International Journal of Nanomedicine
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2022
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IF 7.033
Jiangxiu Niu,Ming Yuan,Zhaowei Zhang,Liye Wang,Yanli Fan,Xianghui Liu,Xianming Liu,Huiyuan Ya,Yansong Zhang,Yang Xu
Background The poor skin permeation and deposition of topical therapeutic drugs is a major issue in topical drug delivery, improving this issue is conducive to improving the topical therapeutic effect of drugs. Methods In this study, octadecylamine modified hyaluronic acid (OHA) copolymer was synthesized by amide reaction technique to prepare curcumin (CUR)-loaded micelles (CUR-M) for topical transdermal administration. CUR-M was successfully prepared by dialysis, and the formulation was evaluated for particle size, zeta potential, surface morphology, entrapment effciency (EE%), drug loading (DL), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the in vitro drug release. Additionally, in vitro skin permeation and retention, in vivo topical analgesic and anti-inflammatory activity, and skin irritation were assessed. Results The mean drug loading (DL), drug entrapment efficiency (EE), hydrodynamic diameter and zeta potential of CUR-M were 8.26%, 90.86%, 165.64 nm and −26.85 mV, respectively. CUR-M was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), it was found that there was an interaction between CUR and OHA, and CUR existed in CUR-M in an amorphous form. CUR-M exhibited sustained release in 48 h and good stability at 4 °C for 21days. CUR-M could significantly increase the skin penetration and retention of CUR and had better analgesic and anti-inflammatory activities in vivo when compared with CUR solution. Hematoxylin-eosin staining results revealed that the transdermal penetration mechanism of CUR-M might be related to the hydration of stratum corneum by HA. In addition, CUR-M showed no skin irritation to mouse skin. Conclusion CUR-M might be a promising and safe drug delivery system for the treatment of topical diseases.
研究领域:
药剂学
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皮肤科学
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生物材料
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 18
·10801
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IF 6.208
Wei Zhao,Zixue Li,Na Liang,Jiyang Liu,Pengfei Yan,Shaoping Sun
In the present study, an amphiphilic polymer was prepared by conjugating methoxy poly(ethylene glycol) (mPEG) with tetraphenylethene (TPE) via disulfide bonds (Bi(mPEG-S-S)-TPE). The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs such as paclitaxel (PTX) in the core. Combining the effect of TPE, mPEG, and disulfide bonds, the Bi(mPEG-S-S)-TPE micelles exhibited excellent AIE feature, reduced protein adsorption, and redox-sensitive drug release behavior. An in vitro intracellular uptake study demonstrated the great imaging ability and efficient internalization of Bi(mPEG-S-S)-TPE micelles. The excellent anticancer effect and low systemic toxicity were further evidenced by the in vivo anticancer experiment. The Bi(mPEG-S-S)-TPE micelles were promising drug carriers for chemotherapy and bioimaging.Keywords:polymeric micelles;aggregation-induced emission;bioimaging;redox-sensitive;anticancer drug delivery
研究领域:
材料科学
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生物医学工程
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肿瘤学
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PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2023
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IF 10.2
Lijiao Yang,Shaomin Song,Meihui Yin,Min Yang,Daoping Yan,Xiaohui Wan,Jipeng Xiao,Yuchen Jiang,Yongchao Yao,Jianbin Luo
The appearance of multidrug-resistant bacteria and the formation of bacterial biofilms have necessitated the development of alternative antimicrobial therapeutics. Antibiotics conjugated with or embedded in nano-drug carriers show a great potential and advantage over free drugs, but the mass proportion of carriers generally exceeds 90% of the nano-drug, resulting in low drug loading and limited therapeutic output. Herein, we fabricated a nanocarrier using antibiotics as the building blocks, minimizing the use of carrier materials, significantly increasing the drug loading content and treatment effect. Firstly, we conjugated betaine carboxylate with ciprofloxacin (CIP) through an ester bond to form the amphiphilic conjugate (CIP-CB), which self-assembled into micelles (CIP-CBMs) in aqueous solutions, with a CIP loading content as high as 65.4% and pH-induced surface charge reversal properties. Secondly, a model photosensitizer (5, 10, 15, 20-tetraphenylporphyrin (TPP)) was encapsulated in CIP-CBMs, generating infection-targeted photodynamic/antibiotic combined nanomedicines (denoted as TPP@CIP-CBMs). Upon accumulation at infection sites or in deep bacterial biofilms, the ester bond between the betaine carboxylate and CIP is cleaved to release free TPP and CIP, leading to a synergetic antibacterial and antibiofilm activity in vitro and in vivo .
