Biointerfacial giant capsules with high paclitaxel loading and magnetic targeting for breast tumor therapy

Abstract

High drug loading, targeted delivery, prolonged drug release, and low systemic toxicity are effective weapons for hydrophobic drug delivery systems to solve serious concerns in poor water-solubility and toxicity of paclitaxel (PTX). Herein, we reported that biointerfacial giant multilayer microcapsules (BGMs) with the feature of high-density drug loading and high-efficiency magnetic delivery were fabricated templated by PTX-liposome-microbubble complex using the layer-by-layer self-assembly (LbL) technique. The drug loading capacity of BGMs was improved by optimizing the structure of microbubbles and capsules to increase the PTX-contained layers, and the resultant BGMs exhibited high drug loading content (50.56 ± 0.09 %) and sustained drug release properties. The BGMs with an average diameter of 74.1 ± 12.1 µm and an average thickness of 275.5 ± 48.4 nm contained abundant magnetic nanoparticles (MNPs) in their cavity, which endowed these capsules with outstanding magnetic properties and fast magnetophoretic velocity in the blood (∼0.3 mm/s, ▽B = 1 T/mm). Moreover, both in vitro and in vivo studies demonstrated that the biocompatible PTX-loaded magnetic BGMs (Capsule@PLMPPL) caused notable death (71.3 ± 2.9 %) of 4 T1 breast cancer cells through PTX diffusion, capsules degradation, and subsequent endocytosis by cancer cells, and ultimately effectively inhibited tumor growth. In general, the developed BGM with good deformability and degradation was the first reported giant polyelectrolyte capsule to be used in tumor therapy, which could notably improve the therapeutic efficacy of PTX while reducing its side effects.

Keywords: Biointerfacial giant microcapsules; Breast tumor therapy; Hydrophobic drug delivery systems; Layer-by-layer self-assembly technique; Paclitaxel.