Pharm Res
(2020) 37:66
Page 13 of 14 66
1
3. Liu T, Yuan X, Jia TT, Liu C, Ni ZH, Qin ZL, et al. Polymeric
prodrug of bufalin for increasing solubility and stability: synthesis
and anticancer study in vitro and in vivo. Int J Pharm. 2016;506(1–
to enhance the antitumor efficacy of TXA9. All of four pro-
drugs could increase the water-solubility of TXA9 dramati-
cally. TPGS-Gly-TXA9 was found with the best stability
in vitro and the longest half-life in vivo among four prodrugs.
Then the improved antitumor efficacy of TPGS-Gly-TXA9
was confirmed on A549 xenograft nude mice compared with
that of TXA9. Although this study had certified the potential
antitumor efficacy of TPGS-Gly-TXA9, the antitumor mech-
anism should be investigated in further research to provide
more evidence for clinical application.
2
):382–93.
14. Cao N, Feng SS. Doxorubicin conjugated to D-alpha-tocopheryl
polyethylene glycol 1000 succinate (TPGS): conjugation chemistry,
characterization, in vitro and in vivo evaluation. Biomaterials.
2
008;29:3856–65.
1
1
1
1
1
5. Bao YL, Guo YY, Zhuang XT, Li D, Cheng BL, Tan SW, et al. D-
α-tocopherol polyethylene glycol succinate-based redox-sensitive
paclitaxel prodrug for overcoming multidrug resistance in cancer
cells. Mol Pharm. 2014;11(9):3196–209.
6. Anbharasi V, Cao N, Feng SS. Doxorubicin conjugated to D-
alpha-tocopheryl polyethylene glycol succinate and folic acid as a
prodrug for targeted chemotherapy. J Biomed Mater Res A.
ACKNOWLEDGMENTS AND DISCLOSURES. This research did
not receive any specific grant from funding agencies in the
public, commercial, or not-for-profit sectors. The authors
state no conflict of interest.
2010;94A(3):730–43.
7. Lu L, Yan Z, Weng S, Zhu W, Qin L. Complete regression of
xenograft tumors using biodegradable mPEG-PLA-SN38 block co-
polymer micelles. J Colloids Surf B Biointerfaces. 2016;142:417–
2
3.
8. Wei Z, Hao J, Yuan S, Li Y, Juan W, Sha X, et al. Paclitaxel-loaded
Pluronic P123/F127 mixed polymeric micelles: formulation, opti-
mization and in vitro characterization. Int J Pharm. 2009;376(1–2):
176–85.
REFERENCES
9. Hu X, Liu RL, Zhang D, Zhang J, Li ZH, Luan YX. Rational
design of an amphiphilic chlorambucil prodrug realizing self-
assembled micelles for efficient anticancer therapy. ACS Biomater
Sci Eng. 2018;4:973–980.
0. Lommerse J P M, Price S L, Taylor R. Hydrogen bonding of
carbonyl, ether, and ester oxygen atoms with alkanol hydroxyl
groups. J Comput Chem. 1997;18(6):757–774.
1. Hao T, Chen D, Liu K, Qi Y, Li Z. Micelles of d-α-tocopheryl
polyethylene glycol 2000 succinate (TPGS 2K) for doxorubicin
delivery with reversal of multidrug resistance. ACS Appl Mater
Interfaces. 2015;7(32):18064–75.
2. Vig BS, Huttunen KM, Laine K, Rautio J. Amino acids as promoi-
eties in prodrug design and development. Adv Drug Deliv Rev.
1
2
.
.
Stewart BW, Wild CP. World Cancer report. International Agency
for Research on Cancer 2014.
Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation
from non-small-cell lung cancer to small-cell lung cancer: molecular
drivers and cells of origin. Lancet Oncol. 2015;16(4):e165–72.
Xue R, Han N, Xia MY, Ye C, Hao ZH, Wang LH, et al. TXA9, a
cardiac glycoside from Streptocaulon juventas , exerts a potent anti-
tumor activity against human non-small cell lung cancer cells
in vitro and in vivo. Steroids. 2015;94(23):51–9.
2
2
3
.
4.
5.
6.
