查找使用阿拉丁产品的科研文献

Paclitaxel-loaded and folic acid-modified PLGA nanomedicine with glutathione response for the treatment of lung cancer

Yao Wang,Yao Jialiang,Qian Fangfang,Que Zujun,Yu Pan,Luo Tianle,Zheng Dan,Zhang Zhanxia,Tian Jianhui

Targeted delivery and smart response of nanomedicine hold great promise for improving the therapeutic efficacy and alleviating the side effects of chemotherapy agents in cancer treatment. However, availability of only a few studies that discuss organic nanomedicines with these properties limits the development prospects of nanomedicines. In the present study, folic acid (FA)-targeted delivery and glutathione (GSH) smart responsive nanomedicine were rationally designed for paclitaxel (PTX) delivery for the treatment of lung cancer. Compared with other stimuli-responsive nanomedicines, this nanocarrier was not only sensitive to biologically relevant GSH for on-demand drug release but also biodegradable into biocompatible products after fulfilling its delivery task. The nanomedicine first entered tumor cells via FA and its receptor-mediated endocytosis. After the lysosomal escape, poly(lactic-co-glycolic acid) (PLGA) nanomedicine was triggered by a higher level of GSH and released its cargo into the tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells significantly but also possessed less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the potential of a multifunctional nano-platform to enhance bioavailability and reduce the side effects of chemotherapy agents.

Paclitaxel-loaded lignin particle encapsulated into electrospun PVA/PVP composite nanofiber for effective cervical cancer cell inhibition

Baoe Li,Xiaomei Xia,Jiatian Chen,Dan Xia,Ruodan Xu,Xianrui Zou,Hongshui Wang,Chunyong Liang

Electrospun composite nanofibrous scaffolds have been regarded as a potential carrier for local drug delivery to prevent tumor recurrence. Herein, a model drug (paclitaxel) was creatively loaded into lignin nanoparticles (PLNPs) and then encapsulated into the polymer of poly (vinyl alcohol)/polyvinyl pyrrolidone which has been fabricated into a composite nanofibrous membrane (PVA/PVP-PLNPs) for use as a drug carrier using the electrospinning technique. The fabricated PVA/PVP-PLNPs membranes exhibited good particle distribution, mechanical properties, thermal stability and biocompatibility. In vitro experiments showed that combining lignin nanoparticles by electrospinning not only improved the drug release profile, but also enhanced the hydrophilicity of nanofibrous membranes which was beneficial to cell adhesion and proliferation. Cellular experiments demonstrated that PVA/PVP-2%PLNPs membrane showed good cell inhibition ability, and the cell survival rate was only 21% at day 7. It indicates that the as-prepared PVA/PVP-PLNPs composite nanofibers are promising candidates for local anticancer therapy.

Multi-functional chitosan polymeric micelles as oral paclitaxel delivery systems for enhanced bioavailability and anti-tumor efficacy

Tian'e Chen,Liangxing Tu,Ge Wang,Na Qi,Wei Wu,Wei Zhang,Jianfang Feng

Chitosan is widely used as a permeation enhancer for oral drug delivery, although its drawbacks include a limited enhancement of drug bioavailability and an inability to form micelles. In this study, we designed a novel chitosan derivative (GA-CS-TPGS copolymer) and constructed paclitaxel micelles (PTX-Micelles) designed to have multiple functions associated with the GA-CS-TPGS copolymer (enhanced bioadhesion, inhibited P-gp efflux and drug metabolism in liver) and the micelles (enhanced solubility and permeability) to enhance the bioavailability and anti-tumor efficacy of PTX. The results showed that the PTX-Micelles system could alter the in vivo pharmacokinetic performance and therapeutic effect of PTX via its predesigned functions. The bioavailability of PTX was enhanced approximately 3.80-fold by the PTX-Micelles, and an enhanced anti-lung tumor efficacy of PTX-Micelles was observed when compared to Taxol®. The results of this study indicate that constructing micelles with a multifunctional chitosan derivative may be a promising approach to enhance the oral bioavailability and anti-tumor efficacy of poorly soluble drugs.

Paclitaxel-loaded dextran nanoparticles decorated with RVG29 peptide for targeted chemotherapy of glioma: an in vivo study

Hailing Han,Ying Zhang,Shunzi Jin,Ping Chen,Shi Liu,Zhigang Xie,Xiabin Jing,Zhanfeng Wang

Gliomas are the most common malignant brain tumors and notorious due to the blood–brain barrier (BBB). In this study, an RVG peptide is used as a targeting ligand to construct multi-targeting micelles (RVG–Dex–PTX) towards the brain (passing the BBB) and brain glioma. In vivo imaging and fluorescence imaging were carried out. The results showed that Cy5-labeled M(RVG, PTX) can cross the BBB and reach the intracranial C6 glioma, prolonging the median mean survival time. Specifically, the elevated RVG29 could enhance the uptake of the micelles by C6 glioma cells and thus enhance the PTX efficacy. In conclusion, RVG29 is a promising targeting peptide for the BBB and intracranial tumors, and the M(RVG, PTX) micelles prepared from dextran, PTX, and RVG29 are a potential formulation for C6 glioma treatment.

