Cancer cell membrane-modified Soluplus® micelles for gemcitabine delivery to pancreatic cancer using a prodrug approach.
Int J Pharm
; 662: 124529, 2024 Sep 05.
Article
en En
| MEDLINE
| ID: mdl-39084580
ABSTRACT
Pancreatic cancer (PC) is one of the most lethal malignancies worldwide and its incidence is increasing. Chemotherapy is often associated to limited efficacy, poor targeting and systemic toxicity. In this work, the hydrophilic gemcitabine (GEM), widely used in PC treatment alone or in combination, was conjugated with vitamin E succinate (VES) and encapsulated in Soluplus® micelles. This prodrug approach facilitated encapsulation of the anticancer drug into the self-assembled copolymer micelles. Soluplus®/VES-GEM micelles were optimized regarding the ratio of the components and the preparation process. The micelles were small-sized (<80 nm), monodisperse, and highly stable, efficiently retaining the conjugate drug and showing significant antiproliferative activity against BxPC3 cell line. To improve biofunctionalization and targeting properties of prepared Soluplus®/VES-GEM micelles, biomimetic modification with PC cell membrane was further attempted by co-extruding PC cell membrane (BxPC3) nanovesicles with Soluplus®/VES-GEM micelles. Several protocols were attempted to prepare the BxPC3-modified Soluplus®/VES-GEM micelles and the outcomes were analyzed in detail. Overall, the results pave the way to innovative PC-targeted nanotherapies by maximizing GEM encapsulation in hydrophobic compartments with high stability and affinity. The results also highlight the need of higher resolution techniques to characterize cell membrane coating of nanocarriers bearing highly hydrophilic shells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
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Polietilenglicoles
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Polivinilos
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Profármacos
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Membrana Celular
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Desoxicitidina
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Gemcitabina
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Micelas
Límite:
Humans
Idioma:
En
Revista:
Int J Pharm
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos