PHARMACEUTICAL RESEARCH
·
2018
·Vol. 35
·期 1
·1-15
·
IF 3.335
Jin Ya,Wu Zimei,Li Caibin,Zhou Weisai,Shaw John P.,Baguley Bruce C.,Liu Jianping,Zhang Wenli
Purpose To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration. Methods ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG 2000 ) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers. Stability of micelles was optimized in terms of critical micelle concentration (CMC) and drug release properties. The encapsulation efficiency (EE) and drug loading were determined using an established dialysis-mathematic fitting method. Multicellular spheroids (MCTS) penetration and cytotoxicity were investigated on MCF-7 cell line. Pharmacokinetics of ASL-micelles was evaluated in rats with ASL-solution as control. Results The ASL-micelles prepared with DSPE-PEG 2000 and TPGS (1:1, w /w) exhibited small size (~18.5 nm), higher EE (~94.12%), better sustained in vitro drug release with lower CMC which may be ascribed to the interaction between drug and carriers. Compared to free ASL, ASL-micelles showed better MCTS penetration capacity and more potent cytotoxicity. Pharmacokinetic studies demonstrated that the half-life and AUC values of ASL-micelles were approximately 1.37-fold and 3.49-fold greater than that of free ASL. Conclusions The optimized DSPE-PEG 2000 /TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor.
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Pharmaceutics
·
2024
·Vol. 16
·期 9
·1174
·
IF 4.9
Siying Huang,Simeng Xiao,Xuehao Li,Ranran Tao,Zhangwei Yang,Ziwei Gao,Junjie Hu,Yan Meng,Guohua Zheng,Xinyan Chen
Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC.
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Materials
·
2024
·Vol. 17
·期 12
·2901
·
IF 3.1
Ting-Ting Yu,Fu-Rong Yang,Yao Su,Yi-Heng Qi,Yi Liu,Nan Hu
Prolamins, proteins derived from plants, have extensive applications in pharmaceutics and food science. Jiuzao is a byproduct of the Baijiu brewing industry, and is a great source of prolamin. Despite its importance, knowledge regarding the extraction techniques and the properties of prolamin derived from Baijiu Jiuzao (PBJ) remains limited. Reverse micelles (RMs) extraction offers an efficient and cost-effective method for purifying proteins. In the present study, prolamin was extracted from Baijiu Jiuzao using RMs extraction and subsequently characterized in terms of its secondary structure, morphology, and particle size distribution. Our findings indicate that the purified prolamin extracted using further RMs extraction possessed higher α-helix content (+13.25%), forming a large-scale protein network, and narrower particle size distributions compared to the crude prolamin obtained by NaOH-ethanol method. This research suggests that RMs extraction has potential applications in extracting prolamin from brewing industry byproducts, offering an environmentally friendly approach to Baijiu Jiuzao recycling.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Li Xiang,Yuting Qin,Lei Li,Xianjing Xiang,Wenhui Zhang,Qiangqiang Jiao,Yaru Shao,Xinqiong Huang,Meichun Wu,Tianle Zhou,Yukang Lin,Yuping Chen
Liver fibrosis is a pathological condition marked by the excessive buildup of extracellular matrix primarily resulting from the transformation of quiescent hepatic stellate cells (HSCs) to myofibroblastic (MF) phenotype and their resultant over-expansion. Activated HSCs completely rely on their hyperactive mitochondria to supply the energy and biomass for their rapid proliferation and collagen secretion, so an intervention targeting their mitochondria can effectively restrict their pathological amplification and contribution to liver fibrosis. Here we tried sorafenib, a drug that plays anticancer roles by inducing the disruption and loss of mitochondrial functions, to reach an antifibrotic goal. And a complex micellar system, VA-PEG-PCL/TPGS (VPP/TPGS), was specifically designed and fabricated to encapsulate and deliver sorafenib selectively to activated HSCs to overcome its application limitations in bioavailability, toxicity and intracellular stay, and eventually maximize its induction of mitochondrial dysfunction and therapeutically antifibrotic efficacy. The prepared sorafenib complex micelles not only exhibited a suitable particle size, uniform morphology, and nice stability, but also performed excellently in the biosafety and HSCs-targetability in vitro and in vivo . In human active HSC cell lines, they markedly attenuated mitochondrial hyperactivity, induced apoptosis, and downregulated fibrosis markers as expected; while in a CCl 4 -induced murine model of hepatic fibrosis, they effectively restricted the expansion of MF-HSCs, reduced collagen deposition, and promoted the healing of liver damage, showing a good potential in fibrosis curation. Collectively, our VPP/TPGS complex micelles provide an ideal drug delivery platform that has the potential to revolutionize the treatment of liver fibrosis via addressing its cellular and metabolic underpinnings and thus improve patient outcomes.
