CRYSTENGCOMM
·
2021
·Vol. 23
·期 27
·4871-4878
·
IF 3.545
Guojia Yu,Xinjian Chen,Lichao He,Xiangrong Li,Zhiyong Zhou,Zhongqi Ren
The solubility of insoluble telmisartan (TEL) was improved by forming new cocrystal forms with several aromatic carboxylic acids. All solid forms showed three dissolution modes: TEL–HBA achieved the maximum release equilibrium within 30 min and maintained a stable and efficient dissolution level within 6 h. TEL–3-HBA and TEL–2,5-DHBA showed a slowly declining trend over time up to 6 h. TEL–3,5-DHBA conformed to the “spring and parachute” model. The TEL–HBA mixture was the most stable and was selected for further thermodynamic study, which found a 1 : 1 complexation with HCl (0.1 M) solution.
研究领域:
药学
·
材料科学
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产品关联
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2014
·
IF 2.006
Lin Zhong,Xingyi Zhu,Bo Yu,Weike Su
The amorphous solid dispersions of telmisartan salts were prepared by cogrinding, in presence of alkalizers and polyvinylpyrrolidone (PVPk30). Five alkalizers in this study were MgO, Na2CO3, K2CO3, NaHCO3 and meglumine. In soft mode using a roll mill, the drug could not form salt with MgO or NaHCO3, whereas partial drug had been transformed into salt with carbonates or meglumine. Under cogrinding, the organic base meglumine was easier to react with telmisartan than other two carbonates. For getting good dissolution performance, the drug had to be transformed into salt completely. A high intensity oscillating mill was applied for producing telmisartan meglumine salt. Multi-instrumental characterizations attested the formation of amorphous salt by high mechanical process, involving dissolution test, fourier transform infrared spectroscopy and powder X-ray diffractometry. It was evident that solid dispersions of telmisartan meglumine salt significantly increased the drug dissolution rate in intestinal fluid.
研究领域:
药剂学
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药物化学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2018
·
IF 4.513
Xie-Mei Dong,Yan-Yue Lou,Kai-Li Zhou,Jie-Hua Shi
Telmisartan (TMST) can block selectively and irreversibly an angiotensin II receptor type 1 (AT1), but has no effect on other receptor systems and also induce human prostate cancer cell apoptosis. In this work, domain specific association of TMST with calf thymus DNA was explored through multi-spectral methodologies and theoretical calculation. The results of absorption spectroscopy revealed that TMST interacting with ct-DNA formed the TMST–ct-DNA complex through non-covalent interaction and the association constant ( K a ) was of 2.71 × 10 3 M −1 at 298 K. Based on the thermodynamic analysis , it can be inferred that the interacting TMST with ct-DNA was an enthalpy-driven, spontaneous, and exothermic process due to the Δ G 0 < 0, Δ H 0 < 0, and |Δ H 0 |> T |Δ S 0 | under the studied temperature ranges. The domain interacting forces for interacting TMST with ct-DNA were van der Waals forces and hydrogen bonding interaction due to the Δ H 0 < 0 and Δ S 0 < 0. Meanwhile, the electrostatic and hydrophobic interactions also played a supporting function. Additionally, from experiments and theoretical calculation (molecular docking), it was also confirmed that TMST interacted to a minor groove of the C-G rich region of ct-DNA and resulted in the slight alteration in the secondary structure of ct-DNA whereas the obvious alteration in the geometry of TMST after binding to DNA, indicating that the flexibility of TMST contributed to stabilizing the TMST–ct-DNA complex.
