JOURNAL OF BIOMATERIALS APPLICATIONS
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2020
·
IF 2.22
Jiyang Liu,Na Liang,Shupeng Li,Yang Han,Pengfei Yan,Yoshiaki Kawashima,Fude Cui,Shaoping Sun
The clinical application of paclitaxel is limited due to its low solubility and severe side effects. A tumor-targeting and redox-sensitive paclitaxel-loaded micellar system could exhibit high drug solubility, excellent antitumor activity and low toxicity to normal tissues. An mPEG and hexadecanol-modified hyaluronic acid with disulfide bridges in the molecules (mPEG-S-S-HA-C16) was designed and synthesized. Using mPEG-S-S-HA-C16 as the carrier, the paclitaxel-loaded micelles were fabricated, and their physicochemical properties were studied deeply. Moreover, the antitumor evaluation of the paclitaxel-loaded micelles was conducted in vitro and in vivo. For the optimized paclitaxel-loaded mPEG-S-S-HA-C16 micelles, the average size and zeta potential were 168.6 nm and −38.2 mV, respectively. In vitro drug release study demonstrated the redox-sensitivity of the micelles that the encapsulated paclitaxel could be released rapidly in the presence of glutathione. MTT assay confirmed the low toxicity of the polymeric material itself and the excellent cytotoxicity of paclitaxel-loaded mPEG-S-S-HA-C16 micelles against MCF-7 cells. Moreover, the in vivo antitumor evaluation demonstrated the superior antitumor efficacy of the paclitaxel-loaded micelles. These results suggested that the paclitaxel-loaded mPEG-S-S-HA-C16 micelles held great promise for targeted delivery of paclitaxel.
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RSC Advances
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2021
·Vol. 11
·期 21
·12757-12770
·
IF 3.361
Man Li,Longbing Ling,Qing Xia,Xinsong Li
Micelles self-assembled from small amphiphilic molecules are unstable in biological fluids, and thus are poor drug carriers. In contrast, amphiphilic polymer micelles can encapsulate hydrophobic drugs in their core to greatly enhance their aqueous solubility and extend their retention time in blood circulation owing to their hydrophilic shell. However, the major disadvantages of conventional polymer micelles are the heterogeneity of the amphiphilic polymer structure and premature drug leakage. Thus, herein, to address these shortcomings, disulfide crosslinked micelles composed of a small amphiphilic molecule, di-lipoyl-glycerophosphorylcholine (di-LA-PC), were developed as redox-responsive drug carriers. Specifically, di-LA-PC was synthesized and self-assembled to form crosslinked micelles under catalysis by dithiothreitol. The disulfide crosslinked micelles maintained high stability in a simulated physiological environment, but rapidly disassembled under reductive conditions. Furthermore, paclitaxel (PTX), as a model drug, was encapsulated in the core of the crosslinked micelles with a high loading content of 8.13%. The in vitro release studies indicated that over 80% of PTX was released from the micelles in the reductive environment, whereas less than 20% PTX was released without reduction in the 68 h test. Benefiting from their nanoscale characteristics, the PTX-loaded micelles showed efficient cellular internalization and effectively induced the death of cancer cells, as revealed in the MTT, apoptosis and cell cycle tests. Moreover, pharmacokinetic studies demonstrated that the crosslinked micelles prolonged the circulation of the incorporated PTX in the bloodstream and increased its accumulation in the tumor tissue via the EPR effect. Finally, the PTX-loaded micelles displayed prominent in vivo anti-tumor activity in a 4T1 xenograft tumor model. In summary, the di-LA-PC crosslinked micelle platform possesses excellent stability, high loading capacity and reduction-responsive release profile, which may have applications in the delivery of PTX and other anti-cancer drugs.
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CHEMICAL ENGINEERING JOURNAL
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2017
·
IF 6.216
Ming Zhang,Jing Wang,Wentao Wang,Jun Zhang,Ninglin Zhou
Carbon dots could be extended in biological applications for drug delivery and photothermal therapeutics due to their ability to improving therapeutic effect and reducing side effects. Here, we use doxorubicin (DOX) as the model drug, the amino and carboxyl coated magnetofluorescent carbon quantum dots (GdN@CQDs) as a carrier, Genipin (GP) as cross-linking agent to design and prepare a multifunctional drug delivery system triggered by near-infrared (NIR) light and pH dual-stimuli. The cytotoxicity of the nanoparticles has been examined by MTT assay. The fluorescent GdN@CQDs/GP serves as both a controllable drug release gatekeeper and a fluorescent probe for the visualization of the drug delivery process. In vitro and in vivo experiments showed that this platform can deliver anti-cancer drugs to cells, releasing them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photothermal synergistic therapeutic effect.
