JOURNAL OF THE CHINESE CHEMICAL SOCIETY
·
2020
·Vol. 67
·期 5
·874-879
·
IF 1.554
Wenjie Li,Yan Lu,Yi Cheng,Hui Luo,Zhenbin Jia,Ning Li
Curcumol (Cur), which is the primary active anti-liver cancer component of Chinese traditional medicine Rhizoma zedoariae , was encapsulated in galactosylated liposomes to enhance its liver-targeting efficacy. In this study, we optimized the preparation methods, prescription, and process of galactosylated curcumol liposomes (Gal-Cur-L). The experimental results showed that the encapsulation efficiency, particle diameter, and stability coefficient of Gal-Cur-L obtained by the two-step emulsification method were improved compared with those of it obtained by other methods. Single-factor investigation showed that two factors, pH and the amount of triolein, contribute at least partly to the encapsulation efficiency and particle diameter of Gal-Cur-L. The best prescription and process were obtained through orthogonal test: the ratio of lecithin to cholesterol was 2:1, the ratio of drug to lipid was 1:2, and the amount of ether and Twain-80 were 4 ml and 1.6 g/L, respectively, 15 min for ultrasonic time, 100 W for ultrasonic power, and 20 min for homogeneous time. Using the best method, prescription, and process mentioned earlier, the basic test results of Gal-Cur-L were obtained, which demonstrated that our methods, prescription, and process of Gal-Cur-L were applicable. The encouraging results of this study provided references for the research of liver-targeting reagents of curcumol.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2017
·
IF 5.605
Wenping Wang,Yaya Lei,Hong Sui,Wenping Zhang,Rongyue Zhu,Jun Feng,Hong Wang
The aim of the present study was to prepare and evaluate microparticle formulation encapsulated with glycyrrhetinic acid (GA) based on bovine serum albumin (BSA). The drug-loaded nanoparticles were firstly formed by a simple desolvation method, and were further assembled into microparticles using zinc chloride and glutaraldehyde as crosslinkers. The obtained microparticles contained approximately 30% (w/w) drug and showed as spherical particles with a size of about 2 μm. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that GA lost its crystallinity during the nano/microencapsulation process. In vitro dissolution study demonstrated a typical sustained-release pattern for 24 h with a burst of 28.1% at the first 30 min, which fitted well by Higuchi model. After intravenous administration into mice, the microparticle formulation remained a higher drug level than the solution formulation in blood and liver for more than 18 h. These results suggested the potential benefit of using the prepared albumin microparticles as a promising vector for enhanced liver delivery of poorly water-soluble drug.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2014
·Vol. 32
·期 5
·540-550
·
IF 1.42
Guo Hua,Yang Cheng-ling,Wang Wei,Wu Yu-kun,Lai Quan-yong,Yuan Zhi
A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid (GA) and doxorubicin (DOX) conjugates at different ratios. GA (a liver-targeting ligand) and DOX (an antitumor drug) were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate (ALG-mOEG) for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo . In addition, nanoparticles with a 1:1 ( W : W ) ratio of GA-ALG-mOEG and DOXALG-mOEG (NPs-3) showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and antitumor activity in vivo . Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC 0-∞ and t
1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth (88.37% reduction in tumor weight) 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Sichen Li,Difei Zhang,Yi Li,Jingjing Zhou,Jinghua Chen,Yan Zhang
