Rational Understanding of Loading and Release of Doxorubicin by UV-Light- and pH-Responsive Poly(NIPAM-co-SPMA) Micelle-like Aggregates

A deep understanding of the interactions between micelle-like aggregates and antineoplastic drugs is paramount to control their adequate delivery. Herein, Poly­(NIPAM-co-SPMA) copolymer nanocarriers were synthesized according to our previous published methodology, and the loading and release of poor...

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Published in:Molecular pharmaceutics 2023-03, Vol.20 (3), p.1490-1499
Main Authors: Espinola-Portilla, Fernando, d’Orlyé, Fanny, Trapiella-Alfonso, Laura, Gutiérrez-Granados, Silvia, Ramírez-García, Gonzalo, Varenne, Anne
Format: Article
Language:English
Subjects:
Analytical chemistry
Antineoplastic Agents
Chemical Sciences
Doxorubicin - chemistry
Drug Carriers - chemistry
Drug Delivery Systems - methods
Hydrogen-Ion Concentration
Micelles
Polymers
Polymers - chemistry
Ultraviolet Rays
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Summary:A deep understanding of the interactions between micelle-like aggregates and antineoplastic drugs is paramount to control their adequate delivery. Herein, Poly­(NIPAM-co-SPMA) copolymer nanocarriers were synthesized according to our previous published methodology, and the loading and release of poorly and highly water-soluble doxorubicin forms (Dox and Dox-HCl, respectively) were evaluated upon UV light irradiation and pH-variation stimuli. Capillary electrophoresis (CE) coupled to a fluorescence detector (LIF) allowed us to specifically characterize these systems and deeply study the loading and release processes. For this purpose, varying concentrations of doxorubicin were tested, and the loading/release rates were indirectly quantified thanks to the “free” doxorubicin concentration in solution. This study highlighted that Dox loading (9.4 μg/mg) was more effective than Dox-HCl loading (5.5 μg/mg). In contrast, 68 and 74% of Dox-HCl were respectively released after 2 min upon pH variation (from 7.4 to 6.0) and combined UV + pH 6.0 stimuli, while only 27% of Dox was invariably released upon application of the same stimuli. These results are coherent with the characteristics of both DoxHCl and Dox: Electrostatic interactions between Dox-HCl and the micelle-membrane structure (NIPAM) seemed predominant, while hydrophobic interactions were expected between Dox and the SP moieties at the inner part of the micelle-like aggregate, leading to different behaviors in both loading and release of the two doxorubicin forms. For doxorubicin loading concentrations higher than 3 μM, the electrophoretic profiles presented an additional peak. Thanks to CE characterizations, this peak was attributed to the formation of a complex formed between the nonaggregated copolymer and the doxorubicin molecules. This report therefore undergoes deep characterization of the dynamic formation of different micelle/drug complexes involved in the global drug-delivery behavior and therefore contributes to the development of more effective stimuli-responsive nanocarriers.
ISSN:1543-8384
1543-8392
DOI:10.1021/acs.molpharmaceut.2c00690