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Frontiers in Veterinary Science
·
2025
·
IF 2.9
Yanling Sun,Yanan Mao,Xin He,Xinghua Zhao
The aim of this study was to prepare polymeric micelles composed of enrofloxacin (ENR) and methoxy poly (ethylene glycol)-poly(lactide) (mPEG-PLLA) using a solvent evaporation method to overcome the solubility-limited oral bioavailability of ENR. The formulation was optimized using a Box–Behnken design (BBD) to obtain ENR polymeric micelles (ENR-m) with high drug loading (DL, %) and entrapment efficiency (EE, %). The physicochemical properties, in vitro drug release, pharmacokinetics, and antibacterial efficacy were evaluated in comparison to pure ENR. ENR-m was successfully prepared and demonstrated satisfactory drug loading (68.38 ± 0.22%), entrapment efficiency (88.40 ± 0.91%), particle size (PS) (133.67 ± 3.10 nm), and polydispersity index (PDI) (0.13 ± 0.03). The ENR-m also exhibited excellent stability under environmental conditions (40°C and 75% relative humidity (RH)). In vitro release of ENR from micelles was accelerated in a PBS solution. A pharmacokinetic study on beagles revealed that the oral bioavailability of ENR-m was enhanced by approximately 1.60-fold compared to pure ENR (p < 0.01) and by 1.66-fold compared to commercially available tablets of ENR (p < 0.01). The antibacterial activity of ENR-m against Escherichia coli (E. coli) and Salmonella typhi (S. typhi) was stronger than that of pure ENR.
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ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Na Liu,Yanan Tan,Yingwen Hu,Tingting Meng,Lijuan Wen,Jingwen Liu,Bolin Cheng,Hong Yuan,Xuan Huang,Fuqiang Hu
Redox-responsive nanomaterials applied in drug delivery systems (DDS) have attracted an increasing attention in pharmaceutical research as a carrier for antitumor therapy. However, there would be unwanted drug release from a redox-responsive DDS with no selection at nontarget sites, leading to undesirable toxicities in normal tissues and cells. Here, an A54 peptide modified and PEGylated reduction cleavable glucolipid conjugate (A54-PEG-CSO-ss-SA, abbreviated to APCssA) was designed for intracellular delivery of doxorubicin (DOX). The synthesized APCssA could be assembled via micellization self-assembly in aqueous water above the critical micelle concentration (54.9 μg/mL) and exhibited a high drug encapsulation efficiency (77.92%). The APCssA micelles showed an enhanced redox sensitivity in that the disulfide bond could be degraded quickly and the drug would be released from micelles in 10 mM levels of glutathione (GSH). The cellular uptake studies highlighted the affinity of APCssA micelles toward the hepatoma cells (BEL-7402) compared to that toward HepG2 cells. In contrast with the nonresponsive conjugate, the drug was released from APCssA micelles more quickly in 10 mM level of GSH concentration (tumor cells). Moreover, the DOX-loaded APCssA micelles displayed an increased cytotoxicity which was 1.6- to 2.0-fold that of unmodified and nonresponsive micelles. In vivo, the APCssA micelles had stronger distribution to liver and hepatoma tissue and prolonged the circulation and retention time, while the drug release only occurred in the tumor tissue. The APCssA/DOX showed the tumor inhibition rate equal to that of commercial doxorubicin hydrochloric without negative consequence. This study suggested that the APCssA/DOX showed promising potential to treat the tumor for its special tumor targeting, selective intracellular drug release, enhanced antitumor activity, and reduced toxicity on normal tissues.
