COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Lu Xu,Xu Xu,Hao Chen,Xingyi Li
Polymeric nanoparticles have been developed to improve the bioavailability of drugs applied in ocular drug delivery. However, there are few information on ocular biocompatibility of polymeric nanoparticles applied topically onto the eye. In this paper, the ocular biocompatibility and tolerance of methoxy poly(ethylene glycol)–poly(ɛ-caprolactone) (MPEG–PCL) micelles (∼50 nm) were investigated in rabbit eyes after a single intracameral and intravitreal injections. In vitro cytotoxicity assays showed that MPEG–PCL micelles had no apparent cytotoxicity against human corneal epithelial cells (HCEC), human lens epithelial cells (HLEC), and retinal pigment epithelial cells (RPE cells) at micelle concentrations of 0–2 mg/mL. After a single intracameral injection of 0.2 mL MPEG–PCL micelles (200 mg/mL) into rabbit eyes, MPEG–PCL micelles were slowly removed from aqueous humor in a period of 14 days, while the intraocular pressure (IOP) was maintained at nearly the same level for 15 days. Three days after intracameral injection, dual staining of corneal endothelium showed that the endothelial cells were nearly regular hexagon-shape with well-defined organization, similar to normal endothelial cells. Hematoxylin and eosin staining indicated that there was absence of any obvious changes in microstructure of the corneal tissue and retina after a single intracameral and intravitreal injection of 0.2 mL MPEG–PCL micelles (100 mg/mL, 150 mg/mL, and 200 mg/mL). This study provides valuable information (safety and biocompatibility) for biomedical researchers to develop MPEG–PCL micelles as candidates for ocular drug delivery.
研究领域:
药学
·
眼科
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2013
·
IF 3.172
Qiongbo Zhou,Ding Gao,Jun Liu,Xuzhuo Sun,Lei Zhang,Bin Qi,Haibo Zhang,Chunlan Xia,Xiaohai Zhou
Spontaneous formation of supramolecular vesicles which are triggered by the formation of [4]pseudorotaxane B was demonstrated, whereas both Guest and [2]pseudorotaxane A, the precursors of [4]pseudorotaxane B, only assemble into micelles in DMF/water solution. The remarkable transformation of Guest from micelles to supramolecular vesicles was confirmed through DLS , TEM , and Cryo-TEM experiments. The cumulative release of a model drug, 5-carboxyfluorescein (CF), was used to determine the permeability of the supramolecular vesicles. No leakage of entrapped CF was observed within 48 h by fluorescence measurement, indicating the high stability of supramolecular vesicles. The formation mechanism of supramolecular vesicles self-assembled by [4]pseudorotaxane B was also discussed. In [4]pseudorotaxane B, CB[6] is used to increase the hydrophobic property of site β , which acts as hydrophobic “tail.” Meanwhile, CB[7] plays the role of increasing “head area” of site α , which acts as hydrophilic “head.” The synergistic effect of CB[6] and CB[7] induces the formation of supramolecular vesicles. Moreover, the effect of DMF content was investigated by TEM observations. It was found that the [4]pseudorotaxane B can self-assemble into regular supramolecular vesicles when the DMF content is in the range of 50–70%.
研究领域:
化学
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Yan-Ling Luo,Xiao-Li Yang,Feng Xu,Ya-Shao Chen,Bin Zhang
Two kinds of thermo-sensitive poly(N-isoproplacrylamide) (PNIPAM) block copolymers, AB 4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with hydroxyl-terminated polybutadiene (HTPB) as central blocks, and characterization was performed by 1 H NMR, FT-IR and SEC . The multiblock copolymers could spontaneously assemble into more regular spherical core–shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension technique, nano particle analyzer, TEM, DLS and UV–vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature about 33–35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles.
研究领域:
高分子化学
·
药物传递系统
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2014
·
IF 2.784
Dong Zheng,Yuan
Yuan An,Shuhua Yang,Wei Wu,Weihua Xu,Guohui Liu,Cao Yang,Yang Dan,Zushun Xu,Shuilin Wu
Amphiphilic copolymers P(PBA)-g-P(PEG) containing poly(phenylboronic acid) (PPBA) and poly(ethylene glycol) (PEG) side chains were synthesized by copolymerization of 4-vinylphenylboronic acid (PBA) and poly(ethylene glycol) methyl ether methacrylate. The surface tension results showed that the critical micelle concentration (CMC) of P(PBA)-g-P(PEG) was 0.09 g/L. TEM revealed that these copolymers self-assembled into regular sphere micelles above CMC. The photon correlation spectroscopy suggested that they had unique performance of thermo-induced self-assembly. Above critical micelle temperature, they self-assembled into monodisperse micelles with thermosensitivity. Hydrodynamic diameters of these micelles increased dramatically in the presence of glucose. The glucose-regulated drug release behavior was observed through UV-vis spectroscopy.
