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.
References:
[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.
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。