Pluronic F-127: An Efficient Delivery Vehicle for 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH or Photochlor).

Pluronic F-127: An Efficient Delivery Vehicle for 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH or Photochlor).
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DOI:
10.1111/php.13183
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发表时间:
2020-05
影响因子:
3.3
通讯作者:
Pandey, Ravindra K.
Pandey, Ravindra K.
中科院分区:
生物学3区
文献类型:
--
作者:
Cacaccio, Joseph;Durrani, Farukh;Cheruku, Ravindra R.;Borah, Ballav;Ethirajan, Manivannan;Tabaczynski, Walter;Pera, Paula;Missert, Joseph R.;Pandey, Ravindra K.

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为了确定递送载体对HPPH的光敏功效的影响,将疏水性光敏剂溶解在各种制剂中:在0.5%、1%和2%磷酸盐缓冲溶液(PBS)中的1%吐温80/5%右旋糖、普朗尼克P-123和普朗尼克F-127。HPPH还与Pluronic F-127偶联,并将所得偶联物(PL-20)配制在PBS中。在不同的递送载体中,仅Pluronic P-123显示出显著的载体细胞毒性,而Pluronic F127是无毒的。与PL-20相比,在吐温80和普朗尼克F-127中配制的HPPH显示出更高的细胞摄取,但与PL-20相比,在Colon 26细胞中的长期保留较低。PL-20的更高保留类似地在携带Ct 26肿瘤的BALB/c小鼠体内摄取期间观察到。与体外摄取实验相反,PL-20显示出比在Tween或Pluronic-F127中配制的HPPH略高的摄取。在HPPH Pluronic制剂和PL-20之间也观察到药代动力学特征的显著差异。在相似的体内治疗参数下(药物剂量0.47 µmol/kg,光剂量:注射PS后24小时为135 J/cm 2),在Tween或Pluronic F-127制剂中配制的HPPH显示出相似的体内PDT功效(第60天肿瘤治愈率为20-30%),而PL-20显示出40%的肿瘤治愈率(第60天)。为了研究递送载体在HPPH-PDT中的影响,将HPPH配制在吐温80、普朗尼克F-123、普朗尼克F-127中,并且还与氨基-普朗尼克F-127(PL-20)缀合。在所有制剂中,其中两个HPPH分子与在PBS中配制的氨基-普朗尼克F-127缀合的PL-20在携带Ct 26肿瘤的BALB/c小鼠中的长期肿瘤治愈中显示出更高的肿瘤特异性。
To determine the impact of delivery vehicles in photosensitizing efficacy of HPPH, a hydrophobic photosensitizer was dissolved in various formulations: 1% Tween 80/5% dextrose, Pluronic P-123 and Pluronic F-127 in 0.5, 1 and 2% phosphate buffer solutions (PBS). HPPH was also conjugated to Pluronic F-127 and the resulting conjugate (PL-20) was formulated in PBS. Among the different delivery vehicles, only Pluronic P-123 displayed significant vehicle cytotoxicity whereas Pluronic F127 was non-toxic. Compared to PL-20, HPPH formulated in Tween80 and Pluronic F-127 showed higher cell-uptake, but lower long term retention in Colon26 cell compared to PL-20. The higher retention of PL-20 was similarly observed during in vivo uptake with BALB/c mice baring Ct26 tumors. In contrast to the in vitro uptake experiments, PL-20 showed slightly higher uptake compared to HPPH formulated in Tween or Pluronic-F127. A significant difference in pharmacokinetic profile was also observed between the HPPHPluronic formulation and PL-20. Under similar in vivo treatment parameters (drug dose 0.47 µmol/kg, light dose: 135 J/cm2 at 24 h post-injection of PS), HPPH formulated either in Tween or Pluronic F-127 formulation showed similar in vivo PDT efficacy (20–30% tumor cure on day 60), whereas PL-20 showed 40% tumor cure (day 60). To investigate the impact of delivery vehicles in HPPH-PDT, HPPH was formulated in Tween80, Pluronic F-123, Pluronic F-127 and also conjugated with amino-Pluronic F-127 (PL-20). Among all the formulations, PL-20 in which two molecules of HPPH were conjugated with amino-Pluronic F-127 formulated in PBS showed higher tumor-specificity at long-term tumor cure in BALB/c mice bearing Ct26 tumors.
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