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Materials Today Bio
·
2025
·
IF 10.2
Ling Wang,Jie Li,Danya Zhang,Songwei Tan,Guiying Jiang,Xueqian Wang,Fei Li,Ying Zhou,Pingbo Chen,Rui Wei,Ling Xi
Metastasis and recurrence are the main causes of failure in the treatment of ovarian cancer (OC). Immunotherapy has brought new opportunities for cancer treatment, but the presence of the immunosuppressive tumor microenvironment limits its application in OC. Here, we prepared a kind of intelligent nanomicelles that could inhibit OC metastasis and recurrence by combining photothermal tumor ablation and immune remodeling. In this study, Indocyanine green (ICG), a photosensitizer and Monophosphoryl lipid A (MPLA), a Toll-like receptor 4 agonist, were encapsulated into the core of PEG-PLGA nanocarrier, and the surface was further modified with tumor-targeting peptide TMTP1. The formed TP1-IM nanomicelles with enhanced tumor accumulation could enable robust photothermal ablation of the primary tumor, and induce immunogenic cell death, release tumor-associated antigens, and DAMPs to form an endogenous in situ tumor vaccine by a single intravenous injection, which could effectively inhibit the growth of OC. Moreover, PTT with TP1-IM nanomicelles in combination with programmed cell death ligand 1 (PD-L1) checkpoint blockade could induce strong anti-tumor immune responses, relieve the immunosuppressive tumor microenvironment, and thus effectively inhibit the metastasis of OC. In addition, the combination strategy could produce long-term immune memory effects in treated mice to prevent the recurrence of tumors. Our work provides a new and individualized strategy for the treatment of OC and is expected for clinical transformation in the future for most components are clinically approved.
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2025
·
IF 2.8
Zhe Zong,Wei Zhao,Siyi Li,Na Liang,Shaoping Sun
A novel polymer Bio-CD-SS-TPE is designed and synthesized by modifying hydroxypropyl-β-cyclodextrin with the aggregation-induced emission (AIE) featured tetraphenylethylene derivative, disulfide bond, and biotin. The polymer can self-assemble into micelles in an aqueous phase and encapsulate paclitaxel (PTX) in the hydrophobic core. As expected, the Bio-CD-SS-TPE micelles exhibit excellent AIE performance and cell imaging capability. With the effect of disulfide bonds, the PTX-loaded micelles quickly release the drug upon the trigger of glutathione. In vivo study indicates the superior tumor inhibition effect and lower systemic toxicity of the PTX-loaded micelles. The Bio-CD-SS-TPE micellar system holds great potential in cancer treatment and bioimaging.
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RSC Advances
·
2016
·Vol. 6
·期 67
·62478-62484
·
IF 3.289
Wen'en Li,Haibo Wang,Zeliang Wei,Juewei Ning,Limei Ma,Huajie Zheng,Hai Niu,Wen Huang
To improve the effect of thrombosis therapy, an amphiphilic supramolecular prodrug consisting of diosgenin derivative (theophylline–diosgenin) and uracil-terminated poly(ethylene glycol) (PEG-U) was designed and synthesized successfully. The prodrug could self-assemble into micelles which was not only enhanced the drug solubility but also prolonged systemic circulation. Bleeding time assay confirmed that the micelles have a better antithrombotic activity compared to diosgenin in vivo, and platelet aggregation assay in vitro got the same results. The low cytotoxicity of supramolecular copolymer micelles was confirmed by MTT assay against LO2/HK-2 cells and acute toxicity studies in mice. Based on these results, the supramolecular prodrug micelles are very promising candidates for thrombosis therapy.
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Biomaterials Science
·
2020
·Vol. 8
·期 20
·5739-5750
·
IF 6.183
Sihui Wei,Guilan Quan,Chao Lu,Xin Pan,Chuanbin Wu
Photothermal therapy (PTT) based on aggregation-induced emission luminogen (AIEgen) is very promising for superficial tumor therapy due to the superior photostability and photothermal conversion efficiency of AIEgens. However, the systemic administration of AIEgen remains challenging, mainly because of solubility dissatisfaction and biodistribution. Here, a dissolving microneedle (MN) system loaded with AIEgen (NIR950) was developed for topical administration to treat malignant skin tumor melanoma. Firstly, NIR950-loaded polymeric micelles (NIR950@PMs) were prepared via a nanoprecipitation method to increase the drug solubility. Then, micelles were concentrated on needle tips of MN (NIR950@PMs@MN) by a two-step molding method. NIR950@PMs showed no distinct decline in emission intensity under continuous laser irradiation for an hour. Moreover, the pH-responsive micelles can be protonated in an acidic tumor microenvironment to facilitate the intracellular uptake. By virtue of dissolving MN, NIR950@PMs could rapidly accumulate at the tumor site and reach a suitable temperature for killing cancer cells under laser irradiation. With only single administration and one-time laser irradiation, the NIR950@PMs@MN could notably eliminate melanoma tumors with a low dose of NIR950. Overall, this dissolving MN system loaded with NIR950 showed remarkable photostability and also achieved a valid photothermal effect, which indicate great potential for clinical superficial tumor therapy.
