Layer-by-layer development of chitosan/alginate-based platelet-mimicking nanocapsules for augmenting doxorubicin cytotoxicity against breast cancer

Alaa Ibrahim; Islam A Khalil; Mohamed Y Mahmoud; Alaa F Bakr; Monira G Ghoniem; Eida S Al-Farraj; Ibrahim M El-Sherbiny

doi:10.1016/j.ijbiomac.2022.11.107

Layer-by-layer development of chitosan/alginate-based platelet-mimicking nanocapsules for augmenting doxorubicin cytotoxicity against breast cancer

Int J Biol Macromol. 2023 Jan 15:225:503-517. doi: 10.1016/j.ijbiomac.2022.11.107. Epub 2022 Nov 17.

Authors

Alaa Ibrahim¹, Islam A Khalil², Mohamed Y Mahmoud³, Alaa F Bakr⁴, Monira G Ghoniem⁵, Eida S Al-Farraj⁵, Ibrahim M El-Sherbiny⁶

Affiliations

¹ Nanomedicine Research Labs, Center for Materials Sciences, Zewail City of Science and Technology, 6th of October City, 12578 Giza, Egypt.
² Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University of Science and Technology (MUST), 6th of October, Giza 12582, Egypt.
³ Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Egypt.
⁴ Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt.
⁵ Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13623, Saudi Arabia.
⁶ Nanomedicine Research Labs, Center for Materials Sciences, Zewail City of Science and Technology, 6th of October City, 12578 Giza, Egypt. Electronic address: ielsherbiny@zewailcity.edu.eg.

PMID: 36403763
DOI: 10.1016/j.ijbiomac.2022.11.107

Abstract

Breast carcinoma is considered one of the most invasive and life-threatening malignancies in females. Mastectomy, radiation therapy, hormone therapy and chemotherapy are the most common treatment choices for breast cancer. Doxorubicin (DOX) is one of the most regularly utilized medications in breast cancer protocols. However, DOX has showed numerous side effects including lethal cardiotoxicity. This study aims to fortify DOX cytotoxicity and lowering its side effects via its combining with the antidiabetic metformin (MET) as an adjuvant therapy, along with its effective delivery using natural platelet-rich plasma (PRP), and newly-developed PRP-mimicking nanocapsules (NCs). The PRP-mimicking NCs were fabricated via layer-by-layer (LBL) deposition of oppositely charged biodegradable and biocompatible chitosan (CS) and alginate (ALG) on a core of synthesized polystyrene nanoparticles (PS NPs) followed by removal of the PS core. Both natural PRP and PRP-mimicking NCs were loaded with DOX and MET adjuvant therapy, followed by their physicochemical characterizations including DLS, FTIR, DSC, and morphological evaluation using TEM. In-vitro drug release studies, cytotoxicity, apoptosis/necrosis, and cell cycle analysis were conducted using MCF-7 breast cancer cells. Also, an in-vivo assessment was carried out using EAC-bearing balb/c mice animal model to evaluate the effect of DOX/MET-loaded natural PRP and PRP-mimicked NCs on tumor weight, volume and growth biomarkers in addition to analyzing the immunohistopathology of the treated tissues. Results confirmed the development of CS/ALG-based PRP-mimicking NCs with a higher loading capacity of both drugs (DOX and MET) and smaller size (259.7 ± 19.3 nm) than natural PRP (489 ± 20.827 nm). Both in-vitro and in-vivo studies were in agreement and confirmed that MET synergized the anticancer activity of DOX against breast cancer. Besides, the developed LBL NCs successfully mimicked the PRP in improving the loaded drugs biological efficiency more than free drugs.

Keywords: Alginate; Breast cancer; Chitosan; Doxorubicin; Layer-by-layer; Metformin; Nanocapsules; Platelet-rich plasma.

MeSH terms

Alginates / chemistry
Animals
Chitosan* / chemistry
Doxorubicin / chemistry
Female
Mastectomy
Mice
Nanocapsules* / chemistry
Nanoparticles* / chemistry
Neoplasms*

Substances

Nanocapsules
Chitosan
Alginates
Doxorubicin