研究领域:
药理学
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生物化学
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产品关联
DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2020
·
IF 2.369
Wenju Liu,Zehua Bao,Yanmin Shen,Yajun Guo
In this work, ternary phase diagrams of telmisartan-saccharin (TEL-SAC) cocrystal in methanol, ethanol, and quasi-ternary sections of the quaternary system TEL-SAC–chloroform–methanol were determined at 298.15 and 308.15 K. The results show that the stable region of cocrystal is greatly biased towards SAC in methanol and ethanol; this is due to the large solubility difference between TEL and SAC. In the mixed solvent of chloroform and methanol, the cocrystal stable region appears at the center of the whole phase diagram when the mass fraction of chloroform is 80%, which indicated that the solubility difference between TEL and SAC in the mixed solvent was relatively small. Moreover, the solubility behavior of TEL-SAC cocrystal was studied and the results showed that the solution complexation model in methanol and ethanol was 1:1 + 1:2, and the complexation model in chloroform and binary mixtures of chloroform/methanol was 1:1.
研究领域:
药学
·
物理化学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2010
·
IF 3.151
Yanzhuo Zhang,Tongying Jiang,Qiang Zhang,Siling Wang
Spherical mesocellular foam (MCF) with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. The feasibility of the prepared MCF nanoparticles for oral drug delivery was studied. A model drug, telmisartan (TEL), was loaded onto MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The drug-release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), wide-angle X-ray scattering (WXRS), differential scanning calorimetry (DSC) and HPLC demonstrated the successful incorporation of TEL into the MCF host. It is found that spherical MCF has a high drug loading efficiency up to 42.9% (drug weight/total weight) and higher than that of SBA-15 with a pore diameter of 6.5 nm. It is shown that a fast release rate of TEL was obtained from MCF compared with SBA-15 and pure crystalline TEL using enzyme-free simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement of water-insoluble drugs.
研究领域:
药剂学
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材料科学
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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
JOURNAL OF CONTROLLED RELEASE
·
2010
·
IF 5.949
Yanzhuo Zhang,Zhuangzhi Zhi,Tongying Jiang,Jinghai Zhang,Zhanyou Wang,Siling Wang
The purpose of this study was to develop mesoporous silica nanoparticles (MSNs) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MSNs were synthesized using an organic template method in an oil/water phase, and large pore diameter MSNs were functionalized with aminopropyl groups through postsynthesis. MSNs as well as the resulting functionalized MSNs were investigated as matrices for loading and release of the model drug telmisartan (TEL). The effects of different pore sizes and surface chemical groups on TEL uptake and release were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption , X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC. The total pore volume and the pore diameter of MSNs were the two main factors limiting the maximum drug load capacity. MSNs allow a very high drug loading of about 60% in weight. The release rate of TEL from MSNs with a pore diameter of 12.9 nm was found to be effectively increased and the release rate of TEL from the functionalized MSNs was effectively controlled compared with that from the unmodified MSNs. We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement and/or sustained release of poorly water-soluble drugs.
研究领域:
药剂学
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纳米医学
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Siyu Wu,Jiayi Ma,Jun Liu,Chun Liu,Su Ni,Ting Dai,Yan Wang,Yiping Weng,Hongbin Zhao,Dong Zhou,Xiubo Zhao
Biomaterial–immune system interactions play an important role in postimplantation osseointegration to retain the functionality of healthy and intact bones. Therefore, appropriate osteoimmunomodulation of implants has been considered and validated as an efficient strategy to alleviate inflammation and enhance new bone formation. Here, we fabricated a nanostructured PCL/PVP (polycaprolactone/polyvinylpyrrolidone) electrospinning scaffold for cell adhesion, tissue ingrowth, and bone defect padding. In addition, telmisartan, an angiotensin 2 receptor blocker with distinct immune bioactivity, was doped into PCL-/PVP-electrospun scaffolds at different proportions [1% (TPP-1), 5% (TPP-5), and 10% (TPP-10)] to investigate its immunomodulatory effects and osteoinductivity/conductivity. Telmisartan-loaded scaffolds displayed in vitro anti-inflammatory bioactivity on lipopolysaccharide-induced M1 macrophages by polarizing them to an M2-like phenotype and exhibited pro-osteogenic properties on bone marrow-derived mesenchymal stem cells (BMSCs). Histological analysis and micro-CT results of a rat skull defect model also showed that the telmisartan-loaded scaffolds induced a higher M2/M1 ratio, less inflammatory infiltration, and better bone regenerative patterns. Furthermore, activation of the BMP2 (bone morphogenetic protein-2)-Smad signaling pathway was found to be dominant in telmisartan-loaded scaffold-mediated macrophage–BMSC interactions. These findings indicate that telmisartan incorporation with PCL/PVP nanofibrous scaffolds is a potential therapeutic strategy for promoting bone healing by modulating M1 macrophages to a more M2 phenotype at early stages of postimplantation.
