CHINESE JOURNAL OF CHEMISTRY
·
2020
·Vol. 38
·期 7
·690-696
·
IF 3.826
Jiali Sun,Qi Wei,Na Shen,Zhaohui Tang,Xuesi Chen
Summary of main observation and conclusion Physical encapsulation of drugs into polymer micelles is a common method of loading hydrophobic drugs. Methoxy polyethylene glycol-poly( D , L -lactide) (mPEG-PDLLA) is one of the most commonly used drug carrier. At present, whether a carrier is suitable for the loading of a certain drug is determined by drug loading experiments. This process costs a lot of time. Therefore, an efficient predicting method to avoid time-consuming tests is critical. In this study, we prepared mPEG 5k -PDLLA 5k and used it to load a series of drugs. Three parameters were used to test the miscibility of mPEG 5k -PDLLA 5k with drugs, including absolute difference in Hildebrand solubility parameters (|Δ δ |), Flory–Huggins interaction parameter ( χ ) and the distance ( D value) calculated from the two-dimensional solubility parameters. We found the two-dimensional solubility parameters obtained from JB2013 group contribution (GC) method was useful. By comparing the drug loading content (DLC) with the D value, we found that when the D value was less than 5.0 (MJ/m 3 ) 1/2 , the miscibility of drug and mPEG 5k -PDLLA 5k was good and drug loading capability was high; when the D value was more than 8.0 (MJ/m 3 ) 1/2 , the drug was barely loaded. Thus, this work provided a rationale to qualitatively predict the loading capability of mPEG 5k -PDLLA 5k for hydrophobic drugs.
研究领域:
药剂学
·
生物医学工程
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产品关联
DOI
高影响因子
Theranostics
·
2017
·
IF 8.766
Liwei Tan,Jinrong Peng,Qian Zhao,Lan Zhang,Xichuan Tang,Lijuan Chen,Minyi Lei,Zhiyong Qian
Satisfactory drug loading capacity and stability are the two main factors that determine the anti-cancer performance. In general, the stability of the micelles is reduced when the drug loading (DL) is increased. Therefore, it was a challenge to have high drug loading capacity and good stability. In this study, we introduced a hydrophilic poly (L-Lysine) (PLL) segment with different molecular-weights into the monomethoxy poly (ethylene glycol)-poly (D, L-lactide) (MPEG-PDLLA) block copolymer to obtain a series of novel triblock MPEG-PDLLA-PLL copolymers. We found that the micelles formed by a specific MPEG 2k -PDLLA 4k -PLL 1k copolymer could encapsulate docetaxel (DTX) with a satisfactory loading capacity of up to 20% (w/w) via the thin film hydration method, while the stability of drug loaded micellar formulation was still as good as that of micelles formed by MPEG 2k -PDLLA 1.7k with drug loading of 5% (w/w). The results from computer simulation study showed that compared with MPEG 2k -PDLLA 1.7k , the molecular chain of MPEG 2k -PDLLA 4k -PLL 1k could form a more compact funnel-shaped structure when interacted with DTX. This structure favored keeping DTX encapsulated in the copolymer molecules, which improved the DL and stability of the nano-formulations. The in vitro and in vivo evaluation showed that the DTX loaded MPEG 2k -PDLLA 4k -PLL 1k (DTX/MPEG 2k -PDLLA 4k -PLL 1k ) micelles exhibited more efficiency in tumor cell growth inhibition. In conclusion, the MPEG 2k -PDLLA 4k -PLL 1k micelles were much more suitable than MPEG 2k -PDLLA 1.7k for DTX delivery, and then the novel nano-formulations showed better anti-tumor efficacy in breast cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2019
·Vol. 14
·期 6
·065007
·
IF 3.44
Ruifang Zhao,Zunkai Xu,Bing Li,Tao Chen,Naibin Mei,Chuang Wang,Zongbao Zhou,Lingling You,Chaoxi Wu,Xiaoying Wang,Shunqing Tang
The development of degradable polymer scaffolds is a key issue in bone regeneration. Poly(D, L-lactide) (PDLLA) and its derivatives have usually been applied to the construction of degradable scaffolds, but these scaffolds had problems with acidic degradation products and quick loss of mechanic strength during the later degradation, which usually led to scaffold collapse and cavity formation because of the slower rate of bone regeneration. In the present paper, a polysaccharide derivative, agarose acetate (AGA), was synthesized and a novel porous AGA scaffold was successfully developed through a salt-leaching process. The AGA scaffold had over 90% porosity without swelling in water, and compared