研究领域:
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2024
·
IF 3.6
Yunjing Jia,Yuli Li,Mingzhu Wang,Fuyou Wang,Qingmin Liu,Zhimei Song
Considering cellular uptake promotion of lecithin and high expression of phospholipase in S. aureus, we designed curcumin (Cur)-loaded soy lecithin-based mPEG-PVL copolymer micelles (MPPC). The effect of soy lecithin on the anti-S. aureus activity of the formulation was studied with cur-loaded mPEG-PVL micelles (MPC without soy lecithin) as control. It was found that MPPC enhanced the water-solubility of Cur, and showed slow and sustained release behavior of Cur. Although MPPC had the same anti-S. aureus activity as Cur, its activity was significantly higher than MPC due to the cellular uptake promotion of soybean lecithin. It was noted that MPPC had good inhibition or destruction effect on biofilm, significant cell membrane damage, strong inhibition effect on protease or lipase production, and obvious induction effect on ROS expression when compared with Cur and MPC. So, the introduction of soy lecithin could improve the antibacterial activity of Cur. The lecithin-based micelles would offer potential to deliver antibacterial drugs for improved therapeutic action.
研究领域:
药剂学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2026
·
IF 4.7
Pingping Zhao,Wenhao Yuan,Yuhong Xu,Caifei Jin,Chu Chu,Yan Yang
The transdermal delivery of poorly water-soluble drugs is limited by low aqueous solubility and the stratum corneum permeability barrier. In this study, curcumin was formulated into self-assembled micelles using Tween 20 and polyethylene glycol 400, which exhibited a particle size of 12.5 nm, a zeta potential of −12.5 mV, and a 170-fold increase in solubility. The curcumin micelles (CM) were combined with constant-current iontophoresis (0.45 mA/cm2), to investigate the synergistic enhancement effects and underlying mechanisms. The results showed a 44.2-fold increase in cumulative release over 60 min, with a linear flux–current density relationship (R2 = 0.99). CM exhibited electro-responsive release with an approximate 20-min lag. Under a fixed 2 h total stimulation, pulsed current (4 pulses) nearly doubled the 8-h cumulative release compared to continuous current. Furthermore, both current density and electrode configuration were shown to influence penetration depth and width. Iontophoresis enabled CM to penetrate rat skin to a depth of 270 μm and increased intradermal retention by 258%. In a rat second-degree burn model, the combination therapy significantly accelerated wound healing via promoting angiogenesis, downregulating inflammatory cytokines, and enhancing collagen deposition.
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Jiaojiao Chen,Yarong Song,Wenqian Yang,Jianhui Guo,Saihui Zhang,Dong Wan,Yonghui Liu,Jie Pan
Chemotherapy remains the primary treatment for cancer; however, conventional chemotherapeutic drugs have several shortcomings, including poor solubility, lack of targeting, low bioavailability, and high toxicity to healthy tissues. In order to overcome these limitations, drug delivery systems (DDS) have emerged as a promising alternative. In this study, we synthesized TPGS3350-PVGLIG-SS-DOX polymeric micelles that incorporate both extracellular MMP2/9 enzyme response and intracellular reduction response at a nanoscale level. The micelles remained stable throughout the blood circulation and only aggregated at the tumor sites, thanks to the enhanced permeability and retention (EPR) effect. Moreover, the tumor tissue showed a high expression of MMP2/9 enzymes, which resulted in the cleavage of the PVGLIG peptide sequence, ultimately leading to an improved phagocytosis efficiency. Under the action of high intracellular GSH concentration, the disulfide bond was broken and DOX was released to induce tumor cell death. The TPSD&D micelles exhibited good tumor inhibitory activity in vivo and significantly reduced toxic side effects on normal tissues. Our work provides a simple method to assemble tumor-targeted prodrug micelles to improve cancer therapy, which holds potential for clinical applications in antitumor therapy.
