triglycerides, non-esterified free fatty acids and LDL cholesterol, as well as improving liver pathological characteristics. In terms of possible mechanisms, we found that simvastatin did not alter the expression of hepatic circadian clock gene in vivo, although it failed to change the period, phase and amplitude of oscillation patterns in Per2::Luc U2OS and Bmal1::Luc U2OS cells in vitro. In contrast, simvastatin regulated the expression of Hmgcr, Mdr1 and Slco2b1 in a circadian manner, which potentially contributed to the chronopharmacological function of the drug. Taken together, we provide solid evidence to suggest that different administration times affect the lipid-lowering effects of simvastatin.
研究领域:
药理学
·
时间生物学
·
代谢性疾病
·
脂质代谢
·
心血管医学
✓ 已验证
DOI
高影响因子
Oncotarget
·
2017
·
IF 5.168
Zhen-Huan Lv,Trinh Anh Phuong,Shi-Jie Jin,Xiao-Xue Li,Ming Xu
Recent studies have demonstrated that NLRP3 inflammasome complex acts as pivotal elements to initiate inflammatory responses and plays an important role in the dysfunction of cardiovascular complications. Meanwhile, simvastatin prevents vascular endothelial dysfunction from inflammasome invasion contributing to reduce cardiovascular risk. However, Whether or not the simvastatin improves vascular endothelial barrier function through inhibiting the activation of NLRP3 inflammasome pathway remains unknown. Here, we explored the role and mechanisms of simvastatin in the activation of NLRP3 inflammasome which are involved in vascular endothelial hyperpermeability causing by the disruption of tight junction protein ZO-1 and adherens junction protein VE-Cadherin, an early initiation of cardiovascular complication. Our results found that high glucose significantly induced the formation and activation of NLRP3 inflammasome through NADPH oxidase-dependent reactive oxygen species (ROS) formation, associated with vascular endothelial hyperpermeability causing by ZO-1 and VE-Cadherin disruption in the rat aortic endothelial cells (RAECs). Simvastatin treatment remarkably abolished vascular endothelial hyperpermeability and enhanced the protein expression of ZO-1 and VE-Cadherin through NLRP3 inflammasome. Mechanistically, the inhibitory role of simvastatin endothelial hyperpermeability is attributed to the decreased release of cytoplasmic high mobility group box protein-1 (HMGB1) derived from endothelial NLRP3 inflammasome activation. We further confirm the protective role of simvastatin on vascular leakage in the heart of diabetic rats injected with Evans blue dye, which was associated with HMGB1 release in the serum. Collectively, the mechanism of simvastatin treatment alleviating vascular endothelial permeability dysfunction may be through inhibiting the NLRP3 inflammasome-dependent HMGB1 release in RAECs.
研究领域:
心血管疾病
·
药理学
·
分子生物学
·
糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANO
·
2025
·
IF 1.1
Ye Feng,Lei Zhang,Shen Chen,Baoe Li,Xiaoyan Zhao,Chunyong Liang,Hongshui Wang,Donghui Wang
Titanium (Ti) is one of the most widely used implant materials; however, postoperative failures still frequently occur due to its poor osseointegration and limited antibacterial performance. The key to accelerating bone healing and improving implantation success lies in modulating immune responses through the regulation of immune cell behaviors. In this work, simvastatin, which is reported to have the immune regulation function was loaded into photothermal TiO 2 nanotubes (diameter 60–65 nm) formed on the Ti surface and subsequently covered with an intelligent thermosensitive chitosan hydrogel (phase transition temperature 38.95 °C) to construct a light-controlled drug release system (SCTH@rNT). The release of simvastatin from TiO 2 nanotubes was precisely regulated under near-infrared (NIR) irradiation. In vitro, the SCTH@rNT + NIR system exhibited remarkable antibacterial activity, reducing the viable colonies of S . aureus and E. coli by 98.6% and 97.4%, respectively, and significantly promoting osteogenic differentiation, with alkaline phosphatase (ALP) activity 1.8-fold higher than that of the control on day 14. The controlled release further enabled immunomodulation by upregulating Interleukin-10 (IL-10) expression 2.3-fold and down-regulating Tumor Necrosis Factor-alpha (TNF-α) by 48%, thereby alleviating inflammation. In vivo, the system reduced inflammatory cell infiltration by 62.7% and markedly enhanced new bone formation. Overall, this light-controlled drug delivery platform effectively creates a favorable immune microenvironment by dynamically regulating the macrophages behaviors, showing great potential for clinical translation in improving the integration and longevity of Ti-based implants.
研究领域:
生物医学工程
·
生物材料
·
组织工程
·
药物递送
·
免疫调节
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Mengjuan Sun,Jun Wei,Yanhui Su,Yangjingwan He,Liang Ge,Yan Shen,Bohui Xu,Yanlong Bi,Chunli Zheng
Purpose The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects.Methods Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs).Results The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug’s circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug’s efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions.Conclusion RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM’s poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.
研究领域:
医学
·
药学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
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