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Expert Opinion on Drug Delivery
·
2014
·
IF 4.116
Yong-Yan Bei,Zhi-Qiang Yuan,Liang Zhang,Xiao-Feng Zhou,Wei-Liang Chen,Peng Xia,Yang Liu,Ben-Gang You,Xiao-Juan Hu,Qiao-Ling Zhu,Chun-Ge Zhang,Xue-Nong Zhang,Yong Jin
Backgroud: Polymeric micelles is a safe and effective delivery system, which belong to the targeted delivery system (TDS). An anticancer drug, harmine(HM) is a hydrophobic drug with much adverse effects when used for treatment of liver cancer. Chitosan (CS) is a polysaccharide and can be modified to be an amphiphilic polmer which could self-assemble into micelles and be applied for delivery of hydrophobic drugs. Objectives: To synthesize three kinds of novel biodegradable polymers, designated as palmitoyl-trimethyl-CS (TPCS)1, TPCS2 and Lac-TPCS2, and investigate their efficiency and mechanism of delivery HM to liver tumors in vitro and in viro. Results: The self-assembled micelles presented satisfactory particle size (∼ 200 nm) and drug release characteristics in vitro. It's proved that Lac-TPCS2/HM may enter HepG2 cell through endocytosis. Antitumor experiments in vivo revealed that Lac-TPCS2/HM could significantly inhibit tumor growth and extend the lifetime of mice bearing H22 tumors after intravenous administration. Subsequently in vivo near-infrared fluorescence imaging results demonstrated a satisfactory liver tumor-targeting effect of Lac-TPCS2/HM. Conclusion: Three novel polymers hold great potential in the development of nanomedicine for treatment of liver tumors, in particular Lac-TPCS2 exhibits the greatest antitumor potential through active target effect.
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Journal of Environmental Chemical Engineering
·
2025
·Vol. 14
·期 1
·120981
·
IF 7.2
Xiaohan Meng,Junfan Niu,Qing Guo,Gang Tang,Gaohua Hu,Weiyao Yan,Xiaohong Zhang,Yuqi Huang,Jianhua Xiao,Yongqian Liang,Ruyue Han,Guangyao Yan,Jianqiang Li,Yongsong Cao
To mitigate the dependency on toxic auxiliary agents in pesticide formulations and enhance bioactivity, a novel functional polymeric micelle carrier was engineered through the synthesis of graft-modulated, amphiphilic quaternary ammonium polyethyleneimine (QPEI). A series of QPEI polymers were synthesized by conjugating polyethyleneimines (PEIs) of varying molecular weights (600, 1800, and 10,000) with different acyl chlorides (palmitoyl, propionyl, and benzoyl). From this library, pal-QPEI 600 emerged as the optimal candidate to encapsulate the hydrophobic fungicide pyraclostrobin (PYR) for preparation of pesticide-loaded micelles (PYR@QPEI) duo to the highest quaternization degree, the lowest surface tension (35.04 mN/m), and the most potent antimicrobial activity. The resulting PYR@QPEI micelles were spherical and regular nanostructure with loading capacity of 7.02 % and superior interface performance on plant leaves and exhibited pH-responsive release behavior. In both in vitro and in vivo assays, PYR@QPEI showed good antifungal efficacy against Sclerotinia sclerotiorum compared to a commercial PYR suspension concentrate. The synergistic ratio between PYR and QPEI was calculated to be 1.74, confirming a synergistic antimicrobial effect. Furthermore, PYR@QPEI exhibited good storage stability, enhanced photostability, and high safety for plants with no significant genotoxicity. This study presents a smart, effective, and environmentally friendly nanopesticide delivery platform that reduces the need for toxic auxiliaries.
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