to collapse and acidic products of PDLLA scaffold during degradation, the AGA scaffold maintained a stable morphology and a nearly neutral pH value over 18 months' degradation in PBS. A bone mesenchymal stem cells (BMSCs) adhesion and proliferation experiment showed that more cells adhered to the AGA scaffold than to the PDLLA scaffold. A subcutaneous implant test showed that the AGA scaffold slowly degraded and did not cause an inflammatory response surrounding the implantation lesion site. AGA scaffold was implanted into femur defects in New Zealand white rabbits to test its in vivo performance. Results indicated that the AGA scaffold accelerated the process of bone regeneration compared to the PDLLA group and, with time, new bone was formed from the margin toward the center of the scaffolds, and the scaffold left in place retained its porous structure without collapsing. Meanwhile, the AGA scaffold showed a low degradation rate and kept its shape during the in vivo degradation compared to the PDLLA scaffold. This performance could have the benefit of integrated regenerative bone being formed instead of cavities due to the quickly degraded scaffold disappearing. These results demonstrate that the AGA scaffold has significant potential in bone regeneration applications.
研究领域:
组织工程
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生物医用材料
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骨科
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 17
·13698-13709
·
IF 3.289
Ying Hao,YiXing Huang,YunQi He,JinRong Peng,LiJuan Chen,Xun Hu,ZhiYong Qian
In this study, we successfully prepared MPEG–PDLLA polymer micelles with two different particle sizes, A and B. DLS and TEM assays demonstrated that the particle sizes of the polymer micelles A and polymer micelles B were about 25 nm and 150 nm respectively. The stability of the MPEG–PDLLA polymer micelles in vitro revealed that the free Cy5.5 dye had been successfully loaded into the polymer micelles as a fluorescence marker and the fluorescence wasn’t quenched until 72 h. The cellular uptake of the polymer micelles was time-dependent and micelles A (particle size 25 nm) showed a higher efficiency to be internalized into the cytoplasm of MCF-7 cells than micelles B (particle size 150 nm). Furthermore, in vivo and in vitro biodistribution and tumor-targeting of polymer micelles MPEG–PDLLA were investigated in female MCF-7 tumor-bearing balb/cA-nu mice with an IVIS imaging system. The results showed that polymer micelles A (particle size 25 nm) had a time dependent biodistribution and tumor site accumulation in mice bearing MCF-7 tumors. Meanwhile, the NIR fluorescence intensity of polymer micelles B (particle size 150 nm) in tumor sites showed a pattern of a rise, a peak and then a decline. What’s more, the distribution of the polymer micelles in the tissue slices demonstrated the same results. Consequently, the results indicated that the micelles with a smaller particle size (25 nm) could be more efficiently internalized into cells and increase the enhanced permeation and retention (EPR) effect in tumor tissue. Therefore, a reasonable small size of micelles may be a key factor for a high-performance anti-cancer drug delivery system.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 7
·1-13
·
IF 4.026
Cao Xia,He Qing,Adu-Frimpong Michael,Shen Xinyi,Rong Wanjing,Li Xiaoxiao,Zhang Jian,Xia Xiaoli,Shi Feng,Ji Hao,Toreniyazov Elmurat,Wang Qilong,Yu Jiangnan,Xu Ximing
Pinocembrin (PCB) is 5,7-dihydroxyl flavanone and has multiple pharmacological activities, namely, anti-inflammation, anti-osteoporotic, and so on. However, low water solubility and bioavailability have hindered its application. Herein, we aimed to increase its bioavailability through preparation of F127/MPEG-PDLLA polymer micelles (PCB-M). We characterized the micelles through appropriate attributes such as analysis of particle size (PS), polydispersity (PDI), transmission electron microscopic (TEM) image, stability test, and evaluation of in vitro release of drug. After physical characterization, the respective PS, PDI, and entrapment efficiency (EE) of PCB-M were estimated to be 27.63 ± 0.17 nm, 0.055 ± 0.02, and 90.53 ± 0.01%. Fluorescence probe method was employed to measure critical micelle concentration (CMC) of PCB-M, we observed CMC