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
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
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生物医学工程
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产品关联
DOI
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
·
骨骼研究
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产品关联
DOI
PubMed
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
·
纳米技术
·
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
·
药剂学
·
生物医学工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）