COLLOID AND POLYMER SCIENCE
·
2016
·Vol. 295
·期 1
·259-266
·
IF 1.89
Shi Yanan,Zhu Haibo,Ren Yan,Li Keke,Tian Baocheng,Han Jingtian,Feng Dongxiao
Poly(ethylene glycol)-poly(D,L-lactide) (PEG-PLA), a type of copolymer widely used for drug delivery, was synthesized in the present work based on previous studies, which is used for bovine serum albumin (BSA)-loaded micelle formulation. The micelles exhibited less than 100 nm in size with narrow polydispersity indices (PDI) of smaller than 0.3, and showed an encapsulation efficiency of 69%. BSA was encapsulated in the PEG-PLA micelle successfully exhibiting intact structure indicated by native polyacrylamide gel electrophoresis (Native-PAGE), fluorescence spectroscopy and fourier transform infrared spectroscopy (FTIR) analysis methods. It investigated the effects of freeze-drying, varying amount of cryoprotectants (sucrose, mannitol and lactose), and ultrasonication treatment on the size, and size distribution. The micelles were agglomerated in the freeze-drying process demonstrated by transmission electron microscope (TEM) and dynamic light scattering (DLS) analysis. Five percent of mannitol and ultrasonication for 90 s were found producing a significant reduction in agglomeration as well as a sharp decrease in size. The results demonstrated suitable cryoprotectant, and ultrasonication are beneficial to control the size and distribution of protein-loaded PEG-PLA micelle.
研究领域:
药剂学
·
药物递送
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聚合物科学
·
蛋白质工程
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产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Zhijie Liang,Jinzhuai Li,Hai Huang,Hongmian Jiang,Lifeng Luo,Shaorong Li,Huali Huang,Fangdi Hu
Pancreatic ductal adenocarcinoma (PDAC) poses significant therapeutic challenges due to its unique tumor microenvironment, which is characterized by collapsed blood vessels and elevated intratumoral pressure, severely hindering drug penetration and distribution. Consequently, we synthesized glucose-modified PEG-PLA (polyethylene-polylactice acid) nanoparticles as a drug delivery system for doxorubicin (DOX). We successfully enhanced the permeability and targeting capability of the nanoparticles in pancreatic cancer cells using glycosylation modification, significantly increasing drug accumulation within the tumor microenvironment. Our study demonstrated excellent cellular uptake of the nanoparticles in vitro and their improved penetration in 3D tumor spheroid models. Additionally, in vivo experiments revealed a notable increase in nanoparticle accumulation at the tumor site, along with favorable drug release characteristics. Hence, glucose-modified PEG-PLA nanoparticles hold substantial potential for clinical application in PDAC treatment, effectively enhancing the therapeutic efficacy of chemotherapeutic agents.
研究领域:
药剂学
·
肿瘤学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Xingye Feng,Di Jiang,Ting Kang,Jianhui Yao,Yixian Jing,Tianze Jiang,Jingxian Feng,Qianqian Zhu,Qingxiang Song,Nan Dong,Xiaoling Gao,Jun Chen
The combination of photodynamic therapy (PDT) and chemotherapy holds great potential in combating drug-resistant cancers. However, the major challenge that lies ahead is how to achieve high coloading capacity for both photosensitizer and chemo-drugs and how to gain efficient delivery of drugs to the drug-resistant tumors. In this study, we prepared a nanovehicle for codelivery of photosensitizer (pyropheophorbide-a, PPa) and chemo-drugs (paclitaxel, PTX) based on the synthesis of PPa-conjugated amphiphilic copolymer PPa-PLA-PEG-PLA-PPa. The obtained nanoparticles (PP NP) exhibited a satisfactory high drug-loading capacity for both drugs. To achieve effective tumor-targeting therapy, the surface of PP NP was decorated with a tumor-homing and penetrating peptide F3. In vitro cellular experiments showed that F3-functionalized PP NP (F3-PP NP) exhibited higher cellular association than PP NP and resulted in the strongest antiproliferation effect. In addition, compared with the unmodified nanoparticles, F3-PP NP exhibited a more preferential enrichment at the tumor site. Pharmacodynamics evaluation in vivo demonstrated that a longer survival time was achieved by the tumor-bearing mice treated with PP NP (+laser) than those treated with chemotherapy only or PDT only. Such antitumor efficacy of combination therapy was further improved following the F3 peptide functionalization. Collectively, these results suggested that targeted combination therapy may pave a promising way for the therapy of drug-resistant tumor.
