Frontiers in Pharmacology
·
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
·
炎症研究
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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
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DOI
PubMed
高影响因子
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
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药物代谢动力学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2019
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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
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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
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药物代谢动力学
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肝脏保护研究
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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
·
微生物学
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DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2022
·
IF 3.727
Xinyi Shen,Wanjing Rong,Michael Adu-Frimpong,Qing He,Xiaoxiao Li,Feng Shi,Hao Ji,Elmurat Toreniyazov,Xiaoli Xia,Jian Zhang,Qilong Wang,Jiangnan Yu,Ximing Xu
Purpose To prepare polyethylene glycol succinate-vitamin E modified pinocembrin (PCB)-loaded liposomes (PCBT-liposomes) and evaluate PCBT-liposomal pharmacokinetics and antihyperglycemic activity.Significance The novel PCBT-liposomes demonstrated a promising application prospect as a nano drug carrier for future research.Methods Thin film dispersion was used to prepare PCBT-liposomes. We measured a series of characterization, followed by in vitro cumulative release, in vivo pharmacokinetic study, and antihyperglycemic activity evaluation.Results PCBT-liposomes displayed spherical and bilayered nanoparticles with mean particle size (roughly 92 nm), negative zeta potential (about −26.650 mV), high drug encapsulation efficiency (87.32 ± 1.34%) and good storage (at 4 or 25 °C) stability during 48 h after hydration. The cumulative release rate of PCBT-liposomes was markedly higher than free PCB in four different pH media. In vivo investigation showed that PCBT-liposomes could obviously improve oral bioavailability of PCB by 1.96 times, whereas the Cmax, MRT0–t, and T1/2 of PCBT-liposomes were roughly 1.700 ± 0.139 µg·mL−1, 12.695 ± 1.647 h, and 14.244 h, respectively. In terms of biochemical analysis, aspartate amino-transferase (AST), alanine amino-transferase (ALT), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) concentrations in serum of diabetic mice were respectively decreased 28.28%, 17.23%, 17.77%, and 8.08% after PCBT-liposomal treatment.Conclusion These results show PCBT-liposomal preparation as an excellent nano-carrier which has the potential to improve water solubility, bioavailability, and antihyperglycemic activity of PCB, amid broadening the application of PCB in the clinical settings.
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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糖尿病研究
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DOI
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 35
·25289-25300
·
IF 3.9
Jian-jun Zhang,Qiu-shui Luo,Qing-qing Li,Qian Xu,Xiang Geng,Jian-hua Xiong
Chlorogenic acid (CGA), a polyphenol compound, exhibits excellent anti-oxidative, anti-hypoxic, antibacterial, antiviral, and anti-inflammatory activities, however the bioactivity of it has not been fully utilized in vivo due to its instability and low bioavailability. To address these issues, we prepared and characterized CGA-TPGS-LP, which is a TPGS-modified liposome loaded with CGA. The pharmacokinetics of CGA-TPGS-LP were studied in rats after oral administration. CGA-TPGS-LP was fabricated using a combination of thin film dispersion and ion-driven methods. The liposomes were observed to be uniformly small and spherical in shape. Their membranes were composed of lecithin, cholesterol, and TPGS lipophilic head with a TPGS hydrophilic tail chain coating on its surface. The loading efficiency and encapsulation efficiency were found to be 11.21% and 83.22%, respectively. The physicochemical characterisation demonstrated that the CGA was present in an amorphous form and retained its original structural state within the liposomal formulation. The stability of CGA was significantly improved by fabricating TPGS-LP. CGA-TPGS-LP exhibited good sustained-release properties in both simulated gastric and intestinal fluids. Following oral administration, ten metabolites were identified in rat plasma using UPLC-QTOF-MS. UPLC-QqQ-MS/MS quantitative analysis demonstrated that the oral bioavailability of CGA encapsulated in TPGS-modified liposomes was enhanced by 1.52 times. In addition, the three main metabolites of CGA had higher plasma concentrations and slower degradation rate. These results demonstrate that TPGS-modified liposomes could be a feasible strategy to further enhance the oral bioavailability of CGA, facilitating its clinical use.
研究领域:
药剂学
·
药理学
·
分析化学
·
药物递送系统
✓ 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）