HPMA copolymer conjugate with pirarubicin: In vitro and ex vivo stability and drug release study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F18%3A00482175" target="_blank" >RIV/61389013:_____/18:00482175 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.ijpharm.2017.11.011" target="_blank" >http://dx.doi.org/10.1016/j.ijpharm.2017.11.011</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ijpharm.2017.11.011" target="_blank" >10.1016/j.ijpharm.2017.11.011</a>
Alternative languages
Result language
angličtina
Original language name
HPMA copolymer conjugate with pirarubicin: In vitro and ex vivo stability and drug release study
Original language description
We have developed a tumor environment-responsive polymeric anticancer prodrug containing pirarubicin (THP) conjugated to N-(2-hydroxypropyl) methacrylamide copolymer (PHPMA), [P-THP], through a spacer containing pH-sensitive hydrazone bond, that showed remarkable therapeutic effect against various tumor models and in a human pilot study. Toward clinical development, here we report THP release profile from its HPMA copolymer conjugate, the conjugate stability, protein and cell-binding and solubility of P-THP. Size exclusion chromatography of P-THP (molecular weight 38 kDa) showed similar hydrodynamic volume as bovine serum albumin (BSA) in aqueous solution, with no apparent interactions with BSA, nor aggregation by itself. pH-responsive release of free THP was reconfirmed at pHs 6.5 and lower. The drug release was significantly affected by a type of used buffer. Phosphate buffer seems to facilitate faster hydrazone bond cleavage at pH 7.4 whereas higher stability was achieved in L-arginine solution which yielded only little cleavage and THP release, approx. 15% within 2 weeks at the same pH at 25 °C. Furthermore, ex vivo study using sera of different animal species showed very high stability of P-THP. Incubation with blood showed high stability of P-THP during circulation, without binding to blood cells. These findings revealed that L-arginine solution provides appropriate media for formulation of P-THP infusion solution as tumor-targeted polymeric anticancer drug based on EPR effect.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Pharmaceutics
ISSN
0378-5173
e-ISSN
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Volume of the periodical
536
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
8
Pages from-to
108-115
UT code for WoS article
000424259100011
EID of the result in the Scopus database
2-s2.0-85035026360