was low, thereby suggesting that PCB-M had good stability. In vitro release analysis indicated that the rate of cumulative PCB release from PCB-M was greater than 90% in each medium compared with free PCB, which was less than 40%, thus pointing to a significantly improved solubility of PCB. In vivo pharmacokinetic results showed that oral biological availability of PCB-M increased 5.3 folds comparable to free PCB. The effects of PCB on osteoblasts and ALP activities were investigated; subsequently, zebrafish osteoporotic model was established with prednisolone to study the anti-osteoporotic effects of PCB and PCB-M. The results showed that PCB improved osteoporosis with PCB-M being more effective than free PCB. Finally, PCB-M can be used as a promising method to improve the solubility of PCB, while the bioavailability and anti-osteoporotic effect of PCB could be improved, thus laying a foundation for clinical use in the future. Graphical Abstract
研究领域:
药学
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药理学
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材料科学
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生物医学工程
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骨骼研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Fengying Dai,Xinpo Li,Kepeng Lv,Jing Wang,Yiping Zhao
Nanomedicine faces the challenges of infinite dilution, shear force, biological protein, or electrolyte competition. However, core cross-linking leads to biodegradability deficiency and brings inevitable side effects of nanomedicine on normal tissues. In order to overcome this bottleneck problem, we turn to amorphous poly(d,l)lactic acid (PDLLA)-dextran bottlebrush to emphasize the core stability of nanoparticles, and the amorphous structure offers an additional advantage of fast degradation property over the crystalline PLLA polymer. The graft density and side chain length of amorphous PDLLA together played important influence roles in controlling the architecture of nanoparticles. This effort produces structure-abundant particles, including micelles, vesicles, and large compound vesicles after self-assembly. Here, the amorphous bottlebrush PDLLA was verified to play a beneficial role in the structure stability and degradability of nanomedicines. The codelivery of the hydrophilic antioxidant of citric acid (CA), vitamin C (VC), and gallic acid (GA) via the optimum nanomedicines could effectively repair the SH-SY5Y cell damage caused by H2O2. The CA/VC/GA combination treatment repaired the neuronal function efficiently, and the cognitive abilities of senescence-accelerated mouse prone 8 (SAMP8) recovered.
研究领域:
纳米医学
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聚合物化学
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神经科学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 12
·6373-6380
·
IF 2.936
Bingbing Wang,Hongming Lou,Hongli Xu,Junpeng Zhao,Qiujun Wang,Qiao Shi,Yonghong Deng
In this work, a novel star-comb copolymer based on poly(d,L-lactide) (PDLLA) macromonomer and poly(ethylene glycol)methyl ether methacrylate (PEGMA) was prepared, and the electrochemical properties were studied, with the aim of using it as a solid polymer electrolyte in lithium ion batteries. The six-arm vinyl functionalized PDLLA macromonomer was synthesized by a ring-opening polymerization (ROP) of D,L-lactide and subsequently an acylation of the hydroxy end-groups. A series of free-standing solid polymer electrolyte membranes from different ratios of PDLLA, PEGMA and LiTFSI were prepared through solvent-free free radical polymerization under UV radiation. The chemical structure of the obtained polymers was confirmed by 1H NMR and FTIR. The as-prepared six-arm star-comb solid polymer electrolytes (PDLLA-SPEs) exhibit good thermal stability with Td5%s of ∼270 °C and low Tgs of −48 to −34 °C. The electrochemical characterization shows that the PDLLA-SPEs possess a wide electrochemical window up to 5.1 V with an optimal ionic conductivity of 9.7 × 10−5 S cm−1 at 60 °C at an EO/Li+ ratio of 16 : 1. Furthermore, the all-solid-state LiFePO4/Li cells display extraordinary cycling and rate performances at 60 °C by curing the PDLLA-SPEs directly on the cathode. These superior properties of the six-arm star-comb PDLLA-SPE make it a promising candidate solid electrolyte for lithium batteries.
