NEW JOURNAL OF CHEMISTRY
·
2020
·Vol. 44
·期 29
·12633-12638
·
IF 3.288
Weili Xue,Ashish Trital,Sihang Liu,Liangbo Xu
To simplify the preparation process and increase the drug-loading capacity of antitumor nanodrugs, doxorubicin-loaded micelles based on zwitterionic oligopeptides were fabricated through two step reactions in mild conditions. Zwitterionic oligopeptides Glu–Lys–Cys–Glu–Lys (EKCEK) were reacted with methacrylohydrazide (MAH) by click reaction, the product was further conjugated with doxorubicin (Dox) to form amphipathic molecules, and finally the amphipathic molecules self-assembled into doxorubicin-loaded micelles (EKCEK–Dox) in deionized water. TEM and DLS results showed that the EKCEK–Dox micelles were of the regular sphere, with the mean diameter approximately 70 nm. The drug-loading capacity of the prepared micelles was up to 44.6%, and the micelles were very stable in PBS solution. In vitro antitumor experiment showed that the EKCEK–Dox micelles had significant inhibition efficacy on MCF-7 cells, which was much better than the clinical antitumor drug (Doxil®). The IC50 of the EKCEK–Dox micelles (5.6 μg Dox equiv. per mL) was significantly lower than Doxil (8.9 μg Dox equiv. per mL). Therefore, the drug delivery system based on zwitterionic oligopeptides will be a promising strategy for cancer chemotherapy.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Bingjun Sun,Cong Luo,Lin Li,Menglin Wang,Yuqian Du,Donghua Di,Dong Zhang,Guolian Ren,Xiaolei Pan,Qiang Fu,Jin Sun,Zhonggui He
Nanostructured lipid carriers (NLC) have been considered as promising vehicles for oral delivery of taxanes, such as docetaxel (DTX). However, the low drug loading capability (∼5%, w/w) has greatly limited their clinical application. In response to this challenge, a novel lipophilic oleate prodrug of DTX (DTX-OA) was synthesized and efficiently encapsulated in NLC using core-match technology, in which liquid lipid (OA) was used as core matrix to enhance compatibility with DTX-OA. DTX-OA-NLC showed uniform particle size of about 100 nm with markedly high drug loading capability (∼23% of DTX, w/w) compared with DTX-NLC (∼5%, w/w). Besides, DTX-OA-NLC showed better colloidal stability and slower drug release property compared with DTX-NLC. The prepared NLC could be accumulated more easily in MDCK cells than drug solution, and clathrin-mediated endocytosis was the main endocytosis pathway. In situ single-pass intestinal perfusion (SPIP) and intestinal biodistribution studies demonstrated the improved membrane permeability and intestinal wall bioadhesion of NLCs. The bioavailability of DTX-OA-NLC showed 4.04-fold and 2.06-fold higher than DTX solution and DTX-NLC, respectively. These results suggest that the core-matched prodrug-NLC is a promising platform to facilitate the oral delivery of DTX.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2015
·Vol. 11
·期 4
·711-721
·
IF 5.338
Yang Linjie,Jiang Jizong,Hong Jingyi,Di Jing,Liao Yonghong,Kuang Haixue,Wang Xiangtao
The objective of this study was to evaluate the feasibility of producing 10-hydroxycamptothecin nanosuspensions with high drug payload and to then determine the in vitro and in vivo characteristics of these nanosuspensions. Using cholesterol-PEG600 as a stabilizer, 10-hydroxycamptothecin
nanosuspensions were successfully prepared using a precipitation-combined high-pressure homogenization method. A satisfactory drug payload of 90.39% (w/w) was achieved. The obtained nanosuspensions were spherical, with a mean particle size of 115.0 ± 0.4 nm, and they were monodisperse
with a polydispersity index of 0.134 ± 0.001. The 10-hydroxycamptothecin remained in the same crystalline form in both the nanosuspensions and the bulk powder. In vitro, the 10-hydroxycamptothecin nanosuspensions released the encapsulated drug with nearly zero-order kinetics,
and the accumulative release reached 90% within 72 hours. In vitro cytotoxicity assay showed that the 10-hydroxycamptothecin nanosuspensions had significantly enhanced cytotoxicity against HepG2 cells compared to the commercially available 10-hydroxycamptothecin injections. The in
vivo study with H22 tumor-bearing mice and intravenous injection of the drug showed that in contrast to the 10-hydroxycamptothecin injections, the 10-hydroxycamptothecin nanosuspensions exhibited significantly enhanced biodistribution, particularly in the lung (393.40-fold AUC0–24
h, liver (192.35-fold AUC0–24 h, spleen (141.67-fold AUC0–24 h and tumor (64.21-fold AUC0–24 h. The 10-hydroxycamptothecin nanosuspensions also showed improved antitumor therapeutic efficacy over the injections (89.83% vs. 30.56%). This
suggests that cholesterol-PEG600 may be an effective stabilizer for the preparation of hydrophobic drug nanosuspensions and that 10-hydroxycamptothecin nanosuspensions are a promising drug delivery system for tumor treatment.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2010
·
IF 3.151
Yanzhuo Zhang,Tongying Jiang,Qiang Zhang,Siling Wang
Spherical mesocellular foam (MCF) with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. The feasibility of the prepared MCF nanoparticles for oral drug delivery was studied. A model drug, telmisartan (TEL), was loaded onto MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The drug-release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), wide-angle X-ray scattering (WXRS), differential scanning calorimetry (DSC) and HPLC demonstrated the successful incorporation of TEL into the MCF host. It is found that spherical MCF has a high drug loading efficiency up to 42.9% (drug weight/total weight) and higher than that of SBA-15 with a pore diameter of 6.5 nm. It is shown that a fast release rate of TEL was obtained from MCF compared with SBA-15 and pure crystalline TEL using enzyme-free simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement of water-insoluble drugs.
研究领域:
药剂学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS CHEMISTRY AND PHYSICS
·
2020
·
IF 3.408
Chaohui Rao,Min Li,Xiaoqing Sun,Meilin Li,Xiaojie Lian,Huifang Wang,Lan Jia,Baolong Niu,Wenfeng Li
Nano-sized amorphous calcium carbonate (ACC) have a great potential for drug transport and drug delivery because of their high drug loading capacity, excellent biocompatibility and biodegradability. However, ACC is the thermodynamically least stable phase of calcium carbonate, and such thermal metastability often transforms it into more stable vaterite or calcite phases, so the inhibition of the phase transformation of ACC is of great significance for its application in drug delivery systems. Herein, phosphate as a morphology controlling additive was introduced to stabilize the metastable ACC. The results showed that the composite nanoparticles (named here the ACCP) with narrow size distribution located at approximately 128 nm (measured by dynamic light scattering) were obtained, when Ca 2+ concentration and C/P were 10 mM and 7/3 respectively, prepared at 30 °C for 10 min. The powdered X-ray diffraction (XRD) results showed that phosphate has an excellent ability to stabilize ACC, and even after storage for 60 days at room temperature, the structure of ACCP remains amorphous. The in vitro drug release tests showed that ACCP nanoparticles had a high curcumin (Cur) loading capacity and a sustained drug release property. Moreover, the 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH) radical scavenging activity assay showed that ACCP-encapsulating strategy could effectively prevent the decomposition of Cur. In vitro cytotoxicity tests demonstrated that the resultants have excellent biocompatibility. Therefore, the as-prepared ACCP nanoparticles are promising for drug delivery applications.
研究领域:
材料科学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2018
·
IF 2.127
Qian Wang,Xiao Qi Jin,Ji Hong Sun,Shi Yang Bai,Xia Wu,Hamida Panezai
The pH-responsive hollow poly(acrylic acid) (HPAA) microspheres with regulated cavity structure and various shell thicknesses were synthesized. Their structural parameters and textural properties were characterized by various techniques. The ibuprofen loading results indicate the good drug loading capabilities of HPAA microspheres from 13.81 to 17.18%. Their ibuprofen release properties demonstrated their good pH sensitivity and distance-controlled drug diffusion process. Specially, the small-angle X-ray scattering technique was used to suggest the surface roughness and structural irregularities of HPAA before and after drug loading and releasing. These findings clearly indicate the potential of HPAA microspheres to be used as promising candidates in drug delivery.
