CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yao Xiong,Tianshun Wang,Lei Liu,Yuanqi Kou,Zhengyu Zhao,Min Yuan,Yan Chen,Dan Wang,Shiyong Song
D-ɑ-tocopheryl poly(ethylene glycol)1000 succinate (TPGS) has been extensively applied in drug delivery systems for its amphiphilic property and inherent bioactivity. But TPGS has not always been utilized solely for the unstability of TPGS micelle. Inspired by the hydrogels made from other amphiphilic molecules, thermosensitive TPGS hydrogels were firstly discovered and developed in the presence of specific anions, which self-assembled from the aggregation of TPGS micelles stimulated by heating and salting-out effect. Subsequently, hydrophobic doxorubicin (DOX) loaded TPGS micelles were likewise prepared and converted into DOX loaded hydrogel with the help of β-Glycerol phosphate disodium (β-GP). It was found that the amount of TPGS and β-GP in the solution considerably affected the gelation time and critical temperature. One of the formulations containing 4 wt% TPGS and 15 wt% β-GP was selected due to its appropriate gelation time and temperature for subcutaneously injection. Pristine and drug-loaded TPGS hydrogels were explored for their potential values in clinic applications. Derived from the bioactivity of TPGS, the pristine TPGS hydrogel exhibited a certain tumor inhibiting efficiency comparable to the DOX-containing formulations. And the efficiency of DOX-loaded TPGS hydrogels were dosage-dependent and superior to systemically administrated free DOX, which demonstrated a synergistic effect between DOX and TPGS hydrogel. In short, this study developed a multifunctional injectable hydrogel and provided a new synergetic strategy for tumor therapy.
研究领域:
药剂学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Xiumei Zhu,Altansukh Tsend-Ayush,Zhongyue Yuan,Jing Wen,Jiaxin Cai,Shifu Luo,Jianxu Yao,Junxing Bian,Linfang Yin,Jianping Zhou,Jing Yao
In this study, glycyrrhetinic acid (GA)-modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs) displayed a mean particle size of 133.6 ± 1.2 nm with a low poly-dispersity index (0.224 ± 0.013) and negative zeta potential (−16.30 mV). The drug loading and entrapment efficiency of ETO-TGA PMs were 10.4% and 79.8%, respectively. ETO-TGA PMs also exhibited faster drug release behavior at pH 5.8 and relatively stable drug release at pH 7.4. Confocal laser scanning microscope (CLSM) observations and in vivo imaging studies revealed that TGA PMs displayed higher cellular uptake and selective accumulation at the tumor site, indicating good tumor targetability. Furthermore, ETO-TGA PMs displayed significant cytotoxicity towards HepG2 cells and higher anti-tumor efficacy (75.96%), compared to the control group. This could be due to TGA-mediated targeted drug delivery to the hepatocytes as well as P-gp inhibition. These findings suggest that TGA PMs have the potential to be used as a targeted drug delivery system for hepatic cancer therapy.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2013
·
IF 3.458
Pengfei Xu,Qi Yin,Jianan Shen,Lingli Chen,Haijun Yu,Zhiwen Zhang,Yaping Li
Tumor metastasis is the leading cause of breast cancer-related mortality and remains to be the principal obstacle for the successful chemotherapy of breast cancer . To block metastasis of breast cancer, silibinin-loaded lipid nanoparticles (SLNs) containing TPGS and phosphatidylcholine were designed and prepared by a thin-film hydration method. The optimized SLNs were approximately 45 nm in particle size with high stability in serum, which were further demonstrated to be efficiently uptaken by MDA-MB-231 breast cancer cells. Importantly, the SLNs could accumulate within tumor tissues with high efficiency and amounts. Compared with free silibinin , SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells through the downregulation of MMP-9 and Snail. More importantly, systematic in vivo evaluations demonstrated that SLNs treatment group resulted in 67% and 39% less pulmonary metastases formation than saline treatment group in the spontaneous and blood vessel metastasis models, respectively. Interestingly, the blank lipid nanoparticles without silibinin were also found, for the first time, to possess the efficient anti-metastatic capabilities to some extent. The biocompatibility assay reveals that SLNs treatment did not exhibit obvious systemic toxicity in two mouse models. Therefore, SLNs are the promising delivery systems against metastasis of breast cancer cells.
