DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2018
·
IF 1.883
Cheng Hu,Kun Liang,Rui An,Xinhong Wang,Lisha You
Objective: The objective of this study (ARS-TPGS-Lipo) was to enhance the stability, encapsulation efficiency (EE), improve AUC, circulation time and liver targeting of ARS-TPGS-Lipo.Methods: ARS-TPGS-Lipo was prepared by thin-film dispersion method and characterized by TEM. The EE, in vitro release and stability of ARS-TPGS-Lipo were detected by HPLC and UV. In addition to the safety evaluation, the pharmacokinetics and tissue distribution studies were also carried out after i.v. administration.Results: The size, PDI, zeta potential, and EE of ARS-TPGS-Lipo were 126.7 ± 9.9 nm, 0.182 ± 0.016, −10.1 ± 1.43 mV, and 78.8 ± 1.89%, respectively. ARS-TPGS-Lipo showed the slow-release effect in vitro release experiments. The AUC of ARS in the ARS-TPGS-Lipo group was 7.51 times higher than in the ARS group after i.v. administration and the circulation time was significantly prolonged. The tissue distribution results showed the components of artesunate and its metabolism DHA of the ARS-TPGS-Lipo group were much higher in liver than the ARS-Lipo group.Conclusion: ARS-TPGS-Lipo was prepared successfully, which had the smaller vesicles size with a better PDI, better stability, higher EE, and slow-release. The results of safety evaluation indicated that ARS-TPGS-Lipo had no hematotoxicity and hepatorenal toxicity. The pharmacokinetic studies indicated ARS-TPGS-Lipo had higher AUC, longer circulation time and better liver targeting.
研究领域:
药剂学
·
药物代谢动力学
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2018
·
IF 2.082
Yude Liu,Lian Rao,Hongguan Zhang,Yanyou Cen,Kaili Cheng
Herb borneol is usually used in clinics for the treatment of central nervous system illness, for its ability of blood–brain barrier permeability, although its poor water solubility and poor bioavailability limit its clinical application to some degree. In this study, we developed a novel nanoparticle combining the benefits of vitamin E d-ɑ-tocopheryl poly(ethylene glycol) succinate (E-TPGS) (or TPGS) and guar gum to get TPGS-g-guar gum as a drug delivery system to carry borneol, which could improve the solubility of borneol and increase the drug-loading capacity efficiently. The results showed that TPGS-g-guar gum nanoparticles delivery system was suitable to carry borneol and release the drug effectively, and TPGS-g-guar gum/borneol nanoparticles would be a potential platform for improving the treatment of central nervous system illness and cerebrovascular disease.
研究领域:
药剂学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Meng Tong,Xiaoyan Wu,Shuya Zhang,Di Hua,Shukun Li,Xiangyu Yu,Jing Wang,Zhenhai Zhang
The oral bioavailability and efficacy of baicalein is dramatically limited by its low solubility and effect of efflux. In our study, we chose PVP-VA64 as a carrier and TPGS as a plasticizer and efflux inhibitor to prepare a solid dispersion of baicalein using hot-melt extrusion technology to improve its solubility and bioavailability. The hot-melt process and formulation were optimized, and a BAC-PVP VA64-TPGS solid dispersion (BPT-SD) was prepared. BAC exists in an amorphous or molecular state in BPT-SD. BPT-SD comprised irregular lumps and small particles without BAC or carrier characteristics. The dissolution efficiency of BPT-SD improved under sink conditions. FTIR showed a strong hydrogen bond between BAC and PVP-VA64 in BPT-SD. BPT-SD maintained good physical stability for 6 months. The apparent permeability coefficient of BAC in the Caco-2 cell model confirmed that BPT-SD had higher gastrointestinal membrane permeability. A rat pharmacokinetic study showed that BPT-SD had higher C max and AUC 0- 24h, shorter T max , and 2.88-fold higher bioavailability than BAC. A behavioral experiment in chronic unpredictable mild stress (CUMS) mice confirmed the antidepressant efficacy of BAC. BPT-SD reversed depression-like behavior in CUMS mice and improved BAC bioavailability. BAC preparation into a solid dispersion significantly enhanced dissolution performance and bioavailability.
