PEG300（乙二醇聚乙烯）（聚乙二醇300）是一种分子量为300的中性聚合物，是一种由乙二醇重复单元形成的水溶性、低免疫原性和生物相容性聚合物。
PEG-300, a neutral polymer with a molecular weight of 300, is a water-soluble, low immunogenic and biocompatible polymer formed by repeating units of ethylene glycol [1，2].
Relatively high but clinically achievable PEG-300 levels can inhibit P-gp activity in Caco-2 cell monolayers, thereby enhancing the permeability of anticancer drugs such as paclitaxel and doxorubicin. For example, increasing the concentration of PEG-300 will lead to the increase of Papp and AP to BL of [3H] paclitaxel [P-gp substrate][3-6]12-14,28 and the decrease of Papp and BL to AP. At high concentrations (20%, v/v) of peg-300, it seems that paclitaxel is transported across Caco-2 cell monolayers by simple passive transcellular diffusion. Similar peg induced inhibition of efflux transporters (e.g., P-gp and / or P-gp / MRP activity) was observed in Caco-2 cells, [5] doxorubicin, indicating that PEG induced inhibition of efflux is not a unique phenomenon of paclitaxel.
PEG-300是一种中性聚合物，分子量为300，由乙二醇重复单元形成。它是水溶性、低免疫原性和生物相容性的聚合物。
相对较高但在临床上可达到的PEG-300水平可以抑制Caco-2细胞单层中P-gp活性，从而增强像紫杉醇和多柔比星等抗癌药物的渗透性。例如，增加PEG-300浓度将导致[3H]紫杉醇[P-gp底物]的Papp和AP to BL[3-6]12-14,28增加，并降低Papp和BL to AP。在高浓度（20％v/v）的PEG-300下，似乎紫杉醇通过简单的跨细胞膜扩散被运输穿过Caco-2细胞单层。类似地，在Caco-2细胞中观察到了peg诱导外流转运体（如P-gp和/或P-gp/MRP活性）的抑制作用[5]多柔比星，表明PEG诱导外流阻滞不是紫杉醇独有现象。
参考文献:
[1] Lee C C, Su Y C, Ko T P, et al. Structural basis of polyethylene glycol recognition by antibody[J]. Journal of biomedical science, 2020, 27(1): 1-13.
[2] Billingham J, Breen C, Yarwood J. Adsorption of polyamine, polyacrylic acid and polyethylene glycol on montmorillonite: An in situ study using ATR-FTIR[J]. Vibrational Spectroscopy, 1997, 14(1): 19-34.
[3] Krishna R, Mayer L D. Multidrug resistance (MDR) in cancer: mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs[J]. European Journal of Pharmaceutical Sciences, 2000, 11(4): 265-283.
[4] Van Asperen J, Van Tellingen O, Sparreboom A, et al. Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC 833[J]. British Journal of Cancer, 1997, 76(9): 1181-1183.
[5] van Asperen J, van Tellingen O, van der Valk M A, et al. Enhanced oral absorption and decreased elimination of paclitaxel in mice cotreated with cyclosporin A[J]. Clinical cancer research: an official journal of the American Association for Cancer Research, 1998, 4(10): 2293-2297.
| Cell experiment [1]: | |
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Cell lines |
Caco-2 cells |
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Preparation Method |
When Caco-2 cells were added, 1.5 ml of complete medium was added to the top [apical (AP) compartment] and 2.6 ml to the bottom [basolateral (BL) compartment] of each transwell1. The P-gp activity in these cell monolayers was routinely evaluated by bidirectional transport studies of the P-gp substrate [3H] paclitaxel. |
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Reaction Conditions |
0/20% for 3h |
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Applications |
The AP-to-BL flux of testosterone (0.3 mM) across Caco-2 cell monolayers was determined in the absence and presence of the highest concentration (20%, v/v) of PEG-300 used in these studies to test any possible effects of this excipient on the passive transcellular pathway across Caco2 cells.33 The experimental results suggest that PEG-300 does not alter the passive transcellular pathway across Caco-2 cell monolayers. |
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参考文献: [1]. Hugger E D, Audus K L, Borchardt R T. Effects of poly (ethylene glycol) on efflux transporter activity in Caco?\2 cell monolayers[J]. Journal of pharmaceutical sciences, 2002, 91(9): 1980-1990. |
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