研究领域:
肿瘤学
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药剂学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Drug Delivery
·
2024
·Vol. 22
·期 4
·479-491
·
IF 2.8
Teng Guo,Chenming Zhang,Yuling Chen,Yihan Wu,Zhenda Liu,Yongtai Zhang,Nianping Feng
BackgroundAdding a suitable surfactant can enhance the transdermal permeability of transethosomes while also leveraging its functionality as a functional material. In this study, transethosomes were prepared using D-α-tocopherol acid polyethylene glycol succinate (TPGS) as edge activators for transdermal delivery of curcumin (Cur).MethodsThe TPGS-mediated curcumin-loaded transethosomes (Cur@TES) were prepared and formulated optimally, and the optimized formulations were characterized for their morphology, particle size, entrapment efficiency (EE) and drug loading (DL). The stability and deformability of Cur@TES were investigated, while the transdermal delivery of Cur@TES was investigated through in vitro transdermal assays and fluorescence imaging. A mouse ear swelling model was performed to determine the anti-inflammatory effect of Cur@TES.ResultsCur@TES appeared round or elliptical in shape. The particle size, EE and DL for the optimized formulation were observed as 131.2 ± 7.2 nm, 97.68 ± 2.26%, and 6.58 ± 0.62%, respectively. X-ray diffraction analysis confirmed the formation of disordered structures in the inner core of the vesicles. Moreover, Cur@TES system demonstrated better stability and deformability compared to the curcumin-loaded ethosomes (Cur@ES). In vitro transdermal experiments demonstrated that Cur@TES significantly increased the amount of drug retained in the skin (P<0.05). Fluorescence imaging confirmed that the skin distribution was distinctly enhanced with the delivery by TPGS mediated transethosomes. In addition, Cur@TES showed a significant inhibitory effect on Inflammatory swelling in the mouse ear-swelling model.ConclusionTPGS-mediated transethosomes exhibit significant transdermal advantages and enhanced anti-inflammatory effects, providing a new perspective for the transdermal delivery of curcumin.
研究领域:
药剂学
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生物医学工程
✓ 已验证
DOI
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
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2024
·Vol. 27
·期 1
·1-14
·
IF 2.1
Li Tingyuan,Li Jiaying,Wang Qilong,Gong Mingjie,Wang Xiaowen,Jiang Xia,Hua Qinyang,Ji Hao,Toreniyazov Elmurat,Yu Jiangnan,Cao Xia,Adu-Frimpong Michael,Xu Ximing
Isorhamnetin (ISO) is a kind of flavonoid widely found in sea buckthorn, ginkgo biloba, and other plants. It has many pharmacological activities, but poor solubility in aqueous media has limited its clinical application. In order to increase the bioavailability of ISO, we employed a thin film dispersion method to prepare ISO-loaded Soluplus-TPGS mixed polymer micelle (ISO-STM) and subsequently conducted appropriate characterizations. The micelles prepared in this work were spherical nanoparticles with uniform distribution with respective particle size (PS) and dispersion coefficient (PDI) of 81.62 ± 1.23 nm and 0.115 ± 0.020. Meanwhile, the encapsulation rate (EE) was 91.37% ± 0.82%, whereas the drug loading (DL) was 5.91% ± 0.06%. Compared to free ISO, the dissolution rate of mixed micelles (MM) significantly increased in three media. After oral administration, the oral bioavailability of MM was nearly 3 times higher than free ISO’s. In addition, the results of the zebrafish experiment showed that the anti-aging of zebrafish in the administration group was significantly better than that in the model control group. In summary, ISO-STM is a promising method with the potential to improve the solubility, and bioavailability and enhance the clinical application value of ISO.