研究领域:
药剂学
·
生物医学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2020
·
IF 2.169
Lijun Zhen,Qiuyu Wei,Qilong Wang,Huiyun Zhang,Michael Adu-Frimpong,Caleb Kesse Firempong,Ximing Xu,Jiangnan Yu
6-Gingerol, an active herbal ingredient of ginger has various bioactivities such as anti-neurodegenerative disease, anti-inflammatory and so on. The aim of the present study was to enhance the oral bioavailability and brain distribution of 6-Gingerol via polymeric micelles. A polymeric micelles drug delivery system of 6-Gingerol consisting of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poly (ethylene glycol)-poly (ε-caprolactone) (PEG-PCL) was prepared via solvent injection method. The developed 6-Gingerol-loaded TPGS/PEG-PCL micelles (6-GTPMs) were characterized based on particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), drug loading (DL) and in vitro release profile. The pharmacokinetics and tissue distribution studies were also evaluated. The nanoformulation produced a particle size of 73.24 ± 2.84 nm with acceptable PDI (0.129 ± 0.03), zeta potential (−2.74 ± 0.92 mV), DL (4.64%) and EE (79.68%). The in vitro release profile showed that the 6-GTPMs enhanced the solubility of 6-Gingerol, while the pharmaceutical analysis in rats indicated that 6-GTPMs significantly improved the oral bioavailability of 6-Gingerol (about 3 folds) in circulation. The 6-GTPMs exhibited remarkable brain targetability in the tissue distribution analysis. Collectively, a 6-Gingerol polymeric micelle with enhanced oral bioavailability coupled with excellent brain distribution was successfully developed.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 63
·期 2
·68-74
·
IF 1.164
Wen Lv,Lihua Cheng,Baohua Li
One of the major obstacles to successful paclitaxel (PTX) chemotherapy is toxic side effects, which are often due to the conventional surfactants used, such as Cremophor EL. PTX is characterized by its hydrophobicity and insolubility, which limit its application in ovarian cancer therapy. The aim of this study was to develop Cremophor EL-free PTX-loaded methoxy poly(ethylene glycol)-block-(lactic-co-glycolic acid) copolymers (PLGA-mPEG) nanoparticles (NPs) using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a novel emulsifier. The ability of nanoparticles loaded with paclitaxel (NP-PTX) to inhibit tumor growth was assessed in vitro and in vivo. The acute toxicity of NP-PTX was also evaluated in vivo. We found that paclitaxel was efficiently encapsulated into PLGA-mPEG NPs with a low concentration of TPGS as the emulsifier. The synthesized NP-PTX demonstrated the desired diameter of 80 nm as characterized by transmission electron microscopy. The NP-PTX also exhibited a sustained release of loaded PTX over 4 d with the same chemotherapeutic efficiency and reduced side effects. NP-PTX-treated cells showed slightly lower cytotoxic responses compared with those treated with free PTX at the same concentration. In vivo studies confirmed that NP-PTX significantly enhanced the median lethal dose of paclitaxel by 10-fold, and a similar effect on the inhibition of tumor growth was achieved in nude mice.
