Oligo(Lactic Acid)8-Rapamycin Prodrug-Loaded Poly(Ethylene Glycol)-block-Poly(Lactic Acid) Micelles for Injection
| العنوان: | Oligo(Lactic Acid)8-Rapamycin Prodrug-Loaded Poly(Ethylene Glycol)-block-Poly(Lactic Acid) Micelles for Injection |
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| المؤلفون: | Yu Tong Tam, Zhi-Xiong Ma, John B. Feltenberger, Glen S. Kwon, Lauren Repp |
| المصدر: | Pharmaceutical Research. 36 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Pharmaceutical Science, macromolecular substances, 02 engineering and technology, 030226 pharmacology & pharmacy, Micelle, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Copolymer, Pharmacology (medical), Pharmacology, Aqueous solution, fungi, Organic Chemistry, technology, industry, and agriculture, Prodrug, 021001 nanoscience & nanotechnology, In vitro, Lactic acid, body regions, chemistry, Molecular Medicine, sense organs, 0210 nano-technology, Ethylene glycol, Biotechnology, Nuclear chemistry |
| الوصف: | To prepare an oligo(lactic acid)8-rapamycin prodrug (o(LA)8-RAP)-loaded poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelle for injection and characterize its compatibility and performance versus a RAP-loaded PEG-b-PLA micelle for injection in vitro and in vivo. Monodisperse o(LA)8 was coupled on RAP at the C-40 via DCC/DMAP chemistry, and conversion of o(LA)8-RAP prodrug into RAP was characterized in vitro. Physicochemical properties of o(LA)8-RAP- and RAP-loaded PEG-b-PLA micelles and their antitumor efficacies in a syngeneic 4 T1 breast tumor model were compared. Synthesis of o(LA)8-RAP prodrug was confirmed by 1H NMR and mass spectroscopy. The o(LA)8-RAP prodrug underwent conversion in PBS and rat plasma by backbiting and esterase-mediated cleavage, respectively. O(LA)8-RAP-loaded PEG-b-PLA micelles increased water solubility of RAP equivalent to 3.3 mg/ml with no signs of precipitation. Further, o(LA)8-RAP was released more slowly than RAP from PEG-b-PLA micelles. With added physical stability, o(LA)8-RAP-loaded PEG-b-PLA micelles significantly inhibited tumor growth relative to RAP-loaded PEG-b-PLA micelles in 4 T1 breast tumor-bearing mice without signs of acute toxicity. An o(LA)8-RAP-loaded PEG-b-PLA micelle for injection is more stable than a RAP-loaded PEG-b-PLA micelle for injection, and o(LA)8-RAP converts into RAP rapidly in rat plasma (t1/2 = 1 h), resulting in antitumor efficacy in a syngeneic 4 T1 breast tumor model. |
| تدمد: | 1573-904X 0724-8741 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::4ddeac5a7503eb7df707acaf27947bb5 https://doi.org/10.1007/s11095-019-2600-0 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........4ddeac5a7503eb7df707acaf27947bb5 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1573904X 07248741 |
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