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Jinyu Liu,Yanhao Zhang,Chao Liu,Yuhao Jiang,Zihao Wang,Xinsong Li
Polypeptides are a highly promising carrier for delivering hydrophobic drugs, due to their excellent biocompatibility , non-toxicity, and non-immunogenicity. Herein, a redox and pH dual-responsive poly(ethylene glycol)-SS-b-polypeptide micelles encapsulated with disulfide bridged paclitaxel-pentadecanoic acid prodrug was developed for cancer chemotherapy . First of all, disulfide bridged paclitaxel-pentadecanoic acid prodrug (PTX-SS-COOH) and poly(ethylene glycol)-SS-b-polylysine-b-polyphenylalanine (mPEG-SS-b-PLys-b-PPhe, ESLP) were synthesized and confirmed via NMR, MS, FT-IR or GPC. After that, PTX-SS-COOH (PSH) embedded mPEG-SS-b-PLys-b-PPhe (ESLP/PSH) micelles were prepared by mixing method based on electrostatic interactions and hydrophobic forces. For comparison, mPEG-b-PLys-b-PPhe (ELP) was mixed with PTX-SS-COOH to generate another kind of micelles (ELP/PSH). The characterization of ESLP/PSH micelles through dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed a spherical structure with a diameter of approximately 170 nm . It is noteworthy that ESLP/PSH micelles displayed a high drug-loading rate of 22.84%, and excellent stability, which can be attributed to the specific interactions between the prodrug and copolymer . Drug release analysis demonstrated that the micelles exhibited a substantial release of PTX in the presence of GSH at pH 5.0, indicating a pH and redox dual responsiveness. In vivo pharmacokinetic study revealed the ESLP/PSH micelles had increased bioavailability and an extended circulation time. Ultimately, antitumor efficacy and systemic toxicity evaluation in 4 T1 tumor-bearing mice confirmed that ESLP/PSH micelles achieved the highest level of tumor growth inhibition (ca. 83%) and the lowest systemic toxicity in comparison with ELP/PSH micelles and commercialized Taxol®. Taken together, the dual responsive micelles represent a promising PTX formulation with potential clinical application in cancer chemotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 2
·1-16
·
IF 3.3
Wu Wenting,Ding Quan,Zhou Zhiwei,Kuang Wenliang,Jiang Lipeng,Liu Peng,Ai Weiping,Zhu Weifeng
In order to better promote the application of the polymeric mixed micelles (PMMs) in oral delivery, in addition to focusing on the improvement of micellar structural stability, it is necessary to obtain the absorption characteristics of the intact micellar particles. In this work, the transport behavior across Caco-2 cells of FS/PMMs composed of Pluronic F127 and Solutol HS15 was tracked by encapsulating an environment-responsive probe into the particles. The specific property of the probe is the water-initiated aggregation-caused quenching (ACQ) ability, by which integral particles can be identified accurately. The influence of polymeric ratios (FS) on the transcellular behavior of FS/PMMs was explored and the single pass intestinal perfusion experiment was used to further illustrate it. Moreover, pharmacokinetics parameters were detected to analyze the relationship among FS ratios, transport behavior, and pharmacokinetic parameters. FS ratios were found to hardly affect the endocytosis pathways and intracellular itinerary of FS/PMMs, but do affect the proportion of each path. FS/PMMs with high HS15 content, namely System-I, were found to primarily undergo receptor-mediated endocytosis pathway and be less susceptible to lysosomal degradation, which would lead to more absorption and higher Cmax and AUC than drug suspension. In contrast, despite System-II with high F127 content cannot contribute to drug plasma concentration, it can prolong the in vivo retention time. These findings provided evidence for the role of polymeric ratios in modulating the transcellular absorption and pharmacokinetic parameters of the drug-loaded PMMs, and would be a step forward in helping PMMs’ design to enhance oral drug delivery. Graphical Abstract
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yanhai Xi,Tingwang Jiang,Yinglan Yu,Jiangmin Yu,Mintao Xue,Ning Xu,Jiankun Wen,Weiheng Wang,Hailong He,Yan Shen,Daquan Chen,Xiaojian Ye,Thomas J Webster
Introduction Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity.Methods The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied.Results The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR.Conclusion The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
·
IF 4.8
Qin Guo,Jie Cai,Pengyu Li,Dongling Xu,Xiaomin Ni,Hui Wen,Dan Liu,Suizhen Lin,Haiyan Hu
Androst-3β,5α,6β-triol (Triol) is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC) after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of drug-loaded mixed micelles.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Liu Zhanbiao,Chen Xuejun,Jin Qian,Li Min,Zhu Siqing,Zhang Yi,Zhi Defu,Zhao Yinan,Li Liqin,Zhang Shubiao
Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo, with IC50 values of 1.943 μg/mL for dHAD-PTX and 1.874 μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs.
✓ 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）