Preparation, Characterization and Pharmacokinetic Study of Arginine Deiminase Lipid Nanoparticles

ZHONG Cai-ling, FENG Jiao, LIU Yu-ying, YANG Qiang, ZHANG Jing-qing

Abstract

To prepare and characterize D-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) modified arginine deiminase (ADI) sulfobutyl-β-Cyclodextrin liposome nanoparticles (ATCL), and to investigate the pharmacokinetic characteristics of ATCL in animals.  Methods  The reverse evaporation method was used to prepare ATCL, and the particle size and Zeta potential of ATCL were measured. Thiosemicarbazone-diacetylmonooxime colorimetric method was used to measure the activity of ADI. After intravenous administration, blood was drawn at set intervals of time and the enzyme activity in the plasma was measured. Enzyme activity-time curve was drawn subsequently and Debris Assessment Software (DAS) 2.1.1 was used to analyze the pharmacokinetic characteristics.  Results  The particle size and the potential of ATCL were (216.1±13.6) nm and (−19.4±2.1) mV, respectively. The optimal temperature and optimal pH for the catalytic reaction of ADI and ATCL were the same, both being 37 ℃ and pH6.5. Results of the analysis showed that the AUC(0-168 h), MRT(0-168 h), Cmax, Tmax, and t1/2 of ATCL were 3.99, 2.56, 1.58, 3.2, and 9.88 times those of free ADI, respectively. Compared with ADI, the bioavailability of ATCL increased by 298.54%.  Conclusion  ATCL prepared in the study can effectively improve the enzyme activity and bioavailability of ADI in Sprague-Dawley rats.

 

Keywords: Arginine deiminase, Liposome nanoparticles, Enzyme activity, Pharmacokinetics, Bioequivalence

 

Full Text:

PDF


References


XING L， TENG J L， BOTELHO M G， et al. Arginine metabolism in bacterial pathogenesis and cancer therapy. Int J Mol Sci，2016，17(3): 363[2021-05-25]. https://doi.org/10.3390/ijms17030363.

FUNG M K L， CHAN G C. Drug-induced amino acid deprivation as strategy for cancer therapy. J Hematol Oncol，2017，10(1): 144[2021-05-25]. https://doi.org/10.1186/s13045-017-0509-9.

ZHANG Y， CHUNG S F， TAM S Y， et al. Arginine deprivation as a strategy for cancer therapy: An insight into drug design and drug combination. Cancer Lett，2021，502: 58–70.

ABOU-ALFA G K， QIN S， RYOO B Y， et al. Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma. Ann Oncol，2018，29(6): 1402–1408.

HAN R Z， XU G C， DONG J J， et al. Arginine deiminase: Recent advances in discovery, crystal structure, and protein engineering for improved properties as an anti-tumor drug. Appl Microbiol Biotechnol， 2016，100(11): 4747–4760.

CHEN G， YANG J， SCHWANEBRG U， et al. Rational surface engineering of an arginine deiminase (an antitumor enzyme) for increased PEGylation efficiency. Biotechnol Bioeng，2019，116(9): 2156–2166.

药，2020，51(6): 1412–1426.

CHUNG S F， KIM C F， KWOK S Y， et al. Mono-PEGylation of a thermostable arginine-depleting enzyme for the treatment of lung cancer. Int J Mol Sci，2020，21(12): 4234[2021-05-25]. https://doi.org/10.3390/ijms21124234.

ZENG T， ZHANG Y， YAN Q， et al. Construction and in vitro evaluation of enzyme nanoreactors based on carboxymethyl chitosan for arginine deprivation in cancer therapy. Carbohydr Polym，2017，162: 35–41.

NEOPHYTOU C M， MESARITIS A， GREGORIOU G， et al. d-a-Tocopheryl Polyethylene Glycol 1000 Succinate and a small-molecule Survivin suppressant synergistically induce apoptosis in SKBR3 breast cancer cells. Sci Rep，2019，9(1): 14375[2021-05-25]. https://doi.org/10. 1038/s41598-019-50884-9.

YOUK H J， LEE E， CHOI M K， et al. Enhanced anticancer efficacy of alpha-tocopheryl succinate by conjugation with polyethylene glycol. J Control Release，2005，107(1): 43–52.

CHENG B， PAN H， LIU D， et al. Functionalization of nanodiamond with vitamin E TPGS to facilitate oral absorption of curcumin. Int J Pharm，2018，540(1/2): 162–170.

SOMANI R R， CHASKAR P K. Arginine deiminase enzyme evolving as a potential antitumor agent. Mini Rev Med Chem，2018，18(4): 363–368.

BELLUATI A， CRACIUN I， LIU J， et al. Nanoscale enzymatic compartments in tandem support cascade reactions in vitro. Biomacromolecules，2018，19(10): 4023–4033.

MEYER C E， CRACIUN I， SCHOENENBERGER C A， et al. Catalytic polymersomes to produce strong and long-lasting bioluminescence. Nanoscale，2021，13(1): 66–70.

MUTLU-AGARDAN N B， HAN S. In vitro and in vivo evaluations on nanoparticle and phospholipid hybrid nanoparticles with absorption enhancers for oral insulin delivery. Pharm Dev Technol，2021，26(2): 157–166.

HUANG Y， GU J， YAN Z， et al. Cytomembrane-mimicking nanocarriers with a scaffold consisting of a CD44-targeted endogenous component for effective asparaginase supramolecule delivery. Nanoscale， 2020，12(22): 12083–12097.

LIN E Y， CHEN Y S， LI Y S， et al. Liposome consolidated with cyclodextrin provides prolonged drug retention resulting in increased drug bioavailability in brain. Int J Mol Sci，2020，21(12): 4408.

YANG L， ZHANG Y， XIE J， et al. Biomimetic polysaccharide-cloaked lipidic nanovesicles/microassemblies for improving the enzymatic activity and prolonging the action time for hyperuricemia treatment. Nanoscale， 2020，12(28): 15222–15235.

HU C， LIANG K， AN R， et al. The characterization, pharmacokinetic, and tissue distribution studies of TPGS-modified artesunate liposome in rats. Drug Dev Ind Pharm，2018，44(9): 1528–1535.

ZHANG Z， TAN S， FENG S S. Vitamin E TPGS as a molecular biomaterial for drug delivery. Biomaterials，2012，33(19): 4889–4906.

LI Y， TAN X， LIU X， et al. Enhanced anticancer effect of doxorubicin by TPGS-coated liposomes with Bcl-2 siRNA-corona for dual suppression of drug resistance. Asian J Pharm Sci，2020，15(5): 646–660.

VIJAYAKUMAR M R， VAJANTHRI K Y， BALAVIGNESWARAN C K， et al. Pharmacokinetics, biodistribution, in vitro cytotoxicity and biocompatibility of Vitamin E TPGS coated trans resveratrol liposomes. Colloids Surf B Biointerfaces，2016，145: 479–491.


Refbacks

  • There are currently no refbacks.