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J Control Release. 2018 Sep 10;285:230-243. doi: 10.1016/j.jconrel.2018.07.014. Epub 2018 Jul 25.

Targeting sialic acid residues on lung cancer cells by inhalable boronic acid-decorated albumin nanocomposites for combined chemo/herbal therapy.

Author information

1
Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
2
Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
3
Medical Research Institute (MRI), Alexandria University, Alexandria 21527, Egypt.
4
Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
5
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Taoyuan 333, Taiwan; Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan. Electronic address: fajy@mail.cgu.edu.tw.
6
Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. Electronic address: aelzoghby@bwh.harvard.edu.

Abstract

Etoposide (ETP), as a potential treatment for lung cancer, has limited application due to its poor solubility, and systemic side effects. In the current study, we propose inhalable boronate-targeted HSA nanocomposites for combined delivery of ETP and the herbal drug, berberine (BER) for localized therapy of lung cancer. First, ETP was pre-formulated as phospholipid complex (EPC) to enhance drug solubility and facilitate its encapsulation within the hydrophilic albumin nanoparticles (NPs). Second, EPC and BER were then co-loaded with high efficiency into HSA NPs as a synergistic therapy for lung cancer. The NPs displayed suitable size around 200 nm and sequential drug release pattern. Moreover, conjugation of aminophenylboronic acid (APBA) to HSA NPs resulted in enhanced cytotoxicity and internalization into A549 lung cancer cells, compared to non-targeted NPs or free drugs via binding to sialic acid residues over-expressed by cancer cells. Using mannitol as a spray-drying carrier, the developed inhalable nanocomposites demonstrated deep pulmonary deposition, confirmed by small MMAD (2.112 μm) and high FPF (77.86%). In vivo investigations in lung cancer animal models revealed the superior anti-tumor efficacy of the inhalable nanocomposites. Overall, the inhalable APBA-HSA nanocomposites offered an alternative strategy for systemic delivery of ETP and BER in lung cancer therapy.

KEYWORDS:

Albumin nanoparticles; Drug-phospholipid complex; Inhalable nanocomposites; Lung cancer; Phenylboronic targeting; Pulmonary drug delivery

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