研究领域:
材料科学
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电化学
·
能源存储
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Xiaoli Xia,Jian Zhang,Michael Adu‑Frimpong,Xiaoxiao Li,Xinyi Shen,Qing He,Wanjing Rong,Hao Ji,Elmurat Toreniyazov,Ximing Xu,Jiangnan Yu,Qilong Wang
Hyperoside (Hyp) self-assembled polymeric micelles (Hyp-PMs) were purposely developed to enhance aqueous solubility, in vivo availability and anti-oxidative effect of Hyp. In preparing Hyp-PMs, we employed the thin film dispersion method with the micelles consisting of TPGs and mPEG2000-PDLLA3000. The particle size, polydispersity index and zeta potential of Hyp-PMs were 67.42 ± 1.44 nm, 0.229 ± 0.015 and −18.67 ± 0.576 mV, respectively, coupled with high encapsulation efficiency （EE）of 90.63 ± 1.45% and drug loading (DL) of 6.97 ± 1.56%. Furthermore, the value of critical micelle concentration (CMC) was quite low, which indicated good stability and improved self-assembly ability of Hyp-PMs. Also, trend of in vitro Hyp release from Hyp-PMs demonstrated enhanced solubility of Hyp. Similarly, in comparison with free Hyp, oral bioavailability of Hyp-PMs was improved (about 8 folds) whilst half-life of Hyp-PMs was extended (about 3 folds). In vitro anti-oxidative effect showed obvious strong scavenging DPPH capability of Hyp-PMs, which may be attributed to its smaller size and better solubility. Altogether, Hyp-PMs may serve as a possible strategy to potentially enhance aqueous solubility, bioavailability and anti-oxidative effect of Hyp, which may play a key role in Hyp application in the pharmaceutical industries.
研究领域:
药学
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纳米技术
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药物递送系统
·
药代动力学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2017
·
IF 3.234
Ying Hao,Jinrong Peng,Yaguang Zhang,Lijuan Chen,Feng Luo,Cheng Wang,Zhiyong Qian
Breast cancer has been the first killer among women. In this study, combretastatin A-4 (CA-4) loaded 5-amino acid peptide Ala-Pro-Arg-Pro-Gly (APRPG) modified PEG-PDLLA mixed micelles was developed to target tumor neovasculature for breast cancer therapy. CA-4 is an effective vascular disrupting agent. The APRPG-modified PEG-PDLLA polymer was successfully synthesized and thin-film hydration method was used to prepare APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles. Drug loading capacity (DL), encapsulation efficiency (EE), and the optimized ratio of APRPG-PEG-PDLLA: MPEG-PDLLA for efficient drug loading was investigated. The particle size, zeta potential, morphology, and the crystallographic study were carried out to characterize the micelles. In vitro release study revealed a sustained release of CA-4 from the mixed micelles while compared to free CA-4. Moreover, the cytotoxicity data of blank and drug loaded mixed micelles suggested that the APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles were safe drug carriers and the encapsulated CA-4 remained potent antitumor effect. The cellular uptake study and the in vivo imaging and biodistribution study demonstrated that the APRPG peptide modified mixed micelles has the higher cellular uptake efficiency and could significantly facilitate the accumulation at tumor site. Furthermore, the micelles were slowly extravasated from blood vessels and inhibited embryonic angiogenesis in the transgenic zebrafish model. Consequently, the CA-4 loaded APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles group demonstrated a significant inhibition of tumor growth in 4T1 breast cancer model. In short, the CA-4 loaded APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles might have great potential for breast cancer therapy.
研究领域:
肿瘤学
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药剂学
·
生物医学工程
✓ 已验证
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2014
·Vol. 131
·期 12
·
IF 1.64
Wenliang Li,Wenjing Zhang,Xiuyun Yang,Zhigang Xie,Xiabin Jing
A series of four-arm star block copolymers poly(ethylene glycol)-block-poly( d,l -lactide) (PEG-PDLLA) with different hydrophobic length were synthesized by ring-opening polymerization of lactide and characterized using 1 H NMR and gel permeation chromatography (GPC). These copolymers could self-assemble in aqueous solution to form the vesicle structure with controlled size and morphologies. Transmission electron microscopy (TEM) and DLS show the polymersomes are spherical with diameter of 70∼500 nm. The polymersomes made by direct hydration of copolymer thin films in water exhibit the controllable ability of encapsulating hemoglobin under mild condition. The hemoglobin content in the polymersomes could reach to 35 wt %. More importantly, the encapsulated hemoglobin keeps its own bioactivity and is capable of binding oxygen. This hemoglobin-encapsulated four-arm PEG-PLA polymersomes could have the potential to be applied as an artificial oxygen carrier for transfusion. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40433.
