Frontiers in Pharmacology
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2024
·
IF 4.4
Li Qing-qing,Yan Jia-hui,Zhou Zhi-e,Geng Xiang,Xiong Jian-hua
Introduction: Chlorogenic acid (CGA) has been identified to possess salient anti-inflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its anti-inflammatory activity.Methods: The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The in vitro release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism.Results: The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of INF-γ, IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65, while concomitantly upregulating the expression of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae, while decreasing the abundance of Bacteroidaceae, Rikenellaceae, and Helicobacteraceae.Conclusion: Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the anti-inflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis.
研究领域:
药学
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生物医学工程
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炎症研究
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DOI
PubMed
高影响因子
CHEMICAL PHYSICS LETTERS
·
2019
·
IF 1.901
Xiaoluan Lu,Wentao Zhu,Tingyu Chen,Qianrong Peng,Changmu Yu,Min Yang
A novel mixed micelles was developed to improve the solubility of Zinc phthalocyanine (ZnPc). Sodium deoxycholate (SDC) and D-alpha tocopheryl polyethylene glycol succinate (TPGS) were utilized as micelles material, mainly based on the design that ZnPc was located inside the hydrophobic core of mixed micelles, which was formed by supramolecular self-assembly of SDC and TPGS. A series of ZnPc loaded mixed micelles containing different quality of SDC were prepared and characterized by means of their physicochemical properties, photodynamic activity, photostability, drug release and cell viability. These mixed micelles appeared spherical, short rod and long rod shape, respectively, with corresponding particle sizes of about 106 nm, 344 nm and 80 nm, respectively. Drug loading efficiencies were higher than 90%. The capacity of ZnPc loaded mixed micelles to produce singlet oxygen ( 1 O 2 ) by irradiation with 650 nm red laser was monitored using 1,3-diphenylisobenzofuran as a probe. The singlet oxygen quantum yields ( Φ Δ ) for ZnPc loaded mixed micelles were high to that of the standard (ZnPc in DMF), and three of mixed micelles displayed excellent ability to generate 1 O 2 (the value of Φ Δ were greater than 0.70). These mixed micelles were photostable in the timescale typically used in photodynamic therapy (PDT), and only a small photobleaching event was observed after 20 min of light irradiation. The in vitro drug release studies of ZnPc loaded mixed micelles demonstrated a sustained release profile. Phototoxicity experiments in A549 cells showed that mixed micelles had higher toxicity than that of free ZnPc with the same concentration. Thus, the mixed micelles developed in this work are a promising strategy to be employed in delivery of ZnPc in PDT.
研究领域:
药学
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纳米技术
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光化学
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生物医学工程
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DOI
高影响因子
Theranostics
·
2019
·
IF 8.063
Xu-Qi Kang,Gao-Feng Shu,Sai-Ping Jiang,Xiao-Lin Xu,Jing Qi,Fei-Yang Jin,Di Liu,Yong-Hong Xiao,Xiao-Yang Lu,Yong-Zhong Du
The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared β-Ga 2 O 3 :Cr 3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga 2 O 3 ) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods : I-TPGS/Ga 2 O 3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga 2 O 3 /TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga 2 O 3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga 2 O 3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga 2 O 3 /TIG were finally evaluated using acute pneumonia mice. Results : It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga 2 O 3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo . Additionally, targeted delivery of I-TPGS/Ga 2 O 3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion : It is of great value to apply I-TPGS/Ga 2 O 3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.
研究领域:
药学
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生物医学工程
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微生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2018
·
IF 3.862
Bingchao Cheng,Hao Pan,Dandan Liu,Dongyang Li,Jinyu Li,Shihui Yu,Guoxin Tan,Weisan Pan
The purpose of this work was to develop a d -α-tocopherol polyethylene glycol 1000 succinate (TPGS) decorated nanodiamond (ND) system loading water-insoluble curcumin (ND/CUR/TPGS) to improve the colloidal dispersity and oral bioavailability of the preparation. CUR was physically loaded into ND clusters, then TPGS was coated to the ND/CUR complex forming amorphous nanostructure on the interparticle nanocage of the ND substrate. The formulation of the nanocomplexes was optimized using response surface methodology, and the optimal ND/CUR/TPGS showed small particle size (196.32 nm), high drug loading efficiency (81.59%) and core-shell structure. In vitro release study demonstrated that the nanocomplexes provided a sustained release behavior. The absorptive concentration of ND/CUR/TPGS was dramatically improved in total intestinal tract compared with CUR suspension, and the absorption was controlled by multiple transcytosis mechanisms. Furthermore, the pharmacokinetic studies demonstrated that ND/CUR/TPGS had significantly higher C max (4.50-fold), larger AUC 0–t (10.67-fold), and longer MRT 0–t (3.07-fold) in contrast with that of CUR suspension. Therefore, ND/CUR/TPGS presented great potential for oral delivery of insoluble and poorly permeable drugs.
