Biodegradable micellar HPMA-based polymer-drug conjugates with betulinic acid for passive tumor targeting

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00465442" target="_blank" >RIV/61389013:_____/16:00465442 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1021/acs.biomac.6b00947" target="_blank" >http://dx.doi.org/10.1021/acs.biomac.6b00947</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.biomac.6b00947" target="_blank" >10.1021/acs.biomac.6b00947</a>

Result language
angličtina
Original language name
Biodegradable micellar HPMA-based polymer-drug conjugates with betulinic acid for passive tumor targeting
Original language description
Here, we present the synthesis, physicochemical, and preliminary biological characterization of micellar polymer-betulinic acid (BA) conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carriers, enabling the controlled release of cytotoxic BA derivatives in solid tumors or tumor cells. Various HPMA copolymer conjugates differing in the structure of the spacer between the drug and the carrier were synthesized, all designed for pH-triggered drug release in tumor tissue or tumor cells. The high molecular weight of the micellar conjugates should improve the uptake of the drug in solid tumors due to the Enhanced permeability and retention (EPR) effect. Nevertheless, only the conjugate containing BA with methylated carboxyl groups enabled pH-dependent controlled release in vitro. Moreover, drug release led to the disassembly of the micellar structure, which facilitated elimination of the water-soluble HPMA copolymer carrier from the body by renal filtration. The methylated BA derivative and its polymer conjugate exhibited high cytostatic activity against DLD-1, HT-29, and HeLa carcinoma cell lines and enhanced tumor accumulation in HT-29 xenograft in mice.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CD - Macromolecular chemistry
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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