Cisplatin (CDDP) as a first-line chemotherapy drug has long suffered drawbacks of severe side effects and poor pharmacokinetics. Thus, various nano-carriers of complex architectures and multi-step modifications have been developed to overcome these challenges, but a simple delivery system with integrated multi-functions is still in demand. Herein, we synthesized a new type of glyco-based triple hydrophilic block copolymers for the delivery of CDDP and thereof cancer therapy. The incorporated glucuronic acid part is complexed with CDDP with high entrapment efficiency, while providing pH-responsive release in the acidic tumor microenvironment. The galactose segment is implanted for liver-targeting effect, which can also significantly lower the side effects of CDDP. As a result, the CDDP-loaded nanoparticle PGG2/Pt showed selectively faster endocytosis rates into HepG2 cells in vitro, with the calculated IC 50 value even comparable to that of free CDDP. The in vivo experiments on a HepG2-bearing mouse model, PGG2/Pt showed excellent anti-tumor activity and enhanced drug accumulation on tumor, together with much lowered nephrotoxicity, hepatotoxicity, and splenic toxicity. This work provides a new strategy for CDDP delivery with higher loading efficiency as well as biosafety.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY AND PHYSICS OF LIPIDS
·
2023
·
IF 3.4
Jie Hu,Yongsheng Zheng,Zhijie Wen,Hudie Fu,Xuedan Yang,Xuexin Ye,Shengpeng Zhu,Li Kang,Xiaojun Li,Xinzhou Yang,Yan Hu
The aim of this study was to construct a bifunctional liposome with hepatic-targeting capacity by modifying with a targeting ligand and an intracellular tumor reduction response functional group to deliver drugs precisely to focal liver tissues and release them in large quantities in hepatocellular carcinoma cells. This could improve drug efficacy and reduce toxic side effects at the same time. First, the bifunctional ligand for liposome was successfully obtained by chemically synthesizing it from the hepatic-targeting glycyrrhetinic acid (GA) molecule, cystamine , and the membrane component cholesterol. Then the ligand was used to modify the liposomes. The particle size, PDI and zeta potential of the liposomes were determined with a nanoparticle sizer, and the morphology was observed by transmission electron microscopy . The encapsulation efficiency and drug release behavior were also determined. Further, the stability in vitro of the liposomes and the changes in the simulated reducing environment were determined. Finally, the antitumor activity in vitro and cellular uptake efficiency of the drug-loaded liposomes were investigated by performing cellular assays. The results showed that the prepared liposomes had a uniform particle size of 143.6 ± 2.86 nm with good stability and an encapsulation rate of 84.3 ± 2.1 %. Moreover, the particle size of the liposomes significantly increased and the structure was destroyed in a DTT reducing environment. Cellular experiments showed that the modified liposoes had better cytotoxic effects on hepatocarcinoma cells than both normal liposomes and free drugs. This study has great potential for tumor therapy and provides novel ideas for the clinical use of oncology drugs in dosage forms.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Jian Cui,Zhiwei Wen,Huajie Huang,Shuilin Qin,Yanjie Luo,Wei Zhang,Wei Wu
The disadvantage of a traditional dosage regimen is the inability to deliver a sufficient drug concentration to the lesion site, which can result in adverse side effects due to nonspecific drug delivery. Actively targeting hepatic cells is a promising therapeutic strategy for liver disease. In this study, l-carnitine and a targeting peptide derived from the hepatitis B virus large envelope protein were used to modify liposomes for drug delivery to the liver through the sodium taurocholate cotransporting polypeptide (NTCP) and the organic cation/carnitine transporter 2 (OCTN2) receptors. Silybin was selected as the model drug. The solubility of silybin can reach 0.3 mg/mL after encapsulation in liposomes. The NTCP-specific and OCTN2-accelerated Myrcludex B and l-carnitine dual-modified liposomes were validated in vitro. The uptake of coumarin-6 in dual ligand-modified liposomes by hepatocytes was up to 2.36 μg/mg compared with unmodified liposomes (1.05 μg/mg). The pharmacokinetics and targeting abilities of various liposome formulations were evaluated in Kunming mice. Targeted liposomes increased the concentration of silybin and prolonged the drug’s retention time in the liver. The area under the liver’s pharmacokinetic curve of targeted liposomes was twice that of silybin injection, suggesting the promising application potential of silybin-loaded hepatotropic nanovesicles.