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MACROMOLECULAR BIOSCIENCE
·
2018
·Vol. 18
·期 3
·1700339
·
IF 3.392
Xuelin Wang,Juanjuan Li,Qi Yan,Yanrui Chen,Aiping Fan,Zheng Wang,Yanjun Zhao
Redox-responsive micelles are versatile nanoplatforms for on-demand drug delivery, but the in situ evaluation of drug release is challenging. Fluorescence resonance energy transfer (FRET) technique shows potential for addressing this, while the aggregation-caused quenching effect limits the assay sensitivity. The aim of the current work is to combine aggregation-induced emission (AIE) probe with FRET to realize drug release assessment from micelles. Tetraphenylethene (TPE) is selected as AIE dye and curcumin (Cur) is chosen as the model drug as well as FRET receptor. The drug is covalently linked to a block copolymer via the disulfide bond linker and TPE is also chemically linked to the polymer via an amide bond; the obtained amphiphilic polymer conjugate self-assembles into micelles with a hydrodynamic size of ≈125 nm. Upon the supplement of glutathione or tris(2-carboxyethyl)phosphine) trigger (10 × 10 −3 m ), the drug release induces the fluorescence increase of both TPE and Cur. Accompanied with the FRET decay, absorption enhancement and particle size increase are observed. The same phenomenon is observed in MCF-7 cells. The FRET–AIE approach can be a useful addition to the spectrum of available methods for monitoring drug release from stimuli-responsive nanomedicine.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Yue Yang,Kaiqing Yun,Yunjian Li,Ling Zhang,Wenxuan Zhao,Zhihong Zhu,Baocheng Tian,Fen Chen,Weisan Pan
Integration of multiple therapies into one nanoplatform holds great promise to overcome the shortcomings of traditional single-modal therapy and achieve favorable antitumor efficacy. Herein, we constructed a dual receptor-targeting nanomicelle system with GSH-responsive drug release for precise fluorescence imaging and superior chemo-phototherapy of cancer. The synthetic amphiphilic hyaluronic acid derivative (FHSV) could self-assemble into nanomicelles in aqueous media. Then, paclitaxel (PTX) and photosensitizer IR780 iodide (IR780) were co-loaded into the micelles by a simple dialysis method. The resulting IR780/PTX/FHSV micelles with a particle size of 150.2 ± 6.9 nm exhibited excellent stability, GSH-responsive drug release and good photothermal/photodynamic efficacy. Once accumulated at the tumor sites, IR780/PTX/FHSV micelles efficiently entered tumor cells through receptor-mediated endocytosis and then rapidly release PTX and IR780 under GSH-rich tumor microenvironment . Upon NIR laser irradiation, IR780 produced local hyperthermia and sufficient reactive oxygen species to promote tumor cells apoptosis and necrosis. The results of in vitro and in vivo experiments consistently demonstrated that compared with single chemotherapy and phototherapy, the chemo-phototherapy could more efficiently kill tumor cells by synergistic antitumor effect. Therefore, our study provides a novel and efficient approach for multimodal treatment of malignant tumor.
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JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
You Li,Man Li,Tao Gong,Zhirong Zhang,Xun Sun
Increasing attention has been paid to nasal delivery. Subunit vaccines based on antigenic proteins or polypeptides offer good safety. However, lack of delivery efficiency, particularly for nasal immunization, is a big issue. Here we designed a highly tunable polymeric hybrid micelle (PHM) system offering good vaccine efficacy after nasal administration . PHMs are formulated from two amphiphilic diblock copolymers , polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG), the ratio of which determines PHM physicochemical properties. Citraconic anhydride-modified ovalbumin (Cit-OVA), as model antigen, was incorporated into PHMs via electrostatic interaction , giving antigen-loaded micelles of around 150 nm in size. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by adjusting the mass ratio of PCL-PEG and PCL-PEI. PHM/Cit-OVA complexes containing PCL-PEI and PCL-PEG in a 1:1 mass ratio induced strong immune responses in nasal mucosa and serum in vivo without causing obvious toxicity, and Cit-OVA was efficiently internalized by dendritic cells. These results demonstrate the promise of this multifunctional polymeric delivery system for nasal vaccination.