研究领域:
药剂学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Drug Delivery and Translational Research
·
2020
·Vol. 11
·期 3
·1119-1132
·
IF 2.664
Li Xuefei,Fang Jingwang,Xin Meng,Li Qiqi,Wang Jun,Yang Hui,Wu Xianggen
Nimodipine (NMD), a calcium channel blocker, has demonstrated benefits in treating glaucoma. However, its ocular therapeutic application remains limited due to its poor aqueous solubility, which restrains the development of an ophthalmic formulation. Thus, the present study aimed to formulate an NMD micelle ophthalmic solution to enhance the potential of NMD in an ocular topical formulation to treat glaucoma. The NMD micelle ophthalmic solution was formulated with nanocarriers composed of rebaudioside A and d -α-tocopheryl polyethylene glycol 1000 succinate. Spherical mixed micelles were optimized and obtained at a small micelle size 13.429 ± 0.181 nm with a narrow size distribution (polydispersity index 0.166 ± 0.023) and high encapsulation efficiency rate (99.59 ± 0.09%). Compared with free NMD, NMD in micelles had much greater in vitro membrane permeability and antioxidant activity. The NMD micelle ophthalmic solution was well tolerated in rabbit eyes. It profoundly improved the in vivo intraocular permeation of NMD, and in vivo intraocular pressure reduction and improved miosis were also observed. Accordingly, this NMD micelle ophthalmic solution might be a promising ocular formulation to treat glaucoma.
研究领域:
药剂学
·
眼科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2020
·
IF 3.99
Qinfu Zhao,Xian Li,Junya Lu,Yixuan Liu,Luping Sha,Donghua Di,Siling Wang
Thermo-chemotherapy could improve the therapeutic effects of single chemotherapy with the help of cytotoxic heat produced by the PTT (photothermal therapy). The photothermal conversion property of material needs to be preferentially considered in the design the drug delivery in the thermo-chemotherapy. Therefore, in this work, mesoporous carbon nanoparticles (MCN) with excellent heat generating efficiency and high surface area was designed. And the NIR absorbing dye cypate was conjugated on the surface of MCN by the cleavable disulfide bonds to hinder the premature release of doxorubicin (DOX) and enhance the photothermal properties of MCN-based delivery systems. And then TPGS was further covered on the surface of MCN by hydrophobic force to prolong circulation time and improve the biocompatibility and dispersion stability of MCN-CyT in physiological environment. The release of DOX accelerated obviously in the presence of glutathione (GSH), acidic condition and NIR irradiation, indicating that DOX/MCN-CyT exhibited redox/pH/NIR triple-triggered drug release. The anti-tumor experiment indicated that DOX/MCN-CyT showed a synergistic thermo-chemotherapy effect for cancer. Thus, the present research provides huge potential in multi-triggered drug delivery and thermochemotherapy for combination therapy.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 20
·4259-4271
·
IF 4.726
Chunhuan Shi,Zhiqing Zhang,Fang Wang,Xiaoqing Ji,Zhongxi Zhao,Yuxia Luan
There are two major hurdles for the current anti-cancer drug delivery systems. One is the emergence of multidrug resistance (MDR) and the other is the conflict between long-circulation and cellular uptake. In the present study, the anticancer drug docetaxel (DTX) was successfully loaded into three series of micelles via self-assembly using a mixture of PEO–PPO–PCL and D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS), for the purpose of prolonging the blood circulation time as well as overcoming MDR of DTX. Three series of copolymers with different PCL molecular weights, PEO68–PPO34–PCL9, PEO68–PPO34–PCL18 and PEO68–PPO34–PCL36, were synthesized. The prepared spherical mixed micelles (MM) were found to possess nanoscale size (25–135 nm). The PEO–PPO–PCL/TPGS mixed micelles had a low critical micelle concentration (∼10−6 g mL−1) and a low hemolysis rate (<5%), which has proved that they are safe for use in vivo. Moreover, they had obvious sustained release behavior in vitro and a longer circulation time than free DTX in vivo. The P-gp inhibition assay, cellular uptake and MTT assay in cancer cells exhibited that DTX-loaded MM could overcome MDR, show higher cellular uptake and higher antitumor efficacy than free DTX. The IC50 values demonstrated that the three series of DTX-loaded MM were 69, 82 and 100 fold effective than free DTX after 72 h treatment with MCF-7 cells, respectively. Therefore, these results demonstrated that the prepared DTX-loaded MM provide desirable application in cancer chemotherapy.