研究领域:
药剂学
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纳米技术
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药物递送系统
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2020
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IF 3.616
Jiahui Sun,Jing Li,Qi Liu,Min Jiang,Mengjia Yang,Siwen Zhan,Tong Qiu,Kaiyong He,Xueqiong Zhang
This study aimed to develop, evaluate, and optimize the mPEG-PLA/vitamin E-TPGS mixed micelle drug delivery system to encapsulate celecoxib (CXB) and honokiol (HNK) for intravenous treatment of breast cancer. To this end, we formulated CXB-loaded mPEG-PLA/vitamin E-TPGS (PV-CXB) and HNK-loaded mPEG-PLA/vitamin E-TPGS (PV-HNK) mixed micelles and analyzed their characteristics. The 4T1 cell line was used for cytotoxicity determination and cellular uptake experiments, and for establishing a 4T1-bearing mouse model for histopathology, immunofluorescence, terminal deoxynucleotidyl transferase-mediated nick end labeling, and Western blot analysis . The synergistic effects of PV-CXB and PV-HNK combination therapy were investigated in vitro and in vivo using the coefficient of drug interaction values. The mean size of PV-CXB and PV-HNK prepared with optimal formulation was approximately 50 nm , with a spherical shape. PV-CXB and PV-HNK combination therapy exhibited cytotoxicity in 4T1 cells in vitro. However, the toxicity of PV-CXB and PV-HNK combination therapy was not apparent in normal tissues (heart, liver, spleen, lung, and kidney) in vivo and reduced the expression of collagen fibers in tumor tissues. Moreover, the combination therapy reduced the expression of tumor growth biomarkers (Foxp3, CD4, Gr-1, CD11b, CD31, Ki67, FoxM1, and VEGF). In addition, the tumor cell apoptosis rate reached 45.71 ± 0.62%. The combined treatment with PV-CXB and PV-HNK showed synergistic effect both in vitro and in vivo. Thus, the PV-CXB and PV-HNK drug delivery system could be used as a potential combination therapy for breast cancer .
研究领域:
药剂学
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肿瘤学
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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
Pharmaceuticals
·
2024
·Vol. 17
·期 4
·412
·
IF 4.3
Zicheng Zhong,Yanling Lan,Jinxing Chen,Lu Ping,Xuchun Li,Qing Wang,Xiaodong Zhuang,Zhenwen Qiu,Tianhui Yuan,Qiupin Guo,Long Xi,Qingguo Li,Dandong Luo
Supercritical anti-solvent fluidized bed (SAS-FB) coating technology has the advantages of reducing particle size, preventing high surface energy particle aggregation, improving the dissolution performance and bioavailability of insoluble drugs. The poor solubility of Biopharmaceutics Classification System (BCS) class IV drugs poses challenges in achieving optimal bioavailability. Numerous anti-cancer drugs including paclitaxel (PTX) belong to the BCS class IV, hindering their therapeutic efficacy. To address this concern, our study explored SAS-FB technology to coat PTX with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) onto lactose. Under our optimized conditions, we achieved a PTX coating efficiency of 96.8%. Further characterization confirmed the crystalline state of PTX in the lactose surface coating by scanning electron microscopy and X-ray powder diffraction. Dissolution studies indicated that SAS-FB processed samples release over 95% of the drug within 1 min. Moreover, cell transmembrane transport assays demonstrated that SAS-FB processed PTX samples co-coated with TPGS had an enhanced PTX internalization into cells and a higher permeability coefficient compared to those without TPGS. Finally, compared to unprocessed PTX, SAS-FB (TPGS) and SAS-FB processed samples showed a 2.66- and 1.49-fold increase in oral bioavailability in vivo, respectively. Our study highlights the efficacy of SAS-FB co-coating for PTX and TPGS as a promising strategy to overcome bioavailability challenges inherent in BCS class IV drugs. Our approach holds broader implications for enhancing the performance of similarly classified medications.
研究领域:
药剂学
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药物递送系统
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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
BMC Pharmacology & Toxicology
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2021
·Vol. 22
·期 1
·1-11
·
IF 2.483
Li Danni,Liu Shaogang,Zhu Jiahao,Shen Liqun,Zhang Qi ying,Zhu Hua
Background The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have anticancer properties, but doses at therapeutic levels have unacceptable side effects. Here we investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug. Methods Synthesized TPGS-FA was characterized by FTIR, UV-visible and 1 H NMR spectroscopy, and TPGS loaded with NC was evaluated for its ability to induce apoptosis in Huh7 cells by Annexin V/PI and MTT assays, and observed by laser scanning confocal microscopy and inverted phase contrast microscopy. Results TPGS-FA/NC complexes were prepared successfully, and were homogenious with a uniform size of ~ 14 nm diameter. NC was released from the TPGS-FA/NC complexes in a controlled and sustained manner under physiological conditions (pH 7.4). Furthermore, its cytotoxicity to hepatocarcinoma cells was greater than that of free NC. Conclusions TPGS-FA is shown to be useful carrier for drugs such as NC, and TPGS-FA/NC could potentially be a potent and safe drug for the treatment of hepatocellular carcinoma.