研究领域:
药剂学
·
肿瘤学
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DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2024
·Vol. 20
·期 9
·1457-1466
·
IF 2.9
Shi Feng,Sun Weigang,Yin Wenxiong,Xia Xiaoli,Adu-Frimpong Michael,Cao Xia,Ji Hao,Wang Qilong,Xu Ximing,Yu Jiangnan
In this study, Esculin (ES)-loaded liposomes modified with TPGS (ES-TPGS-Ls) were successfully prepared to enhance bioavailability and hepatoprotective activity of this coumarin glucoside. We utilize thin-film dispersion to fabricate ES-TPGS-Ls. The size, polydispersed index (PDI),
Zeta potential (Z-potential), morphology, and encapsulation effectiveness of the liposomes were all evaluated afterwards. The storage stability of ES-TPGS-Ls at 4 °C was investigated. The findings showed that ES-TPGS-Ls had spherical nanoparticles with 194.47±8.54 nm as the mean
size, 0.239±0.011 as PDI, and −21.16±0.97) mV as Z-potential coupled with encapsulation efficiency (EE) of 91.85±0.44%. Storage stability of liposomes at 4 °C was maintained within one week. Pharmacokinetic study showed that the relative oral bioavailability
of ES-TPGS-Ls increased by 2.38 times. Pharmacodynamic studies showed that the developed liposomes could enhance the hepatoprotective activity of ES. Overall, the ES-TPGS-Ls significantly enhanced the bioavailability of esculin, thereby enhancing the in vivo hepatoprotective effect
of ES.
研究领域:
药剂学
·
药物代谢动力学
·
肝脏保护研究
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DOI
高影响因子
JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY
·
2023
·
IF 2.2
Junwei Liu,Meihong Zhang,Chuanbin Wu,Xin Pan,Zhengwei Huang
Erastin is the most classical small molecular ferroptosis inducer but its clinical application is hindered due to its poor solubility. Nanotechnology has been used to improve ferroptosis inducer erastin’s solubility. The recently reported erastin-incorporated nanosystems (e.g., nanoparticulate ferritin, poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (mPEG-PLGA) nanoparticle, exosome, and liposome) could to some degree elevate its solubility, but were still poor in loading capacity. To be specific, the maximum entrapment efficiency and drug loading in previous studies were approximately 36% and 3.7%, respectively. In order to improve drug loading capacity, we constructed a novel carrier based on Vitamin E d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) blended micelles. The erastin@TPGS/Soluplus® micelles were prepared by thin film hydration method, and formulation details including dosage of Soluplus®, the weight ratio of TPGS to Soluplus®, the weight ratio of erastin to TPGS/Soluplus® were optimized. The physicochemical properties of the erastin micelles were measured by DLS, TEM, FTIR, and TG-DSC analysis. The products exhibited a nanoscale and uniform particle size (78.11 ± 0.54 nm) and neutral surface charge (-0.43 ± 0.32 mV). Significantly improved entrapment efficiency (89.63 ± 1.81%) and drug loading rate (10.03 ± 0.14%) were obtained, which was over 2-fold of current reports. The in vitro release study demonstrated that erastin could release in a sustained yet complete manner, and the drug release might be governed by multiple mechanisms including anomalous diffusion of non-Fickian diffusion, matrix erosion and sustained release. In summary, this proposed erastin nanosystem provides a new strategy for improving loading capacity, and may probably augment ferroptosis-inducing therapy for cancer treatment.