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Science of Advanced Materials
·
2017
·
IF 1.671
Zhang Xiong,Li Yuebin,Cai Yaxuan,Zhang Yi,Tian Yiqun,Wang Lin,Gu Haoshuang,Chen Wei
Fluorescent dye-doped silica nanoparticles (FDSNPs) have exhibited great potential in applications including solid-state lighting, chemical sensing, and biological theranostics. However, the wide application of FDSNPs is still a big challenge due to the lack of efficient synthesis strategy.
Herein, red fluorescent hybrid silica nanocapsules (FHSNCPs) were assembled by a green, convenient, and benign method based on Pluronic®F127 micelles as a soft template. Morphologies, structures, sizes, and fluorescence properties of the as-prepared silica nanocapsules were
characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR) and fluorescence spectroscopy. The size of the silica nanocapsules was well controlled from 20.5 nm to 23.6 nm by varying the concentration of F127 and tetramethylorthosilicate
(TMOS). Further investigations reveal that these nanocapsules exhibit monodisperse size, stable aqueous dispersibility, and novel optical properties, which show great potential for fluorescence imaging and temperature monitoring in biological tissues.
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MACROMOLECULAR BIOSCIENCE
·
2017
·Vol. 17
·期 8
·1700114
·
IF 3.238
Ting Wu,Longhai Wang,Shenggang Ding,Yezi You
A novel PEGylation polypeptide, poly(ethylene glycol)- b -poly( l -lysine)- b -poly( l -cysteine) (PEG-PLL-PCys) triblock copolymer is synthesized via the sequential ring-opening polymerization of amino acid N -carboxyanhydrides initiated by methoxypolyethylene glycol amine (mPEG-NH 2 , M w is 2 kDa). Subsequently, the obtained polypeptide is partially conjugated with fluorocarbon chains via disulfide exchange reaction. PLL segment can condense plasmid DNA through an electrostatic force to form a complex core, PEG segment surrounding the complex like a corona can prevent the complex from precipitation and reduce the adsorption of serum, while PCys segment with fluorocarbon can enhance the cellular uptake and the stability of the formed polyplex micelles in physiological conditions. Experiment results exhibit that the fluorinated polypeptides have low cytotoxicity and good gene transfection efficiency even in the presence of 50% fetal bovine serum.
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REACTIVE & FUNCTIONAL POLYMERS
·
2020
·
IF 3.333
Shupeng Li,Wei Zhao,Na Liang,Yingxue Xu,Yoshiaki Kawashima,Shaoping Sun
The clinical application of paclitaxel (PTX) is limited due to its low solubility and severe side effects. In this study, an amphiphilic graft copolymer based on mPEG , deoxycholic acid and N -acetyl- L -cysteine modified hyaluronic acid (mPEG-HA(DCA)-NAC) was synthesized and used as a redox-sensitive nano-sized drug delivery system. The polymer was characterized by Fourier transform infrared (FT-IR) and Proton nuclear magnetic resonance ( 1 H NMR) analysis. As an amphiphilic polymer, mPEG-HA(DCA)-NAC could self-assemble into micelles in aqueous milieu and encapsulate PTX in the hydrophobic core with high drug loading of 15.6% and high encapsulation efficiency of 73.8%. The PTX-loaded micelles had an average size of 147 nm and zeta potential of −38.3 mV. Physicochemical properties of the micelles were measured by TEM and XRD analysis . XRD analysis confirmed the successful encapsulation of PTX in an amorphous state. In vitro drug release study demonstrated the redox-sensitivity of the micelles. In vitro and in vivo antitumor efficacy study indicated that the PTX-loaded mPEG-HA(DCA)-NAC micelles had excellent antitumor effect but with low toxicity to the body. It can be concluded that the mPEG-HA(DCA)-NAC micellar system represents a promising nanocarrier for delivery of PTX.