研究领域:
药理学
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微生物学
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纳米医学
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PubMed
高影响因子
MATERIALS & DESIGN
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2022
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IF 9.417
Lingli Jin,Yanwen Xu,Fengjiao Chen,Dingle Yu,Hongze Liang,Zhenjiang Liang,Ziyu Liu,Haiyan Li,Junying Liu,Hui Tan,Lingling Zhao
Mitochondria-targeted and pH-triggered charge-convertible polymeric micelles (GPTD) were developed for doxorubicin (DOX) delivery and targeted anticancer therapy. GPTD surface was negatively charged under physiological pH (7.4), while it converted to positive charge under tumor pH (6.8). Sustained release of DOX from the drug loaded polymeric micelles was observed and the drug release was accelerated by decreasing the medium pH from 7.4 to 6.8. Cellular uptake by U251 glioma cells showed that GPTD can enhance the accumulation of polymeric micelles inside the mitochondria after charge-mediated cellular internalization and release DOX into the cellular interior. In vivo anticancer activity performed on glioma Balb/c nude mice demonstrated that the DOX-containing GPTD could remarkably inhibit the tumor growth, and displayed a significant reduction of tumor tissue cells and fewer Ki67 positive cells compared to the PBS group. Hence, this mitochondrial targeted and pH-triggered charge-convertible polymeric micellar system showed substantial promise for anticancer therapy.
研究领域:
药剂学
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肿瘤学
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高影响因子
ACS Applied Nano Materials
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2023
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IF 5.9
Weihua Su,Yan Qin,Jianning Wu,Guihua Meng,Shengchao Yang,Lin Cui,Zhiyong Liu,Xuhong Guo
After cotton is invaded by cotton aphids and other pests, the function of its defense system decreases, and it is more vulnerable to infection by bacteria. When plants are invaded by external bacteria, they quickly produce reactive oxygen species (ROS). In this paper, ROS-responsive pesticide release carrier materials are designed and prepared for solving bacterial infections in plants by ring-opening polymerization of ε-caprolactone (ε-CL) and β-cyclodextrin (β-CD) to obtain a hydrophobic guest (β-CD-PCL). Thioketal (TK) was modified by adamantane (Ad) and poly(ethylene glycol) monomethyl ether (mPEG5000-OH) to form a hydrophilic guest (mPEG5000-TK-Ad). β-CD-PCL and mPEG5000-TK-Ad interact with each other to form an amphiphilic polymer (mPEG5000-TK-Ad@β-CD-PCL), which is loaded with carbendazim (MBC) by self-assembly (MBC-mPEG5000-TK-Ad@β-CD-PCL). The polymer had ROS response characteristics, and the release rate of C increased from 30 to 57% after 120 h of ROS stimulation. The inhibition rate of Rhizoctonia S. was 92.23% when the effective concentration of MBC was 30 mg/L. The critical micelle concentration (CMC) of the polymer is 8.30 mg/L, and the micelle had storage stability for at least 14 days, showing good storage stability. Therefore, this ROS-responsive polymer carrier has great potential as a carrier for antimicrobial pesticides.
研究领域:
植物病理学
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材料科学
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农业科学
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DOI
高影响因子
Drug Delivery and Translational Research
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2023
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IF 5.4
Jin Xingcheng,Xia Xiaoli,Li Jiaying,Adu-Frimpong Michael,Wang Xiaowen,Wang Qilong,Wu Huaxiao,Yu Qingtong,Ji Hao,Toreniyazov Elmurat,Cao Xia,Yu Jiangnan,Xu Ximing
At present, ulcerative colitis (UC) has become a global disease due to its high incidence. Hyperoside (HYP) is a naturally occurring flavonoid compound with many pharmacological effects. This study aimed to develop HYP-loaded mixed micelles (HYP-M) to improve oral bioavailability of HYP and to evaluate its therapeutic effect on UC. The prepared HYP-M exhibited stable physical and chemical properties, smaller particle size (PS) (21.48 ± 1.37 nm), good polydispersity index (PDI = 0.178 ± 0.013), negative Zeta potential (ZP) (− 20.00 ± 0.48 mV) and high entrapment rate (EE) (89.59 ± 2.03%). In vitro release and in vivo pharmacokinetic results showed that HYP-M significantly increased the releasing rate of HYP, wherein its oral bioavailability was 4.15 times higher than that of free HYP. In addition, HYP-M was more effective in the treatment of UC than free HYP. In conclusion, HYP-M could serve as a novel approach to improve bioavailability and increase anti-UC activity of HYP. Graphical abstract
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PubMed
高影响因子
TALANTA
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2023
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IF 6.1
Ying Sun,Qimeng Wu,Quanyou Fu,Hailin Cong,Youqing Shen,Bing Yu,Hao Hu
Combination chemotherapy is a common strategy to enhance treatment efficacy and avoid multidrug resistance (MDR) in clinical practice. However, it is difficult to ensure the co-enrichment and reasonable ratio of synergistic drugs in the lesion site after intravenous administration. Integrating synergistic drugs into a nanocarrier can improve drug stability, targeting, drug loading, and importantly, ensure that synergistic drugs work at one destination. This study uses 10-hydroxycamptothecin (HCPT) to construct a polymeric prodrug micelle , and the demethylcantharidin (DMC) is proportionally encapsulated within the micelle. Triggered by reactive oxygen species (ROS), HCPT and DMC were released simultaneously from the co-delivery platform in tumor cells. DMC promotes abnormal cell division by inhibiting the synthesis of the cell cycle checkpoint kinase Protein phosphatase 2A (PP2A), leading to increased cell vulnerability to DNA damage, disordered replication, and death. The co-delivery platform exhibited satisfactory biosafety and antitumor efficacy in vivo . The proposed co-delivery platform may provide a valuable reference for the translation of clinical combination chemotherapy regimens into nano-drug delivery systems.