研究领域:
药学
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肿瘤学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2015
·
IF 3.65
Yanyun Xu,Haijing Meng,Fang Du,Wei Lu,Shiyuan Liu,Jin Huang,Jiahui Yu
Our recent publication showed that VES-dFdC nanocapsules in pure water could be obtained via the self-assembling of VES-dFdC prodrug synthesized by coupling gemcitabine (dFdC) with vitamin E succinate (VES). To prepare the intravenous injection nanoformulation, we present here a novel strategy to improve the stability and drug concentration of VES-dFdC nanoformulation in PBS or isotonic solution . Particularly, d -α-tocopheryl polyethylene glycol succinate (TPGS), usually used as drug solubilizer and coincidentally contains the same VES moiety as VES-dFdC prodrug and PEG chain, is selected to co-assemble with VES-dFdC prodrug. The zeta potentials of all the TPGS/VES-dFdC co-assemblies were close to 0 mV, and their particle size measured by dynamic light scattering (DLS) decreased from 113 to 36 nm with increasing TPGS/VES-dFdC molar ratios from 0.15 to 1.5. Stable colloidal suspensions were obtained without aggregates in PBS at 4 °C in one month or isotonic solution at 37 °C in one week, and the weight concentration of VES-dFdC prodrug increased from 7 to 17 mg/mL when the molar ratios of TPGS/VES-dFdC ranged from 0.5/1 to 1.5/1. The concentration of VES-dFdC prodrug was high enough to be used as intravenous injection nanoformulation in nude mice . Interestingly, along with the increase of TPGS/VES-dFdC molar ratios from 0.3/1 to 1.5/1, the morphology of TPGS/VES-dFdC co-assemblies changed from loose nanocapsule to compact micelle revealed by transmission electron microscope (TEM). Finally, the co-assembly of TPGS/VES-dFdC (TPGS/VES-dFdC: 1/1) was selected as intravenous injection nanoformulation to evaluate the antitumor activity . Compared with native dFdC, TPGS/VES-dFdC nanoformulation with 0.2 mmol/kg of dosage showed similar low toxicity in vivo , but 4.7 times high of tumor inhibition rate in nude mice with pre-established BxPC-3 tumors.
研究领域:
药学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Teng Guo,Jianying Lu,Yunlong Fan,Yongtai Zhang,Shuo Yin,Xianyi Sha,Nianping Feng
Combined therapy with anti-inflammatory drugs is preferred for the topical treatment of psoriasis , but the codelivery of drugs is restricted due to the lack of a suitable delivery system. Ethosomes with excellent transdermal properties are perfect as carriers for hyperplastic skin. Therefore, glycyrrhetinic acid-D-α-tocopherol acid polyethylene glycol succinate (GA-TPGS) was synthesized, which prevented the inflammation and lipid peroxidation damage, thus effectively stabilizing the psoriasis . Then GA-TPGS was surface-modified on the curcumin (Cur) loaded ethosomes to construct curcumin-loaded GA-TPGS-modified multifunctional ethosomes (Cur@GA-TPGS-ES), exerting synergistic treatment for psoriasis. Using an interleukin-6-induced cell model, we found that Cur@GA-TPGS-ES displayed desirable suppression of inflammation response and oxidative stress damage. Compared with the ethanol solution, the percutaneous penetration rates of Cur and GA in Cur@GA-TPGS-ES were superior. In vivo microdialysis revealed similar results, suggesting an increase of transcutaneous absorption in Cur@GA-TPGS-ES. Fluorescence staining revealed that the cellular uptake and skin distribution were distinctly enhanced with the delivery by Cur@GA-TPGS-ES. After topical administration to imiquimod-induced psoriatic mice, the Cur@GA-TPGS-ES group showed powerful treatment from inflammatory infiltration inhibition of Cur, glucocorticoid-like effects of GA and anti-lipid peroxidation of TPGS. Overall, GA-TPGS mediated ethosomes possess more advantageous transdermal properties and synergistic antipsoriatic efficacy.
