Effects of Membrane PEGylation on Entry and Location of Antifungal Drug Itraconazole and Their Pharmacological Implications
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10362240" target="_blank" >RIV/00216208:11110/17:10362240 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1021/acs.molpharmaceut6b00969" target="_blank" >http://dx.doi.org/10.1021/acs.molpharmaceut6b00969</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.molpharmaceut6b00969" target="_blank" >10.1021/acs.molpharmaceut6b00969</a>
Alternative languages
Result language
angličtina
Original language name
Effects of Membrane PEGylation on Entry and Location of Antifungal Drug Itraconazole and Their Pharmacological Implications
Original language description
Itraconazole (ITZ) is arr antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery Mechanism for ITZ to :alleviate this problem. Furthermore, PEGylation, the inclusion in the formulation of a protective "stealth sheath" of poly(ethylene glycol) around carrier particles, is widely used to increase circulation time in the bloodstream and hence efficacy. Together; these themes highlight the importance of mechanistic and structural understanding of incorporation info liposomes both with and without PEGylation because it can provide a potential foundation for the rational design of LDS-based systems for delivery of ITZ, using alternate protective polymers or formulations. Here we have combined atomistic simulations, cryo-TEM, Langmuir film balance, and fluorescence quenching experiments to explore how ITZ interacts with both pristine and PEGylated liposomes. We found that the drug can be incorporated into conventional and PEGylated liposomes for drug, concentrations up to 15 mol % without phase separation. We observed that, in addition to its protective properties, PEGylation significantly increases the stability of liposomes that host ITZ. In a 1-palmitoyl2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer without PEGylation, ITZ was found to reside inside the lipid bilayer between the glycerol and the double-bond regions-of POPC, adopting a largely parallel orientation along the membrane surface: In a PEGylated liposome; ITZ partitions mainly to the PEG layer. The results provide a solid basis for further development of liposome-based delivery systems.
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
10600 - Biological sciences
Result continuities
Project
<a href="/en/project/GBP302%2F12%2FG157" target="_blank" >GBP302/12/G157: Dynamics and Organization of Chromosomes in the Cell Cycle and during Differentiation under Normal and Pathological Conditions</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Pharmaceutics
ISSN
1543-8384
e-ISSN
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Volume of the periodical
14
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
1057-1070
UT code for WoS article
000398426100009
EID of the result in the Scopus database
2-s2.0-85019028641