研究领域:
生物材料
·
免疫学
·
组织工程
·
再生医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Meng Zhang,Yumei Wang,Jiayi Wang,Jiayi Zuo,Feng Jiang,Feng Cao
Neovascular ocular diseases are a leading cause of irreversible vision loss. Although intravitreal anti-VEGF therapy is the standard treatment, its invasive delivery and limited efficacy in some patients emphasize the need for non-invasive strategies targeting multiple angiogenic pathways. In this study, we developed a novel hybrid nanoplatform for the non-invasive co-delivery of axitinib (Axi) and telmisartan (Tel) to synergistically inhibit both VEGF and Ang-2 signaling pathways. Poorly soluble drugs were incorporated into layered double hydroxides (LDHs) via a micelle-assisted intercalation strategy and subsequently modified with hyaluronic acid (HA) conjugated to Gly-Val-Sar (GVS), a novel PepT1-targeted tripeptide. The Zn-containing LDH provided controlled drug release, and exhibited anti-inflammatory properties. HA modification prolonged ocular retention, and GVS enhanced transmembrane transport. The resulting Axi/Tel-D@LDH-HA-GVS nanocomposites demonstrated favorable physicochemical properties, efficient uptake by human conjunctival and retinal pigment epithelial cells, and potent inhibition of hypoxia-induced angiogenesis in vitro. In vivo, the formulations exhibited prolonged ocular retention, effective posterior tissue distribution, and good biosafety. In a diabetic retinopathy model, Axi/Tel-D@LDH-HA-GVS nanocomposites restored retinal structure and markedly reduced the expression of VEGF, Ang-2, TNF-α, and IL-6. Collectively, this study provides a promising non-invasive and synergistic strategy for targeted treatment of ocular neovascular diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL PHYSICS
·
2019
·
IF 1.822
Xin-Qi Zhou,Bao-Li Wang,Song-Bo Kou,Zhen-Yi Lin,Yan-Yue Lou,Kai-Li Zhou,Jie-Hua Shi
Intermolecular interaction of telmisartan (TMST), an angiotensin II receptor antagonist with bovine serum albumin was explored in vitro by the means of multi-spectral approaches such as UV absorption, stead-state fluorescence, synchronous fluorescence, 3-D fluorescence, and infrared spectroscopies in combination with theoretical calculation. The UV absorption and steady-state fluorescence studies manifested that BSA interacted with TMST leading to the fluorescence of both BSA and TMST were quenched through a static quenching manner. It can be found that a TMST-BSA complex with the stoichiometric ratio of 1:1 was formed and the binding constant ( K b ) was 7.26 × 10 3 M −1 at 298 K(close to 10 4 M −1 ), suggesting TMST was a moderate affinity on BSA, and its value diminished with the rising temperature, predicating the binding interaction of TMST with BSA was an exothermic reaction. The results from the competitive exploration and molecular modeling have confirmed that TMST primarily inserted into the hydrophobic cavity between sub-domain IIA and IIB of BSA. The calculated Δ H and Δ S values on the base of van't Hoff equation were −40.02 kJ·mol −1 and −60.46 J·mol −1 ·K −1 , meaning that hydrogen bonds and van der Waals force played dominating roles in the TMST–BSA system. The results of FT-IR spectra suggested that the alteration in the secondary structure of BSA like the decline in the contents of α-helix and β-sheets and the increase in the random coil. Meantime, the obvious variety in the configuration of TMST occurred after binding to fit the configuration of binding pocket.
