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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 Publisher Pubmed



Akbari A1 ; Varshosaz J1 ; Minaiyan M2 ; Heydari P3 ; Talebi A4 ; Salahi M1 ; Jahanian Najafabadi A5
Authors
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Authors Affiliations
  1. 1. Novel Drug Delivery Systems Research Center, Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Materials Engineering, Isfahan University of Technology, Isfahan, 84156-83111, Iran
  4. 4. Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: International Journal of Pharmaceutics Published:2024


Abstract

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. © 2024 Elsevier B.V.
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