研究领域:
药学
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肿瘤学
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纳米医学
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PubMed
高影响因子
Biomedical Materials
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2023
·Vol. 18
·期 4
·045005
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IF 4
Jian Zhang,Xiaoxiao Li,Xiaoli Xia,Michael Adu-Frimpong,Xinyi Shen,Qing He,Wanjing Rong,Feng Shi,Xia Cao,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu
In this regard, we developed vitexin (Vi)-loaded D-ɑ-tocopherol polyethylene glycol succinate, polyvinylpyrrolidone K30 and sodium cholate mixed micelles (Vi-MMs) mainly for improving oral bioavailability and enhancing anti-osteoporotic effect of Vi. Thin layer dispersion method was employed to prepare Vi-MMs, and then the optimal prescription was optimized by the orthogonal design-response surface method, wherein encapsulation efficiency (EE) was used as optimizing index. The physical properties of Vi-MMs such as appearance morphology, particle size, and zeta potential were also characterized. We further analyzed the in-vitro release of Vi and Vi-MMs in three media and investigated the pharmacokinetics of Vi and Vi-MMs in rats. Anti-osteoporotic activity of Vi and Vi-MMs was assessed by establishing a zebrafish osteoporosis model with prednisone. Drug loading, EE, particle size and zeta potential of the optimized Vi-MMs were 8.58 ± 0.13%, 93.86 ± 1.79%, 20.41 ± 0.64 nm and −10 ± 0.56 mV, respectively. The optimized Vi-MMs were shaped spherically as exhibited by transmission electron microscopic technique, with evident core shell nano-structure, well dispersed. In all three media, the release rate of Vi-MMs was significantly higher than that of free Vi. The oral bioavailability of Vi-MMs was increased by 5.6-fold compared to free Vi. In addition, alleviation of prednisone induced osteoporosis in zebrafish by Vi-MMs further demonstrated good anti-osteoporotic effect. In summary, Vi-MMs exhibited enhanced bioavailability and anti-osteoporotic effect, which is expected to be potential nanocarrier for Vi applications in drug development.
研究领域:
药学
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纳米技术
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药理学
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PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2023
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IF 19
Tiantian Chen,Yan Qin,Yao Li,Yaru Li,Jiajia Luo,Lanlan Fan,Meiyu Feng,Zheng Wang,Yanjun Zhao
The dose-dependent cardiomyopathy of adriamycin (doxorubicin) limits its long-term clinical use, which is revealed as a consequence of cardiomyocyte ferroptosis. As a ferrous iron (Fe 2 + )-dependent regulated cell death pathway, ferroptosis is induced by the tailored lipid peroxides in the cell membranes. Herein, iron-chelating polymer micelles are reported for concurrent doxorubicin delivery and cardiotoxicity reduction. The amphiphilic polymer consists of methoxy poly (ethylene glycol)- co -poly (glutamic acid) copolymer as the backbone and deferiprone analog as the side chain. The chiral polymer adopted the α-helix conformation to enable prolonged retention in the cell membranes, resulting in efficient iron chelation, ferroptosis inhibition, and cardiotoxicity reduction. The co-encapsulation of doxorubicin and coenzyme Q 10 (CoQ 10 ) in micelles further alleviates the cardiotoxicity because the reduced CoQ 10 can act as a radical trapping agent to constrain lipid peroxidation and cardiomyocyte ferroptosis. The reduction of cardiotoxicity is accompanied by enhanced anticancer efficacy in an in vivo murine breast cancer model. The chiral iron-chelating polymer micelles can be a promising platform for enhanced doxorubicin delivery and reduced cardiac adverse effects.