研究领域:
生物化学
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生物物理
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药学
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分子生物学
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光谱学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Liu Tao,Cui Lijuan,Xue Huan,Yang Xiaohua,Liu Mengmeng,Zhi Linping,Yang Huanhuan,Liu Zhihong,Zhang Min,Guo Qing,He Peifeng,Liu Yunfeng,Zhang Yi
Angiotensin II type 1 (AT1) receptor blockers (ARBs), as antihypertensive drugs, have drawn attention for their benefits to individuals with diabetes and prediabetes. However, the direct effects of ARBs on insulin secretion remain unclear. In this study, we aimed to investigate the insulinotropic effect of ARBs and the underlying electrophysiological mechanism. We found that only telmisartan among the three ARBs (telmisartan, valsartan, and irbesartan) exhibited an insulin secretagogue role in rat islets. Independent of AT1 receptor and peroxisome proliferator-activated receptor γ (PPARγ), telmisartan exerted effects on ion channels including voltage-dependent potassium (Kv) channels and L-type voltage-gated calcium channels (VGCCs) to promote extracellular Ca2+ influx, thereby potentiating insulin secretion in a glucose-dependent manner. Furthermore, we identified that telmisartan directly inhibited Kv2.1 channel on a Chinese hamster ovary cell line with Kv2.1 channel overexpression. Acute exposure of db/db mice to a telmisartan dose equivalent to therapeutic doses in humans resulted in lower blood glucose and increased plasma insulin concentration in OGTT. We further observed the telmisartan-induced insulinotropic and electrophysiological effects on pathological pancreatic islets or β-cells isolated from db/db mice. Collectively, our results establish an important insulinotropic function of telmisartan distinct from other ARBs in the treatment of diabetes.
研究领域:
药理学
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内分泌学
·
糖尿病
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电生理学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 23
·期 3
·1-8
·
IF 2.751
Qian Liu,Ruoyi Wang,Nan Ma,Chuntian Wang,Weixiu Chen
Hypertension is associated with bladder symptoms. The present study investigated whether an angiotensin receptor blocker could improve the symptoms and pathological changes associated with a neurogenic bladder (NB). A Sprague‑Dawley rat model of NB was constructed. Rats in the sham and model groups were gavaged with saline, and rats in the treatment group were gavaged with telmisartan. Urodynamic parameters, including maximum cystometric capacity, residual urine volume, bladder wet weight, bladder compliance and detrusor pressure, were detected. Masson and H&E staining were performed to assess bladder fibrosis and histopathological changes. The expression levels of basic fibroblast growth factor (bFGF), TGF‑β1, Collagen I, Collagen III, and α‑smooth muscle actin (α‑SMA) were also measured by reverse transcription‑quantitative PCR, western blotting and immunohistochemistry. The model rats exhibited symptoms and pathological changes associated with NB. Treatment with telmisartan reduced maximum cystometric capacity, residual urine volume, bladder compliance and bladder wet weight, and increased detrusor pressure in model rats. The tissue staining results showed that telmisartan exerted an antifibrotic effect. In addition, telmisartan inhibited the expression of bFGF, TGF‑β1, Collagen I, Collagen III and α‑SMA in model rats. Therefore, the results of the present study indicated that telmisartan may serve as a potential therapeutic agent for NB.
研究领域:
药理学
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泌尿外科
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病理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Lu Xu,Qin Zhao,Yiqiong Xie,Ge Bai,Hongwen Liu,Qi Chen,Hongjue Duan,Lishan Wang,Hang Xu,Yuxiang Sun,Gao Ling,Weihong Ge,Yun Zhu
Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.
研究领域:
药理学
·
胃肠病学
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生物医学工程
·
炎症
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产品关联
DOI
PubMed
高影响因子
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