研究领域:
肿瘤学
·
药学
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纳米技术
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Yanan Shi,Wan Huang,Rongcai Liang,Kaoxiang Sun,Fangxi Zhang,Wanhui Liu,Youxin Li
To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO), rhEPO was successfully formulated into poly(ethylene glycol)–poly(d,l-lactide) (PEG–PLA) di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3) and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.
研究领域:
药学
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生物技术
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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
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Qian Wang,Chan Li,Tianyang Ren,Shizhu Chen,Xiaoxia Ye,Hongbo Guo,Haibing He,Yu Zhang,Tian Yin,Xing-Jie Liang,Xing Tang
Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.0%. The nanoparticles were uniform and spherical in shape and exhibited a sustained drug release compared with Taxol. m-NPs also exhibited favorable bioadhesive efficiency at the same time. Coumarin 6 or DiR-loaded nanoparticles with/without PVMMA (C6-m-NPs/DiR-m-NPs or C6-p-NPs/DiR-p-NPs) were used for cellular uptake and intestinal adhesion experiments, respectively. C6-m-NPs were shown to enhance cellular uptake, and caveolae/lipid raft mediated endocytosis was the primary route for the uptake of the nanoparticles. Favorable bioadhesive efficiency led to prolonged retention in the intestine reflected by the fluorescence in isolated intestines ex vivo. In a ligated intestinal loops model, C6-m-NPs showed a clear advantage for transporting NPs across the mucus layer over C6-p-NPs and free C6. The apparent permeability coefficient (Papp) of PTX-m-NPs through Caco-2/HT29 monolayers was 1.3- and 1.6-fold higher than PTX-p-NPs and Taxol, respectively, which was consistent with the AUC0–t of different PTX formulations after oral administration in rats. PTX-m-NPs also exhibited a more effective anticancer efficacy, with an IC50 of 0.2 ± 1.4 μg/mL for A549 cell lines, further demonstrating the advantage of bioadhesive nanoparticles. The bioadhesive nanoparticles m-NPs demonstrated both mucus permeation and epithelial absorption, and thus, this bioadhesive drug delivery system has the potential to improve the bioavailability of drugs that are insoluble in the gastrointestinal environment.
研究领域:
药学
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纳米技术
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药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 8
·2274-2282
·
IF 6.183
Yue Cai,Zhuomin Xu,Qi Shuai,Fangtao Zhu,Jiao Xu,Xin Gao,Xuanrong Sun
Because of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, block copolymer micelles are widely utilized for chemotherapy drug delivery. In order to further improve the anti-tumor ability and reduce unwanted side effects of drugs, tumor-targeting peptides were used to functionalize the surface of polymer micelles so that the micelles can target tumor tissues. Herein, we synthesized a kind of PEG-PLA that is maleimide-terminated and then conjugated with a specific peptide F3 which revealed specific capacity binding to nucleolin that is overexpressed on the surface of many tumor cells. Then, F3 conjugated, paclitaxel loaded nanoparticles (F3-NP-PTX) were prepared as stable micelles that displayed an enhanced accumulation via a peptide-mediated cellular association in human breast cancer cells (MCF-7). Furthermore, F3-NP-PTX showed a prominent anti-tumor efficacy compared with non-targeting nanoparticles (NP-PTX) both in vitro and in vivo, and showed great potential as an efficacious targeting drug delivery system for breast cancer treatment.