研究领域:
药学
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纳米技术
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心脏病学
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肿瘤学
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材料科学
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高影响因子
Journal of Materials Chemistry B
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2023
·Vol. 11
·期 38
·9246-9259
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IF 7
Fusheng Zhang,Gongcui Pei,Baihao Huang,Jianchang Xu,Lijuan Zhang
π–π stacking strategies can enhance the stability performance of delivery platforms but are often restricted by incomplete drug release performance, even with the help of crosslinking strategies. Therefore, there has been considerable interest in enhancing the drug release performance by disrupting the π–π stacking region (structural rearrangements). Herein, we synthesized poly(3-(isobutyloxy)-2-oxopropyl benzoate)-b-poly(2-hydroxybutyl methacrylate)-co-poly((ethylene glycol)methylether methacrylate) [PBOOPMA-b-P(HBMA-co-PEGMA), PHB] and revealed the drug release mechanism of PHB-based micelles. The structural rearrangements derived from the crosslinking strategy were revealed to improve the early release performance by 43–55% using micellar dissolutions. Moreover, the esterase-responsive strategy was elucidated to induce reassembly with 77–79% size variation, intensifying the structural rearrangements, which was also synergistic with the crosslinking strategy. Based on the advantages of improving drug release performance, the esterase-responsive strategy was considered a promising candidate for enhancing late release performance. Meanwhile, it is believed that such responsive modulation (crosslinking, esterase-responsive) in the π–π stacking region will become highly promising for subsequent research. Finally, the biosafety of 95.81% at 400 mg L−1 and drug cytotoxicity of IC50 ≈ 2.5 mg L−1 of PHB-EDE@CPT were also validated, confirming the broad application prospects of PHB-based crosslinked micelles.
研究领域:
药剂学
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生物材料科学
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DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Wenqing Zang,Duo Gao,Miaorong Yu,Manmei Long,Zhuan Zhang,Tianhai Ji
The clinical utility of gemcitabine, an antimetabolite antineoplastic agent applied in various chemotherapy treatments, is limited due to the required intravenous injection. Although chemical structure modifications of gemcitabine result in enhanced oral bioavailability, these modifications compromise complex synthetic routes and cause unexpected side effects. In this study, gemcitabine-loaded glycocholic acid-modified micelles (Gem-PPG) were prepared for enhanced oral chemotherapy. The in vitro transport pathway experiments revealed that intact Gem-PPG were transported across the intestinal epithelial monolayer via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway. In mice, the pharmacokinetic analyses demonstrated that the oral bioavailability of Gem-PPG approached 81%, compared to less than 20% for unmodified micelles. In addition, the antitumor activity of oral Gem-PPG (30 mg/kg, BIW) was superior to that of free drug injection (60 mg/kg, BIW) in the xenograft model. Moreover, the assessments of hematology, blood chemistry, and histology all indicated the hypotoxicity profile of the drug-loaded micelles.
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高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Yanjie Xu,Hui Chen,Xuefeng Liu,Yinjun Fang
In order to elucidate the possibility of the formation and enzymatic dissociation of worm-like micelles (WLMs) from long-chain alkanoylcholines (LCACs), strategies of fabrication and butyrylcholine esterase (BChE)-catalyzed dissociation of LCAC-based WLMs have been developed. Three LCACs with different hydrophobic tail lengths, namely dodecanoylcholine bromide (DCB), myristoylcholine bromide (MCB), and palmitoylcholine bromide (PCB), have been used as model cationic surfactants . It was demonstrated that the hydrophobic tail length of an LCAC played an important role in the formation of WLMs. With the assistance of sodium salicylate (NaSal), DCB proved to be incapable of efficiently forming WLMs, whereas MCB and PCB performed well. PCB-based WLMs have also been fabricated with the aid of NaNO 3 . To fabricate WLMs at a surfactant concentration of 0.1 mol L −1 , the optimal molar ratio of the additive (NaSal and NaNO 3 ) to the surfactant (MCB and PCB) was around 0.83 (NaSal/MCB), 0.63 (NaSal/PCB) and 20 (NaNO 3 /PCB), respectively. The respective average diameters of the WLMs were about 4.11 nm (MCB-NaSal), 4.82 nm (PCB-NaSal), and 4.51 nm (PCB-NaNO 3 ). Meanwhile, the respective zero-shear viscosities of the WLMs were about 5.38 × 10 2 mPa s (MCB-NaSal), 1.81 × 10 5 mPa s (PCB-NaSal), and 7.35 × 10 4 mPa s (PCB-NaNO 3 ). Jelly-like PCB-NaSal and PCB-NaNO 3 WLMs underwent efficient dissociation through a BChE-catalyzing strategy under mild conditions of pH 7.4 and 37 °C. Its chemical principle was a hydrolysis reaction of PCB catalyzed by BChE.
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高影响因子
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