研究领域:
生物材料
·
医学工程
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产品关联
DOI
高影响因子
RAPID PROTOTYPING JOURNAL
·
2020
·Vol. 26
·期 6
·1131-1143
·
IF 3.099
Kesheng Lin,Jie Liu,Jia-Min Wu,Yunlong Sun,Feng Li,Yan Zhou,Yusheng Shi
Purpose The main cause of aseptic inflammation after an in vivo implantation is that Poly(L-lactide) (PLLA) and Poly(D-lactide) have a slower degradation and absorption rate, while Poly(D, L-lactide) (PDLLA) has a much faster degradation rate than PLLA because of its amorphous structure. Also, the hydrolyzate of Hydroxyapatite (HA) is alkaline, which can neutralize local tissue peracid caused by hydrolysis of Polylactic acid. Design/methodology/approach In this study, the selective laser sintering (SLS) technique was chosen to prepare bone scaffolds using nano-HA/PDLLA composite microspheres, which were prepared by the solid-in-oil-in-water (S/O/W) method. First, the SLS parameters range of bulk was determined by the result of a single-layer experiment and the optimized parameters were then obtained by the orthogonal experiment. The tensile property, hydrophobicity, biocompatibility, biological toxicity and in vitro degradation of the samples with optimized SLS parameters were characterized. Findings As a result, the samples showed a lower tensile strength because of the many holes in their interior, which was conducive to better cell adhesion and nutrient transport. In addition, the samples retained their inherent properties after SLS and the hydrophobicity was improved after adding nano-HA because of the OH group. Furthermore, the samples showed good biocompatibility with the large number of cells adhering to the material through pseudopods and there was no significant difference between the pure PDLLA and 10% HA/PDLLA in terms of biological toxicity. Finally, the degradation rate of the composites could be tailored by the amount of nano-HA. Originality/value This study combined the S/O/W and SLS technique and provides a theoretical future basis for the preparation of drug-loaded microsphere scaffolds through SLS using HA/PDLLA composites.
研究领域:
材料科学
·
生物医学工程
·
组织工程
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Ying Qu,BeiYu Wang,BingYang Chu,ChenLu Liu,Xin Rong,Hua Chen,JinRong Peng,ZhiYong Qian
Spinal fusion is the classic treatment to achieve spinal stability for the treatment of the spinal disease. Generally, spinal fusion still has to combine a certain of bone matrix for promoting bone formation to achieve the desired fusion effect based on the surgery, including the traditional bone matrix, such as the autologous bone, allografts and xenografts. Nevertheless, some problems still existed such as the immunogenic problems, the secondary wound, and pathogenic transfer and so on. Here the injectable thermosensitive hydrogel could substitute to avoid the problems as a potential biological scaffold for tissue engineering. Once injected, they could fill in the irregular-shaped cavity and change to a gel state at physiological temperature. We wanted to design the collagen/n-HA/BMP-2@PCEC/PECE hydrogel composites based on previous work about collagen/n-HA/PECE hydrogel to exhibit better performance in guiding spinal fusion because of the addition of BMP-2@PCEC nanoparticles (PCEC, PCL-PEG-PCL). However, when the hydrogels were injected, one of the surfaces was in contact with the spine, but others were in contact with soft tissue like muscles and fascia. The release behavior was the same at the different surfaces, so the factors could be released into the soft tissue, and it may then be consumed or lead to ectopic bone formation. The hydrogel composites should be improved to adjust the direction of the releaser behavior. In consequence, we wrapped an electrostatic spinning nanofiber membrane possessing hydrophobicity around the hydrogels. In this study, we developed a system that the collagen/n-HA/BMP-2@PCEC/PECE hydrogels were wrapped with the hydrophobicity PDLLA electrospun nanofiber membrane, setting up a barrier between the hydrogels and the soft tissue. The system could exhibit biocompatibility, preventing the factors from escaping to keep their retention in the needed places of osteogenesis; the results demonstrated that it showed an excellent effect on spinal fusion.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）