研究领域:
药学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Conglian Yang,Yuting Qin,Kun Tu,Chenfeng Xu,Zhen Li,Zhiping Zhang
Multidrug resistance (MDR) remains as an obstacle for effective cancer treatment. Herein, we developed a novel and efficient nanomedicine by virtue of the carrier characters and MDR inhibition effects of β-cyclodextrin (β-CD) and d-α-tocopheryl polyethylene glycol succinate (TPGS). A series of star-shaped polymers CD-g-TPGS with different TPGS substitution degree were synthesized for doxorubicin (DOX) delivery, where β-CD was identified as a core and TPGS as branches. These star polymers can self-assemble into nanoparticles with DOX . These nanoparticles showed no significant differences in size, zeta potential and morphology except for in vitro stability. They demonstrated good biocompatibility and enhanced cellular uptake in both drug sensitive and resistant cancer cells. Notably, the nanoparticles exhibited superiority of cytotoxicity in drug resistant cancer cells against free DOX . In vivo antitumor effect also demonstrated the improved cancer inhibition effect. This work suggests that star-shaped polymers CD-g-TPGS are promising drug carriers to overcome MDR in cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
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DOI
高影响因子
COLLOID AND POLYMER SCIENCE
·
2019
·Vol. 297
·期 10
·1321-1330
·
IF 1.906
Chen Jun,Ding Amin,Zhou Yifeng,Chen Pengpeng,Xu Ying,Nie Wangyan
Star-shaped copolymers based on star-shaped poly (L-lactide) (s-PLLA) and tocopheryl polyethylene glycol 1000 succinate (TPGS) (s-PLLA-TPGS) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of s-PLLA-TPGS copolymers and their micelle properties. The structure and M w of s-PLLA-TPGS were characterized with 1 H NMR, GPC, DSC, and XRD. The indometacin(IMC)-loaded s-PLLA-TPGS micelles were obtained by dialysis method. The effects of arm numbers of s-PLLA-TPGS copolymers on surface morphology, particle size, zeta potential, drug loading content (LC), drug encapsulation efficiency (EE), and in vitro drug release behavior of prepared micelles were studied. The results indicated that the average diameters, LC, and EE of IMC-loaded s-PLLA-TPGS micelles gradually increased in the order of 4-arm, 5-arm, and 6-arm s-PLLA-TPGS copolymers. The in vitro release studies showed that the IMC accumulative release can be decreased by increasing the arm numbers of the s-PLLA-TPGS copolymers, and the release profiles of IMC from the s-PLLA-TPGS copolymers followed the Baker-Lonsdale model equation. The results suggest that the arm number regulation of s-PLLA-TPGS copolymers can provide a new strategy for designing drug carriers of high efficiency.
Graphical abstract
研究领域:
药剂学
·
材料科学
·
生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2021
·Vol. 23
·期 6
·1-16
·
IF 2.253
Wang Qilong,Liu Jing,Liu Jian,Thant Yaminn,Weng Wen,Wei Chunmei,Bao Rui,Adu-Frimpong Michael,Yu Qingtong,Deng Wenwen,Cao Xia,Toreniyazov Elmurat,Ji Hao,Xu Ximing,Yu Jiangnan
Recently, bisdemethoxycurcumin (BDMC), a constituent of turmeric, has been studied widely in view of their various therapeutic effects, namely anti-oxidant, anti-cancer, anti-diabetic, and anti-inflammatory. Since ancient times, turmeric has been extensively used as a naturally occurring traditional Chinese medicine (TCM) and as a crucial home remedy for treatment of many health problems such as inflammation and pain. However, the action of anti-gouty arthritis and analgesic activity of its constituents, especially BDMC, have not been scientifically reported yet. Despite the various bioactivities of BDMC, its utilization in clinics has been restricted owing to poor solubility and bioavailability. This research aimed at enhancing oral bioavailability and pharmacokinetic of BDMC via liposome formulation which was modified with d -α-tocopherol polyethylene glycol 1000 succinate (TPGS or vitamin E TPGS) and was characterized using various parameters both in vitro and in vivo. Also, the analgesic and anti-gouty activities of BDMC-loaded TPGS-modified liposomes were investigated by assessing pain threshold and serum uric acid level in potassium oxonate–induced hyperuricemic rats. As the result, BDMC-loaded TPGS-modified liposomes were formulated successfully with optimal physiochemical properties such as 75.98 ± 5.46 nm (particle size), 0.246 ± 0.011 (polydispersity index), − 38.21 ± 0.29 mV (zeta potential), 96.98 ± 0.17 (encapsulation efficiency (EE%)), and 4.84 ± 0.0089 (drug loading capacity (DL%)). Moreover, the oral bioavailability of liposomized BDMC was approximately 10-fold greater than free BDMC in vivo and in vitro cumulative release rates in pH 1.2 (78%) and pH 7 (68%) respectively. This significantly improved the sustaining drug effect of BDMC compared with free form. In addition, BDMC-TPGS liposome acted as a xanthine oxidase inhibitor to evidently reduce uric acid level in potassium oxonate–induced hyperuricemic rats and remarkably increase pain threshold capacity and reaction time in hot plate test at a dose-dependent manner. Altogether, BDMC-conjugated TPGS liposome could act as favorable nanocarriers against gouty arthritis and intense pain with prospect of overcoming the limitation of BDMC application.
研究领域:
药剂学
·
生物医学
·
中药学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 103
·100984-100992
·
IF 3.289
Mengshi Yang,Di Jiang,Zhilong Chen,Jun Chen
Photodynamic therapy (PDT) does well in both curing early stage tumors and improving patients’ quality of life. However, the limited selectivity of photosensitizers (PSs) to tumors has become an urgent issue during the application of PDT clinically, which would exhibit a poor therapeutic outcome and induce skin phototoxicity. To solve this problem, PS-loaded D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS, or simply TPGS) nanoparticles with tumor homing and penetrating peptide tLyp-1 decoration (t-NP) were constructed for PDT of tumors in this study. Verteporfin (VP), as an effective PS, was encapsulated in the core of t-NP, and tLyp-1 was functionalized on the surface as a functional ligand to increase vascular permeability and target the tumor cells. These nanoparticles were spherical in shape and exhibited a narrow size distribution of 23.3 ± 0.80 nm, and had a high encapsulation efficiency and loading capacity of hydrophobic VP. Compared with unmodified nanoparticles (NP), t-NP exhibited enhanced cellular uptake in both primary human umbilical vein endothelial cells (HUVECs) and drug-resistant human colon adenocarcinoma cells (HCT15); and t-NP showed higher selectivity to HCT15 tumors in vivo after intravenous administration of the same dose of VP. The anti-tumor experiment in vivo strongly indicated that nanoparticles with tLyp-1 peptide modification can enhance the selectivity of the PS, and improve the PDT effect.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
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产品关联
DOI
高影响因子
AAPS PHARMSCITECH
·
2019
·Vol. 20
·期 3
·1-10
·
IF 2.608
Liu Yingkun,Sun Congyong,Li Wenjing,Adu-Frimpong Michael,Wang Qilong,Yu Jiangnan,Xu Ximing
In this study, syringic acid–loaded TPGS liposome (SA-TPGS-Ls) was successfully prepared to improve oral bioavailability of syringic acid (SA). SA is a natural and notable antioxidant activity compound with its limited bioavailability ascribable to its poor aqueous solubility and fast elimination. Recently, TPGS has become a perfect molecular biomaterial in developing several carrier systems with sustained, controlled, and targeted the drug delivery. SA-TPGS-Ls was prepared via thin-film dispersion method and characterized in terms of particle size, stability, morphology, and encapsulation efficiency (EE). The results showed that SA-TPGS-Ls had regular spherical-shaped nanoparticles with EE of 96.48 ± 0.76%. The pharmacokinetic studies demonstrated a delayed MRT and prolonged t 1/2 , while relative oral bioavailability increased by 2.8 times. Tissue distribution showed that SA-TPGS-Ls maintained liver drug concentration while delayed elimination was also observed in the kidney. In CCl 4 -induced hepatotoxicity study, the activities of hepatic T-AOC, GSH-Px, CAT, GSH, and SOD were greatly elevated, while serum biological markers ALT, AST, and AKP were reduced after treatment of mice with SA-TPGS-Ls. Histopathological studies confirmed that SA-TPGS-Ls could remarkably improve the status of hepatic tissues. Collectively, SA-TPGS-Ls significantly improved the drug encapsulation efficiency, stability coupled with bioavailability of SA, hence increasing in vivo antioxidant activity of the drug.
研究领域:
药剂学
·
生物医学
·
药物代谢动力学
✓ 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）