研究领域:
材料科学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Nanomedicine
·
2019
·
IF 4.717
Wei He,Yawei Du,Wenya Zhou,Chen Yao,Xinsong Li
Aim: A redox-triggered camptothecin (CPT) liposomal system was developed for an improved clinical potential in tumor therapy. Materials & methods: CPT–phosphorylcholine conjugates (CPT–SS–GPCs: CPT–SS–3–GPC and CPT–SS–11–GPC) were synthesized by conjugating CPT to glycerylphosphorylcholine via disulfide bond linker. CPT–SS–GPCs could be assembled into liposomes. Different in vitro and in vivo analyses were used to evaluate the anticancer activities of CPT–SS–GPCs. Results: CPT–SS–GPCs liposomes exhibited extremely high drug loading and uniform size of 150–200 nm. Moreover, the rapid release of parent CPT in reductive condition and high cellular uptake of CPT–SS–GPCs liposomes were observed. At last, in vitro and in vivo anticancer assay showed the enhanced efficacy of CPT–SS–GPCs liposomes. Conclusion: Redox-triggered CPT–SS–GPC liposomes have great potential in tumor therapy.Graphical abstract
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 11
·期 3
·667-674
·
IF 7.571
Zheng Zhang,Weichen Yan,Yuanhui Ji
Cisplatin (CDDP) is one of the most frequently used chemotherapeutic drugs due to its broad-spectrum and potent antitumor activity. Unfortunately, inactivation due to glutathione (GSH) substances and insufficient cellular uptake of CDDP greatly hinder its clinical applications. Herein, manganese dioxide (MnO2) was reported as an efficient glutathione (GSH) consumption material for promoting the accumulation and preventing premature leakage of CDDP in tumor cells. In this work, γ-polyglutamic acid/cisplatin (PGA/CDDP) conjugates and PGA/CDDP nanoparticles (NPs) were respectively constructed via the ligand exchange reaction and electrostatic interaction. Furthermore, PGA/CDDP NPs were in situ coated with MnO2 (PGA/CDDP@MnO2 NPs) through the redox reaction of the residual carboxyl group (–COOH) and potassium permanganate (KMnO4). As a result, the PGA/CDDP@MnO2 NPs achieved a satisfactory drug-loading efficiency (ca. 37.26%) and multi-responsive controlled drug release. Remarkably, the MnO2 shells exhibited excellent performance for efficient glutathione (GSH) consumption and significantly enhanced the killing effect (ca. 2–3 times) in human lung cancer cells (A549) compared with pure CDDP. Moreover, it was observed that PGA/CDDP@MnO2 NPs could also inhibit the migration and invasion of A549 cells. Overall, these remarkable performances of PGA/CDDP@MnO2 NPs make MnO2 promising for controlled drug release and intelligent anticancer therapy.
研究领域:
药学
·
材料科学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2021
·
IF 20.722
Xinyu Zhang,Xiao Duan,Yueying Hu,Zhongmin Tang,Congxiu Miao,Wei Tao,Jun Wu
The clinical applications of polymer-based nanomedicines have been restricted by their complicated synthesis processes, biosafety issues, and uncontrollable drug loading. In this study, we developed a peptide-like polydrug for cancer chemotherapy using the FDA-approved drug melphalan via a simple one-step synthesis strategy. The prepared poly (melphalan) (PMP)-PEG was characterized through standard methods and formulated into sub-100 nm nanoparticles using the nanoprecipitation method. The poly (melphalan)-PEG nanoparticles (PMP NPs) showed controllable drug loading (up to 70 wt%) with high stability in buffers. In vitro cell viability studies showed good cell uptake behavior and high cytotoxicity of the PMP-NPs compared to Evomela controls (a commercial and clinical melphalan formulation). For in vivo mouse models tests, the PMP-NPs could accumulate in the tumor sites for ≥ 1 week and effectively inhibited tumor growth with minimal side-effects. This peptide synthesis strategy and a melphalan based polydrug nanoplatform may be promising for new drug development and effective cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Lingling Wang,Xiuhua Zhao,Fengjian Yang,Weiwei Wu,Mingfang Wu,Yuanyuan Li,Xiaoxue Zhang
In this work, paclitaxel was loaded into porous starch in the form of nanoparticles (PNPS), and the properties of PNPS were investigated by using raw paclitaxel and the system of paclitaxel directly loaded into porous starch (PPS) as control groups. According to the tested results, the drug loading ( DL ) and encapsulation efficiency ( EE ) of PNPS were 14.13% ± 0.27% and 73.92% ± 0.54%, higher than that of PPS (9.79% ± 0.31% and 71.17% ± 0.67%) respectively. Compared with raw paclitaxel and PPS, PNPS exhibited the more prominent dissolution rate and bioavailability, in which the bioavailability of PPS and PNPS were 2.94 and 5.42 times of that of raw paclitaxel respectively. In addition, the IC 50 values of raw paclitaxel, PPS and PNPS on Lewis Lung Carcinoma (LLC) cells were 17,703.41 ± 15.76 μM, 95.10 ± 5.32 μM and 85.68 ± 7.38 μM respectively. Furthermore, the residues of acetone in PPS and PNPS were less than the ICH limit for acetone in class III solvents. To summarize, the preparation of PNPS was a potential method to improve the dissolution and bioavailability of paclitaxel.
研究领域:
药学
·
药物递送系统
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2019
·Vol. 20
·期 2
·1-11
·
IF 2.608
Liu Chunxia,Lin Ling,Huang Zhengwei,Wu Qiaoli,Jiang Junhuang,Lv Li,Yu Xiaoxia,Quan Guilan,Li Guocheng,Wu Chuanbin
Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease associated with the high morbidity and mortality. Long-term intermittent therapy by inhalable antibiotics has recently emerged as an effective approach for NCFB treatment. However, the effective delivery of antibiotics to the lung requires administering a high dose to the site of infection. Herein, we investigated the novel inhalable silk-based microparticles as a promising approach to deliver high-payload ciprofloxacin (CIP) for NCFB therapy. Silk fibroin (SF) was applied to improve drug-payload and deposit efficiency of the dry powder particles. Mannitol was added as a mucokinetic agent. The dry powder inhaler (DPI) formulations of CIP microparticles were evaluated in vitro in terms of the aerodynamic performance, particle size distribution, drug loading, morphology, and their solid state. The optimal formulation (highest drug loading, 80%) exhibited superior aerosolization performance in terms of fine particle fraction (45.04 ± 0.84%), emitted dose (98.10 ± 1.27%), mass median aerodynamic diameter (3.75 ± 0.03 μm), and geometric standard deviation (1.66 ± 0.10). The improved drug loading was due to the electrostatic interactions between the SF and CIP by adsorption, and the superior aerosolization efficiency would be largely attributed to the fluffy and porous cotton-like property and low-density structure of SF. The presented results indicated the novel inhalable silk-based DPI microparticles of CIP could provide a promising strategy for the treatment of NCFB.
研究领域:
药学
·
呼吸医学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2017
·Vol. 19
·期 3
·1141-1151
·
IF 2.451
Chen Jianmin,Huang Weiyue,Huang Ziyao,Liu Shiqi,Ye Yaling,Li Qinglian,Huang Meiping
Dissolving microneedles (MNs) offered a simple, minimally invasive method for meloxicam (MX) delivery to the skin. However, the fabrication of dissolving MNs still faced some challenges, such as significant time consumption, loss of drug activity, and difficulty in regulating MN drug loading. To address these issues, we developed the tip-dissolving (TD) MNs. Several kinds of drugs were encapsulated successfully, and the quantity of MX ranged from 37.23 ± 8.40 to 332.53 ± 13.37 μg was precisely controlled. The effects of fabrication process on biomacromolecules stability were studied, and it was found that tyrosinase kept 90.4% activity during the fabrication process. The whole process for the fabrication of MNs only takes approximately 1 h. In order to further evaluate the potential of the TD MNs, MX TD MNs were prepared for in vitro release experiments, in vivo release experiments, safety evaluation, pharmacokinetic studies, and pharmacodynamic studies. The results demonstrated that MX TD MNs offered several advantages, including rapid release of the encapsulated drug (91.72% within 30 min), efficient drug delivery to skin (79.18%), no obvious skin irritation, decent relative bioavailability (122.3%), and strong anti-inflammatory and analgesic effects. Based on these results, we envisage that the TD MNs have promising potential for transdermal drug delivery of MX.
研究领域:
药学
·
生物医学工程
·
药物递送系统
✓ 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）