研究领域:
药学
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纳米技术
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 5
·1856
·
IF 4.556
Qi Shuai,Yue Cai,Guangkuo Zhao,Xuanrong Sun
On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects of drugs, cell-penetrating peptides have been used to functionalize the surface of polymer micelles endowed with the ability to target tumor tissues. Herein, we first synthesized functional polyethylene glycol-polylactic acid (PEG-PLA) tethered with maleimide at the PEG section of the block polymer, which was further conjugated with a specific peptide, the transactivating transcriptional activator (TAT), with an approved capacity of aiding translocation across the plasma membrane. Then, TAT-conjugated, paclitaxel-loaded nanoparticles were self-assembled into stable nanoparticles with a favorable size of 20 nm, and displayed a significantly increased cytotoxicity, due to their enhanced accumulation via peptide-mediated cellular association in human breast cancer cells (MCF-7)in vitro. But when further usedin vivo, TAT-NP-PTX showed an acceleration of the drug’s plasma clearance rate compared with NP-PTX, and therefore weakened its antitumor activities in the mice model, because of its positive charge, its elimination by the endoplasmic reticulum system more quickly, and its targeting effect on normal cells leading towards being more toxic. So further modification of TAT-NP-PTX to shield TAT peptide’s positive charges may be a hot topic to overcome the present dilemma.Keywords:cell-penetrating peptide;nanoparticles;active tumor targeting;PEG-PLA
研究领域:
药学
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纳米技术
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癌症研究
·
药物递送系统
✓ 已验证
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
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DOI
高影响因子
Coatings
·
2021
·Vol. 11
·期 7
·790
·
IF 2.881
Weichang Ke,Xiang Li,Mengyu Miao,Bing Liu,Xiaoyu Zhang,Tong Liu
Polylactic acid (PLA) film is an alternative filter material for heat-not-burn (HNB) tobacco, but its controllability in cooling performance is limited. In this work, polyethylene glycol (PEG) was introduced to form a polyethylene glycol/polylactic acid (PEG/PLA) film by electrospinning or electrospraying techniques to enhance the cooling performance, due to its lower glass transition and melting temperatures. The PEG/PLA films with typical electrospun or electrosprayed morphologies were successfully fabricated. One typical endothermic peak at approximately 65 °C was clearly observed for the melting PEG phase in the heating process, and the re-crystallization temperature represented by an exothermic peak was effectively lowered to 90–110 °C during the cooling process, indicating that the cooling performance is greatly enhanced by the introduction of the PEG phase. Additionally, the wetting properties and adsorption properties were also intensively studied by characterizing the contact angles, and the as-prepared PEG/PLA films all showed good affinity to water, 1,2-propandiol and triglyceride. Furthermore, the PEG/PLA film with a PLA content of 35 wt.% revealed the largest elasticity modulus of 378.3 ± 68.5 MPa and tensile strength of 10.5 ± 1.1 MPa. The results achieved in this study can guide the development of other filter materials for HNB tobacco application.Keywords:polylactic acid;polyethylene glycol;electrospinning;heat-not-burn tobacco;cooling performance
研究领域:
材料科学
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高分子科学
·
烟草科学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2014
·
IF 7.261
Yang Liu,Yan-Hua Zhu,Cheng-Qiong Mao,Shuang Dou,Song Shen,Zi-Bin Tan,Jun Wang
There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)- b -poly( d , l -lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NP siCDK1 ) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NP siCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer .
研究领域:
肿瘤学
·
分子生物学
·
药学
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纳米技术
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Chen Donglai,Zhang Fuquan,Wang Jinhui,He Hua,Duan Shanzhou,Zhu Rongying,Chen Chang,Yin Lichen,Chen Yongbing
Background: Erlotinib (ELTN)-based targeted therapy as first-line treatment for epidermal growth factor receptor (EGFR)-mutant lung cancers suffers from insufficient selectivity, side effects, and drug resistance, which poses critical challenges in the clinical setting. Acquired resistance of ELTN results in extremely poor prognoses of non-small cell lung cancer (NSCLC) patients, wherein activation of the JAK2/STAT3 signaling pathway has been proven to induce acquired ELTN resistance.Methods: In this study, we developed a nanoparticle (NP) delivery system based on Food and Drug Administration (FDA)-approved poly(ethylene glycol) (PEG)-poly(lactic acid) (PLA) for the co-delivery of ELTN and fedratinib (FDTN, a small-molecular, highly selective JAK2 inhibitor). Both ELTN and FDTN could be encapsulated into the PEG-PLA NPs via optimization of the encapsulation method. The effect of NPs on NSCLC cells was evaluated by MTT assay. Western blotting was performed to study the molecular mechanisms of NPs inhibiting the downstream pathways of EGFR in vitro. The histological analysis and protein expression in vivo were assessed by hematoxylin/eosin (H&E) staining and immunohistochemistry, respectively.Results: The drug cargoes exhibited great stability, and could be released more efficiently in the acidic tumorous condition. Mechanistic study showed that FDTN notably down-regulated the expression levels of proteins in the JAK2/STAT3 signaling pathway, including p-EGFR, p-JAK2, p-STAT3 and Survivin, therefore reversing the ELTN resistance. As a result, synergistic anti-cancer effect was achieved by PEG-PLA NPs encapsulating both ELTN and FDTN in ELTN-resistant NSCLC tumors both in vitro and in vivo, and lower systemic side effect was noted for the co-delivery NPs compared to free drugs.Conclusion: This study provides a promising approach to overcome the ELTN resistance in the treatment of NSCLC, and the use of FDA-approved materials with clinically applied/investigated chemical drugs may facilitate the translation of the current delivery system.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
分子生物学
·
癌症研究
✓ 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）