TMTP1-Modified, Tumor Microenvironment Responsive Nanoparticles Co-Deliver Cisplatin and Paclitaxel Prodrugs for Effective Cervical Cancer Therapy

Guiying Jiang,Xueqian Wang,Ying Zhou,Chenming Zou,Ling Wang,Wei Wang,Danya Zhang,Hanjie Xu,Jie Li,Fei Li,Danfeng Luo,Xiangyi Ma,Ding Ma,Songwei Tan,Rui Wei,Ling Xi

Cysteine modified and bile salt based micelles: Preparation and application as an oral delivery system for paclitaxel

Wei Xu,Xiaohui Fan,Yanli Zhao,Lingbing Li

The aim of the present study is to construct a cysteine modified polyion complex micelles made of Pluronic F127-chitosan (PF127-CS), Pluronic F127-cysteine (PF127-cysteine) and sodium cholate (NaC) and to evaluate the potential of the micelles as an oral drug delivery system for paclitaxel. Systematic studies on physicochemical properties including size distribution, zeta-potential and morphology were conducted to validate the formation of micelle structure. Compared with Pluronic micelles, drug-loading capacity of PF127-CS/PF127-cysteine/NaC micelles was increased from 3.35% to 12.77%. Both the critical micelle concentration and the stability test confirmed that the PF127-CS/PF127-cysteine/NaC micelles were more stable in aqueous solution than sodium cholate micelles. Pharmacokinetic study demonstrated that when oral administration the area under the plasma concentration–time curve (AUC 0–∞ ) and the absolute bioavailability of paclitaxel-loaded micelles were five times greater than that of the paclitaxel solution. In general, PF127-CS/PF127-cysteine/NaC micelles were proven to be a potential oral drug delivery system for paclitaxel.

Amphiphilic nanoparticles based on poly(vinyl pyrrolidone) and stearoyl modified chitosan as drug vehicles for paclitaxel delivery

Zhao Liu,Teng Zhang,Cui Tang,Chunhua Yin

Poly(vinyl pyrrolidone) (PVP) and stearoyl chloride (SC) double-grafted chitosan (PCS) nanoparticles (NPs) were prepared for paclitaxel (PTX) delivery. PTX could be effectively loaded into PCS NPs with encapsulation efficiency of 92.8%. PTX-loaded PCS NPs (PTX/PCS NPs), which possessed particle sizes of 144   nm and Zeta potentials of −7.5   mV, exhibited a sustained release behavior. In H-22 tumor bearing mice, significantly enhanced antitumor efficacies were achieved by PTX/PCS NPs with the tumor inhibition ratio (TIR) of 76.1% as compared with PTX injection. Furthermore, no signs of sub-acute toxicity were detected in healthy mice, indicating the safety of PCS NPs. Therefore, PCS NPs could be served as an effective and safe carrier for PTX delivery.

l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells

Shiwei Niu,David H. Bremner,Junzi Wu,Jianrong Wu,Haijun Wang,Heyu Li,Qianqian Qian,Hong Zheng,Limin Zhu

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid – and thermally activated – PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

Folate-conjugated and pH-triggered doxorubicin and paclitaxel co-delivery micellar system for targeted anticancer drug delivery

Lijing Niu,Feiyan Zhu,Bowen Li,Lingling Zhao,Hongze Liang,Yinghua Yan,Hui Tan

A folate-conjugated and pH-sensitive polymeric micellar system for the co-delivery of DOX and PTX was studied. A doxorubicin conjugated prodrug was synthesized via Schiff's base reaction. Subsequently, folate was grafted onto the prodrug and PTX was encapsulated. Sustained drug release of both DOX and PTX from the polymeric micelles was observed and the release rate could be accelerated by decreasing the media pH. A cellular uptake assay revealed that the polymeric micelles were internalized in the cytoplasm via endocytosis by SW1353 cells, and the cellular uptake was enhanced for the folate-conjugated micelles due to an active FR-mediated endocytosis pathway, showing stronger red fluorescence compared to that of non-folate micelles. The in vitro anticancer efficiency of the polymeric micellar system was evaluated using a cytotoxicity assay by incubating different drug formulations with the SW1353 cells. Both free drugs and micellar formulations displayed inhibition of cell growth at different levels, while the folate-conjugated dual-drug loaded polymeric micelles (Folate–Oxd–DOX/PTX) displayed a much lower IC50 value than other drug formulations, indicating a desirable in vitro anticancer efficiency due to the synergistic effect of co-delivery and active targeting. Thus, the polymeric micellar system is a promising platform for targeted cancer chemotherapy.

Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid

Lingfei Han,Lejian Hu,Fulei Liu,Xin Wang,Xiaoxian Huang,Bowen Liu,Feng Feng,Wenyuan Liu,Wei Qu

The application of paclitaxel (PTX) in clinic has been restricted due to its poor solubility. Several traditional nano-medicines have been developed to improve this defect, while they are still lack of tumor targeting ability and rapid drug release. In this work, an amphiphilic polymeric micelle of hyaluronic acid (HA) – all-trans-retinoid acid (ATRA) with a disulfide bond, was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with self-assembling to micelles in water, the delivery system displayed satisfying drug loading capacities for both PTX (32.62% ± 1.39%) and ATRA, due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles (HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides, HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16F10 cells. Due to these properties, cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly, HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore, redox-sensitive HA-SS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.

Amphiphilic Polymeric Micelles Based on Deoxycholic Acid and Folic Acid Modified Chitosan for the Delivery of Paclitaxel

Liang Li,Na Liang,Danfeng Wang,Pengfei Yan,Yoshiaki Kawashima,Fude Cui,Shaoping Sun

The present investigation aimed to develop a tumor-targeting drug delivery system for paclitaxel (PTX). The hydrophobic deoxycholic acid (DA) and active targeting ligand folic acid (FA) were used to modify water-soluble chitosan (CS). As an amphiphilic polymer, the conjugate FA-CS-DA was synthesized and characterized by Proton nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared spectroscopy (FTIR) analysis. The degree of substitutions of DA and FA were calculated as 15.8% and 8.0%, respectively. In aqueous medium, the conjugate could self-assemble into micelles with the critical micelle concentration of 6.6 × 10−3mg/mL. Under a transmission electron microscope (TEM), the PTX-loaded micelles exhibited a spherical shape. The particle size determined by dynamic light scattering was 126 nm, and the zeta potential was +19.3 mV. The drug loading efficiency and entrapment efficiency were 9.1% and 81.2%, respectively. X-Ray Diffraction (XRD) analysis showed that the PTX was encapsulated in the micelles in a molecular or amorphous state. In vitro and in vivo antitumor evaluations demonstrated the excellent antitumor activity of PTX-loaded micelles. It was suggested that FA-CS-DA was a safe and effective carrier for the intravenous delivery of paclitaxel.Keywords:chitosan;deoxycholic acid;folic acid;amphiphilic polymer;micelles;paclitaxel

Development of a Thermally Responsive Nanogel Based on Chitosan–Poly(N-Isopropylacrylamide-co-Acrylamide) for Paclitaxel Delivery

Yajing Wang,Hongjiang Xu,Jiu Wang,Liang Ge,Jiabi Zhu

ABSTRACT A thermally responsive nanogel was developed through the radical polymerization based on chitosan (CTS) and N-isopropylacrylamide (NIPAAm) with acrylamide (AAm) blended to explore the possibility of increasing the volume phase transition temperature (VPTT). The thermally sensitive features of resultant nanogels were studied by determining variance of transmittance and changeable size. The VPTT of the CTS–poly(NIPAAm-co-AAm5.5) nanogel, coplymerized with 5.5% wt. AAm /wt. NIPAAm, was 38°C in contrast to 32°C of the CTS–poly(NIPAAm) polymer and the former was studied thereafter. The critical aggregation concentration of CTS–poly(NIPAAm-co-AAm5.5) nanogels was 1.11 μg/mL, much smaller than CTS–poly(NIPAAm) nanogels (5.00 μg/mL). Paclitaxel (PTX) was encapsulated in CTS–poly(NIPAAm-co-AAm5.5) nanogels with loading efficiency of about 9.06 ± 0.195% ( n = 3). Thermally responsive PTX in vitro release fromPTX-loaded nanogels was verified. Coumarin-6-loaded nanogels showed thermally responsive cellular uptake because of electrostatic absorptive endocytosis. Furthermore, the half maximal inhibitory concentration of PTX-loaded nanogels was about 2.025 nmol/L, 10-fold improved relative to PTX solutions against SMMC 7721 cells. In vivo , PTX-loaded nanogels presented remarkably higher antitumor efficacy against human colon carcinoma cells HT-29 xenograft nude mice model after intravenous administration. Accordingly, our results reinforced the potential means of CTS–poly(NIPAA m -co-AAm5.5) nanogels for the combination of thermal therapy and chemotherapy.