研究领域:
药理学
·
药物递送系统
·
肝脏疾病治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Methods
·
2025
·
IF 9.1
Xinlong Liu,Yimeng Li,Xinhua Liu,Yangyang Huang,Fujun Wang,Jiafeng Li,Yuqi Guo,Xinyuan Zhu,Lijuan Zhu,Chuan Zhang
Plasmids are widely used gene vectors in gene therapy, yet their efficient delivery remains a major challenge for achieving optimal therapeutic outcomes. Recently, poly(β-amino esters) (PBAEs) have emerged as promising carriers for non-viral gene delivery due to their tunable structures and high delivery efficiency. Nonetheless, the cationic nature of PBAEs raises toxicity concerns, and their lack of tissue-specific targeting capability limits their clinical application. Herein, a novel PBAE for efficient plasmid delivery is constructed, which contains disulfide bonds in the backbone and N-acetylgalactosamine (GalNAc) moieties at the terminals (GalNAc-PBAEs). To address the potential reduction in nucleic acid condensing capacity caused by end-capping PBAE with GalNAc, the commonly used end-capping amines in conventional PBAE are employed as monomers to create GalNAc-PBAEs with tertiary amine side chains. Through side-chain screening, the optimized GalNAc-PBAE exhibits enhanced transfection efficiency, surpassing that of the conventional top-performing PBAE, C28-E7, and rivaling the commercial transfection reagent Lipo2000. Importantly, the GalNAc moieties enable the plasmid-PBAE polyplex to efficiently target the liver. In a mouse model with acute liver fibrosis, the efficient delivery and expression of a representative plasmid encoding HGF significantly mitigate liver fibrosis and improve liver function, demonstrating the potential of the designed PBAE in gene therapy.
研究领域:
生物医学工程
·
基因治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Siyu Sun,Xiyou Du,Manfei Fu,Abdur Rauf Khan,Jianbo Ji,Weidong Liu,Guangxi Zhai
In this study, galactosamine-modified poly(ethylene glycol)-poly(lactide) (Gal-PEG-PLA) polymers were synthesized and Gal-PEG-PLA/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles named as GPP micelles were designed to promote the oral absorption of a hydrophobic drug, curcumin (CUR). CUR-loaded Gal-PEG-PLA/TPGS micelles (CUR@GPP micelles) were fabricated using the thin-film dispersion method. CUR@GPP micelles had a size of about 100 nm, a near-neutral zeta potential , drug loading (DL) of 14.6%, and sustained release properties. GPP micelles with high Gal density (GPP3 micelles) were superior in facilitating uptake in epithelial cells and improving intestinal permeation. In situ intestinal absorption studies suggested that the jejunum and ileum were the best absorption segments in the intestinal tract. Additionally, biodistribution results revealed that GPP3 micelles could be remarkably taken up by the jejunum and ileum. Pharmacokinetics revealed that the maximum plasma concentration (C max ) and the area under the plasma concentration-time curve from 0 to 24 h (AUC 0–24 ) for CUR@GPP3 micelles were both significantly increased, and that the relative bioavailability of CUR@GPP3 micelles to CUR-loaded mPEG-PLA/TPGS micelles (CUR@PP micelles) was 258.8%. Furthermore, CUR-loaded micelles could reduce damage to the liver and intestinal tissues. This study highlights the importance of Gal content in the design of targeting nanocarrier Gal-modified micelles, which have broad prospects for oral delivery of hydrophobic drugs. Therefore, they could serve as a promising candidate for targeted delivery to the liver.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2021
·Vol. 17
·期 12
·2455-2465
·
IF 4.099
Chen Jing,Lin Yuan,Wu Min,Li Chuangnan,Zhang Yimin,Chen Dongpeng,Cheng Yi
This research was performed to optimize the enzymatic synthesis of mannosylated ligand with which to prepare mannosy-lated liposomes and investigate their bioactivity. Based on single-factor studies, lipase dose, substrate molar ratio (diester lauric diacid-cholesterol to mannose) and
temperature were identified as significant parameters, and optimal reaction conditions were determined through response surface methodology (RSM) with central composite design. The optimum operating parameters, 61.23 mg of lipase, a substrate molar ratio of 5.36, and 56.64 °C temperature
offered a predicted yield (71.11%) which was consistent with the actual yield (69.08%). Drug-free mannosylated liposomes were prepared film-dispersion. The characterizations of these liposomes showed that mannosylated liposomes were well-dispersible spherical particles with an average particle
size of 142.3 nm, the polydispersity index of 0.16, and a zeta potential of −19.8 mV. Pyrogen examination, hemolytic studies and cytotoxicity assays revealed no substantial safety concern for drug-free mannosylated liposomes. Cellular uptake efficiency of mannosylated liposomes by HepG2
cells was significantly higher than that of unmodified liposomes, demonstrating that mannosylated ligands have a positive effect on liver targeting. Overall, mannosylated liposomes could be active drug delivery system for combatting the therapy of hepatic diseases.