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Drug Delivery and Translational Research
·
2020
·Vol. 10
·期 5
·1520-1530
·
IF 2.664
Cheng Ziting,Lin Hua,Wang Zhen,Yang Xiaoyu,Zhang Mei,Liu Xuechun,Wang Bingjie,Wu Zhenfeng,Chen Daquan
In order to improve the bioavailability of curcumin (Cur) and patient compliance, a type of novel hyaluronic acid (HA) composite microneedles containing Cur-loaded micelles was designed in this paper. On the one hand, the microneedles matrix solution was prepared by screening the optimal concentration of HA and the better proportion of HA to sodium carboxymethyl starch (CMS-Na). On the other hand, the amphiphilic polymer, named as Quercetin-Dithiodipropionic Acid-Oligomeric Hyaluronic Acid (Que-DA-oHA), was synthesized and characterized using 1 H-NMR. Subsequently, the dialysis method was used to prepare Cur-loaded Que-DA-oHA micelles with an average size of 172.6 ± 11.4 nm and zeta potential of − 33.71 ± 0.45 mV. A micromolding process was used to prepare the micelle-loaded HA composite microneedles. It had been found that when the concentration of HA was 200 mg/mL and the mass ratio of HA to CMS-Na was 2:1, the prepared HA composite microneedles had good mechanical strength. In-skin dissolution kinetics showed that the micelle-loaded HA composite microneedles could dissolve quickly in the skin. In vitro permeation study indicated that the microneedles delivered 74.7% of their drug load over 6 h, which exhibited remarkable drug permeation properties in a short time. Here, we creatively combined micellar technology with microneedle technology to rapidly deliver Cur transdermally for diseases treatment such as melanoma.
Graphical abstract
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Journal of Biomedical Nanotechnology
·
2020
·Vol. 16
·期 7
·1160-1168
·
IF 4.483
Liu Qiaoming,Cheng Meng,Liang Jianqin,Jin Yi,Feng Jianfang,Tu Liangxing
The oral administration of paclitaxel suffering obstacles like poorly solubility and low permeability, causing extremely low oral bioavailability. In this study, we aim to study the role of transmembrane pathway on the absorption mechanisms of PTX-Micelles. In addition, we will further
study the permeability of PTX-Micelles by employing in situ perfusion model. The results showed the PTX-Micelles could be up taken by caco-2 intact. In addition, we found that the endocytosis pathway and M cells pathway attended, while paracellular pathway absented in the transport
process of PTX-Micelles. The study on in situ perfusion showed the absorption rate constant (Ka) of PTX was enhanced from 6.3, 6.1, 10.6 and 13.6 × 10–2/min to 15.1, 18.4, 45.6 and 42.9 × 10–2/min by micelles in duodenum, jejunum, ileum
and colon, respectively, indicating the PTX-Micelles could enhance the permeability of PTX in intestinal membrane. This study indicating that transmembrane pathway-mediated transport is an important part in the transport process of polymeric micelles, and designing formulation based on transmembrane
pathways may be a promising route for oral bioavailability enhancement of poor-soluble drugs.
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Journal of Biomedical Nanotechnology
·
2014
·Vol. 10
·期 8
·1458-1468
·
IF 7.578
Li Xingyi,Chen Tongke,Xu Lu,Zhang Zhaoliang,Li Lingli,Chen Hao
Poor water solubility as well as poor bioavailability of curcumin has greatly hindered its applications in cancer therapy. In the present study, a highly water soluble curcumin nano-formulation was developed and its in vivo anti-cancer efficiency in nude BALB/c mouse model was
evaluated. Unlike native curcumin, the developed curcumin micelles were quickly dissolved into aqueous solution with significant improvement of water solubility (∼104 fold increasement compared to its native form). The developed curcumin micelles had a narrow size distribution
(18–28 nm) with high drug encapsulation efficiency (85%–95%). The developed curcumin micelles were characterized by X-raydiffraction (XRD), Differential scanning calorimetric (DSC), and Fluorescence spectral analysis. We observed the enhanced stability of curcumin in micelles formulation
in phosphate buffer solution (PBS). In vitro cytotoxicity assay indicated that the curcumin micelles was comparatively more effective than native curcumin against various cancer cell lines due to the enhanced cellular uptake of curcumin yet resulting in the apoptosis of cancer cells.
Western blotting study revealed that the induction apoptosis of S-65 cancer cells by curcumin micelles was mainly due to the down-regulation of p-Rb, Blc-2, p-AKT expression and caspase-9 activation. In vivo anti-tumor test in nude BALB/c mouse bearing S-65 xenografts indicated the
intraperitoneal injection of curcumin micelles (25 mg/kg) could significantly inhibit tumor growth as compared with native curcumin treatment (p < 0.05), which was accompanied by significantly increased apoptosis of tumor cells and diminished vascular endothelial growth factor expression
in tumor tissue (p < 0.05).
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