研究领域:
药学
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肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2021
·Vol. 22
·期 4
·1-10
·
IF 3.246
Yang Liuhong,Wu Penghui,Xu Jinchao,Xie Dihuan,Wang Zhongqing,Wang Qian,Chen Yong,Li Chuan Hua,Zhang Jiaxin,Chen Hangping,Quan Guilan
Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilast ’ s low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its C max and AUC last were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.
研究领域:
药剂学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Muhammad Asim Farooq,Huang Xinyu,Amna Jabeen,Anam Ahsan,Theodora Amanda Seidu,Perpetua Takunda Kutoka,Bo Wang
Vorinostat (VOR) is known as one of the histone deacetylase inhibitors (HDACi) for cancer treatment, and the FDA approves it for cutaneous T cell lymphoma therapy. Poor solubility, permeability, and less anti-cancer activity are the main challenges for the effective delivery of VOR against various cancers. So, our team assumed that the surface-coated liposomes might improve the physicochemical properties of biopharmaceutics classification system class IV drugs such as VOR. The present study aimed to enhance the cytotoxicity and improve cellular uptake using TPGS-coated liposomes in breast cancer cells. Liposomes were fabricated by the film hydration following the probe ultra-sonication method. OR-LIPO and TPGS-VOR-LIPO showed an average particle size of 211.97 ± 3.42 nm with PDI 0.2168 ± 0.006 and 176.99 ± 2.06 nm with PDI 0.175 ± 0.018, respectively. TPGS-coated liposomes had better stability and revealed more than 80 % encapsulation efficiency than conventional liposomes. Transmission electron microscopy confirmed the TPGS coating around liposomes. Moreover, TPGS-coated liposomes enhanced the solubility and showed sustained release of VOR over 48 h. DSC and PXRD analysis also reveal an amorphous state of VOR within the liposomal formulation. MTT assay result indicates that the superior cytotoxic effect of surface-modified liposomes contrasts with the conventional and free VOR solution, respectively. Fluorescence microscopy and flow cytometry results also presented an enhanced cellular uptake of TPGS-coated liposomes against breast cancer cells, respectively. The current investigation's final results declared that TPGS-coated liposomes are promising drug carriers for the effective delivery of hydrophobic drugs for cancer therapy.
研究领域:
药学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MICROENCAPSULATION
·
2019
·
IF 2.04
Chunmei Wei,Qilong Wang,Wen Weng,Qiuyu Wei,Yujiao Xie,Michael Adu-Frimpong,Elmurat Toreniyazov,Hao Ji,Ximing Xu,Jiangnan Yu
This study was designed to investigate the bioavailability and targeting of myricetrin-loaded ternary micelles modified with and without TPGS. The particle diameters of myricetrin-loaded micelles and myricetrin-loaded-TPGS micelle were 30.93 ± 1.34 nm and 26.42 ± 0.89 nm, respectively, while their respective encapsulation efficiencies (m/m, %) were 83.3 ± 1.08 and 93.8 ± 1.18. The release rate of myricetrin in the micellar system clearly exceeded the free myricetrin in the three media (pH 6.8 phosphate buffer, pH 1.2 HCl solution and double distilled water). In vivo studies displayed that the bioavailability of myricetrin mixed micelles was remarkably improved than the free drug after oral administration. Moreover, the results of tissue distribution showed that myricetrin-loaded-TPGS micelles accumulated well in the liver tissue. Based on these results, it was speculated that myricetrin-loaded-TPGS micelles might act as a promising carrier for liver targeting with improved hepatic concentration of myricetrin compared with the myricetrin-loaded micelles.
研究领域:
药学
·
药物动力学
·
药物递送系统
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Jian Liu,Qilong Wang,Michael Adu-Frimpong,Qiuyu Wei,Yujiao Xie,Kangyi Zhang,Chunmei Wei,Wen Weng,Hao Ji,Elmurat Toreniyazov,Ximing Xu,Jiangnan Yu
Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS . Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ± 0.9 nm , high EE of 97.33 ± 0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC 0-24h) of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）