研究领域:
药剂学
·
生物医学工程
·
肝脏疾病治疗
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Ting Zhou,Xin Tang,Wei Zhang,Jianfang Feng,Wei Wu
10-Hydroxycamptothecin (HCPT) liposomes surface modified with stearyl glycyrrhetinate (SG) were prepared by the film dispersion method. Characterization of the liposomes, including drug release in vitro, pharmacokinetics and tissue distribution, was done. HCPT in plasma and tissues was determined by high-performance liquid chromatography (HPLC). Compared with the conventional HCPT-liposomes and commercially available hydroxycamptothecin injection (HCPT Inject), pharmacokinetic parameters indicated that SG-HCPT-liposomes had better bioavailability. Regarding tissue distribution, the concentration of HCPT loaded by SG modified liposomes in the liver was higher than other tissues and the risk to the kidney was lower than HCPT-liposomes and HCPT Inject. These results support the hypothesis that the HCPT-liposomes modified with SG show enhanced liver-targeting through the glycyrrhetinic acid (GA) receptor to be an efficient drug carrier, which may help to improve therapeutic methods for hepatic diseases in the future.
研究领域:
药剂学
·
生物医学
✓ 已验证
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Menghua Gao,Jiafeng Zhong,Xinxin Liu,Yanjun Zhao,Dingcheng Zhu,Xiaohuo Shi,Xuehan Xu,Qin Zhou,Wenjing Xuan,Yue Zhang,Yaofeng Zhou,Jianjun Cheng
Organ- and cell-specific delivery of mRNA via modular lipid nanoparticles (LNPs) is promising in treating various diseases, but targeted cargo delivery is still very challenging. Most previous work focuses on screening ionizable and helper lipids to address the above issues. Here, we report the multifacial role of PEGylated lipids in manipulating LNP-mediated delivery of mRNA to the liver. We employed the typical excipients in LNP products, including DLin-MC3-DMA, DPSC, and cholesterol. Five types of PEGylated lipids were selected, and their molar ratio was fixed at 1.5% with a constant PEG molecular weight of 2000 Da. The architecture of steric lipids dramatically affected the in vitro gene transfection, in vivo blood clearance, liver deposition, and targeting of specific cells, all of which were closely linked to the de-PEGylation rate. The fast de-PEGylation resulted in short blood circulation and high accumulation in the liver. However, the ultrafast de-PEGylation enabled the deposition of more LNPs in Kupffer cells other than hepatocytes. Surprisingly, simply changing the terminal groups of PEGylated lipids from methoxyl to carboxyl or amine could dramatically increase the liver delivery of LNPs, which might be associated with the accelerated de-PEGylation rate and enhanced LNP–cell interaction. The current work highlights the importance of manipulating steric lipids in promoting mRNA delivery, offering an alternative approach for formulating and optimizing mRNA LNPs.
研究领域:
分子生物学
·
药物递送
·
生物医学工程
✓ 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）