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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Administration, Inhalation
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Berberine / administration & dosage*
  • Berberine / pharmacokinetics
  • Berberine / therapeutic use
  • Boronic Acids / chemistry
  • Boronic Acids / metabolism*
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Drug Delivery Systems
  • Drug Liberation
  • Etoposide / administration & dosage*
  • Etoposide / pharmacokinetics
  • Etoposide / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Mice
  • N-Acetylneuraminic Acid / metabolism
  • Nanocomposites / chemistry
  • Serum Albumin, Human / chemistry
  • Serum Albumin, Human / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Boronic Acids
  • Drug Carriers
  • Berberine
  • Etoposide
  • N-Acetylneuraminic Acid
  • Serum Albumin, Human