Platelet-cloaked alginate-poly (β-amino ester) a novel platform bioinspired polyelectrolyte nanoparticle for targeted delivery of carboplatin in breast cancer: An in vitro/in vivo study

[Display omitted] •Crb-PβAE-ALG NPs were prepared by ionic gelation.•The NPs were subsequently coated by platelet membrane (PltM) using ultra-sonication method.•Bioinspired Crb-loaded platelets (Plt@Crb) were also prepared for comparison.•Plt@Crb and PltM@Crb-PβAE-ALG NPs exhibited enhanced cytotoxi...

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Veröffentlicht in:International journal of pharmaceutics 2024-11, Vol.665, p.124720, Article 124720
Hauptverfasser: Akbari, Aliakbar, Varshosaz, Jaleh, Minaiyan, Mohsen, Heydari, Parisa, Talebi, Ardeshir, Salahi, Mehrnaz, Jahanian Najafabadi, Ali
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Sprache:eng
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Zusammenfassung:[Display omitted] •Crb-PβAE-ALG NPs were prepared by ionic gelation.•The NPs were subsequently coated by platelet membrane (PltM) using ultra-sonication method.•Bioinspired Crb-loaded platelets (Plt@Crb) were also prepared for comparison.•Plt@Crb and PltM@Crb-PβAE-ALG NPs exhibited enhanced cytotoxicity in 4 T1 cells.•PltM@Crb-PβAE-ALG NPs demonstrated superior therapeutic efficacy than Plt@Crb in vivo. Triple-negative breast cancer (TNBC) has poor prognosis. Carboplatin (Crb) is a widely used chemotherapeutic agent, in TNBC but with serious systemic toxicity and poor tumor targeting. Bioinspired drug-loaded platelets (Plt) and Plt-coated nanocarriers evade macrophage phagocytosis by membrane proteins like CD47. The goal of this study was preparation of a novel alginate-poly (β-amino ester) (PβAE) nanoparticles (NPs) for targeted delivery of Crb to TNBC cells by developing and comparison of two bioinspired carriers of Plt membrane (PltM) coated Crb-loaded alginate-poly (β-amino ester) nanoparticles (PltM@Crb-PβAE-ALG NPs) and Plt loaded Crb (Plt@Crb). The NPs were prepared by ionic gelation and subsequently were coated by platelet membrane using ultra-sonication method. The loading efficiency, release profile, and in vitro cytotoxicity of both formulations were evaluated on HUVEC and 4 T1 cells. Additionally, the in vivo tumor targeting, therapeutic efficacy, and organ toxicity of the two formulations were assessed in a murine tumor model. Results showed both Plt@Crb and (PltM@Crb-PβAE-ALG NPs) exhibited high drug loading efficiency, sustained release, enhanced cytotoxicity against 4 T1 cells, and decreased cytotoxicity in normal cells (HUVEC) in vitro. In vivo studies revealed that although both formulations considerably improved tumor inhibition compared to free Crb, but the PltM@Crb-PβAE-ALG NPs demonstrated superior cytotoxicity and therapeutic efficacy, thanks to improved Crb’s internalization efficiency, enhanced stability, and controlled release properties.
ISSN:0378-5173
1873-3476
1873-3476
DOI:10.1016/j.ijpharm.2024.124720