研究领域:
药剂学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Kai Dong,Yan Yan,Pengchong Wang,Xianpeng Shi,Lu Zhang,Ke Wang,Jianfeng Xing,Yalin Dong
In this study, a type of multifunctional mixed micelles were prepared by a novel biodegradable amphiphilic polymer (MPEG-SS-2SA) and a multidrug resistance (MDR) reversal agent (d-α-tocopheryl polyethylene glycol succinate, TPGS). The mixed micelles could achieve rapid intracellular drug release and reversal of MDR. First, the amphiphilic polymer, MPEG-SS-2SA, was synthesized through disulfide bonds between poly (ethylene glycol) monomethyl ether (MPEG) and stearic acid (SA). The structure of the obtained polymer was similar to poly (ethylene glycol)-phosphatidylethanolamine (PEG-PE). Then the mixed micelles, MPEG-SS-2SA/TPGS, were prepared by MPEG-SS-2SA and TPGS through the thin film hydration method and loaded paclitaxel (PTX) as the model drug. The in vitro release study revealed that the mixed micelles could rapidly release PTX within 24 h under a reductive environment because of the breaking of disulfide bonds. In cell experiments, the mixed micelles significantly inhibited the activity of mitochondrial respiratory complex II, also reduced the mitochondrial membrane potential, and the content of adenosine triphosphate, thus effectively inhibiting the efflux of PTX from cells. Moreover, in the confocal laser scanning microscopy, cellular uptake and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assays, the MPEG-SS-2SA/TPGS micelles achieved faster release and more uptake of PTX in Michigan Cancer Foundation-7/PTX cells and showed better antitumor effects as compared with the insensitive control. In conclusion, the biodegradable mixed micelles, MPEG-SS-2SA/TPGS, could be potential vehicles for delivering hydrophobic chemotherapeutic drugs in MDR cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料科学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Tingting Song,Hong Wang,Yue Liu,Rongshan Cai,Dezhi Yang,Yongai Xiong
Background Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells. However, the poor solubility and a short half-life of ZgI limit its bioavailability and efficacy. The D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) has been widely used to increase the solubility, improve the encapsulation rate, and extend the half-life of drugs.Methods Here, we formulated the TPGS-modified long-circulating liposomes loading ZgI with a sustained drug release and enhanced therapy for myelosuppression. ZgI-TPGS-liposomes were manufactured using a thin-film hydration technique, followed by characterizations of physicochemical properties, including the particle size, zeta potential, TEM, SEM, FTIR, XRD, stability, drug loading (DL), encapsulation efficiency (EE). The in vitro and in vivo delivery efficiency were further evaluated by cellular uptake, in vitro drug release and in vivo pharmacokinetics. Finally, therapeutic effect on myelosuppression was investigated.Results The ZgI-TPGS-liposomes had an particle size of 97.89 ± 1.42 nm and ZP of −28.65 ± 0.16 mV. It exhibited DL of 9.06 ± 0.76% and EE of 92.34 ± 3.83%, along with excellent storage stability, cellular uptake and sustained drug release to free ZgI and liposomes without TPGS. Additionally, the TPGS modified liposomes significantly enhanced the therapeutic effect of ZgI on CTX induced myelosuppression, which can be confirmed in the apoptosis inhibition and cell viability promotion of CTX injured HSPC-1 cells. Also, the mice in vivo pharmacodynamics demonstrated that TPGS liposomes promoted ZgI increasing the numbers of leucocytes and neutrophils in myelosuppression mice induced by CTX.Conclusion Our research suggest that TPGS-modified long-circulating liposomes loading ziyuglycoside I has potential application in myelosuppression therapy.
研究领域:
药剂学
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药理学
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纳米技术
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中药学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL RESEARCH
·
2018
·Vol. 35
·期 1
·1-15
·
IF 3.335
Jin Ya,Wu Zimei,Li Caibin,Zhou Weisai,Shaw John P.,Baguley Bruce C.,Liu Jianping,Zhang Wenli
Purpose To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration. Methods ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG 2000 ) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers. Stability of micelles was optimized in terms of critical micelle concentration (CMC) and drug release properties. The encapsulation efficiency (EE) and drug loading were determined using an established dialysis-mathematic fitting method. Multicellular spheroids (MCTS) penetration and cytotoxicity were investigated on MCF-7 cell line. Pharmacokinetics of ASL-micelles was evaluated in rats with ASL-solution as control. Results The ASL-micelles prepared with DSPE-PEG 2000 and TPGS (1:1, w /w) exhibited small size (~18.5 nm), higher EE (~94.12%), better sustained in vitro drug release with lower CMC which may be ascribed to the interaction between drug and carriers. Compared to free ASL, ASL-micelles showed better MCTS penetration capacity and more potent cytotoxicity. Pharmacokinetic studies demonstrated that the half-life and AUC values of ASL-micelles were approximately 1.37-fold and 3.49-fold greater than that of free ASL. Conclusions The optimized DSPE-PEG 2000 /TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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生物药剂学
✓ 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）