Ye C, Wang H, Xue R, Han N, Wang LH, Yang JY, et al. Minor
cytotoxic cardenolide glycosides from the root of Streptocaulon
juventas. Steroids. 2015;93:39–46.
Greenwald RB, Yun HC, Mcguire J, Conover CD. Effective drug
delivery by PEGylated drug conjugates. Adv Drug Deliv Rev.
2
2
013;65(10):1370–85.
2
3. Pasut G, Veronese FM. Polymer–drug conjugation, recent achieve-
ments and general strategies. Prog Polym Sci. 2007;32(8):933–61.
4. Roy HK, DiBaise JK, Black J, Karolski WJ, Ratashak A, Ansari S.
Polyethylene glycol induces apoptosis in HT-29 cells: potential
mechanism for chemoprevention of colon cancer. FEBS Lett.
2
003;55(2):217–50.
2
Banerjee SS, Aher N, Patil R, Khandare J. Poly(ethylene glycol)-
Prodrug conjugates: concept, design, and applications. J Drug
Deliv. 2012;2012:1–17.
2
001;496(2–3):143–6.
7
8
.
.
Zhang ZP, Tan SW, Feng SS. Vitamin E TPGS as a molecular
biomaterial for drug delivery. Biomaterials. 2012;33(19):4889–906.
Greenwald RB, Gilbert CW, Pendri A, Conover CD, Xia J,
Martinez A. Drug delivery systems: water soluble taxol 2'-poly(eth-
ylene glycol) ester prodrugs-design and in vivo effectiveness. J Med
Chem. 1996;39(2):424–31.
Sun HP, Zhang Q, Zhang Z, Tong J, Chu DF, Gu JK.
Simultaneous quantitative analysis of Polyethylene Glycol (PEG),
PEGylated paclitaxel and paclitaxel in rats by MS/MSALL tech-
nique with hybrid quadrupole time-of-flight mass spectrometry. J
Pharm Biomed Anal. 2017;145:255–61.
2
5. Veronese FM, Schiavon O, Pasut G, Mendichi R, Andersson L,
Tsirk A, et al. PEG-doxorubicin conjugates:influence of polymer
structure on drug release,in vitro cytotoxicity,biodistribution,and
antitumor activity. Bioconjug Chem. 2005;16(4):775–84.
26. Lu B, Huang D, Zheng H, Huang ZJ, Xu PH, Xu HX, et al.
Preparation, characterization, and in vitro efficacy of O-
carboxymethyl chitosan conjugate of melphalan. Carbohydr
Polym. 2013;98(1):36–42.
27. Sun JJ, Liu YH, Chen YC, Zhao WC, Zhai QY, Rathod S, et al.
Doxorubicin delivered by a redox-responsive dasatinib-containing
polymeric prodrug carrier for combination therapy. J Control
Release. 2017;258:43–55.
28. Sun X, Guowei W, Hao Z, Shiqi H, Xin L, Jianbin T, et al. The
blood clearance kinetics and pathway of polymeric micelles in can-
cer drug delivery. ACS Nano. 12:6179–92.
29. Li M, Liang Z, Sun X, Gong T, Zhang Z. A polymeric prodrug of
5-fluorouracil-1-acetic acid using a multi-hydroxyl polyethylene
glycol derivative as the drug carrier. PLoS One. 2014;9(11):
e112888.
9
.
1
1
1
0. Ding Y, Zhang P, Tang XY, Zhang C, Ding S, Ye H, et al. PEG
prodrug of gambogic acid: amino acid and dipeptide spacer effects.
Polymer. 2012;53(8):1694–702.
1. Zhao YJ, Wei W, Su ZG, Ma GH. Poly (ethylene glycol) prodrug
for anthracyclines via N-Mannich base linker: design, synthesis and
biological evaluation. Int J Pharm. 2009;379(1):90–9.
2. Rowinsky EK, Rizzo J, Ochoa L, Takimoto CH, Forouzesh B,
Schwartz G, et al. A phase I and pharmacokinetic study of pegylated
camptothecin as a 1-hour infusion every 3 weeks in patients with
advanced solid malignancies. J Clin Oncol. 2003;21(1):148–57.
30. Luo C, Sun J, Liu D, Sun BJ, Lei M, Musetti S, et al. Self-assembled
redox dual-responsive prodrug-nanosystem formed by single