Biocompatible disulphide cross-linked sodium alginate derivative nanoparticles for oral colon-targeted drug delivery

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):353-369. doi: 10.1080/21691401.2018.1557672.

Abstract

The application of layer-by-layer (LbL) approach on nanoparticle surface coating improves the colon-specific drug delivery of insoluble drugs. Here, we aimed to formulate a self-assembled cysteamine-based disulphide cross-linked sodium alginate with LbL self-assembly to improve the delivery of paclitaxel (PCX) to colonic cancer cells. Cysteamine was conjugated to the backbone of oxidized SA to form a core of self-assembled disulphide cross-linked nanospheres. P3DL was selected for PCX loading and fabricated LbL with poly(allylamine hydrochloride) (PAH) and poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSCMA) resulting from characterization and drug release studies. P3DL-fabricated PCX-loaded nanospheres (P3DL/PAH/PSSCMA) exhibited an encapsulation efficiency of 77.1% with cumulative drug release of 45.1%. Dynamic light scattering analysis was reported at 173.6 ± 2.5 nm with polydispersity index of 0.394 ± 0.105 (zeta potential= -58.5 mV). P3DL/PAH/PSSCMA demonstrated a pH-dependent swelling transition; from pH 1 to 7 (102.2% increase). The size increased by 33.0% in reduction response study after incubating with 10 mM glutathione (day 7). HT-29 cells showed high viabilities (86.7%) after treatment with the fabricated nanospheres at 0.8 µg/mL. Cellular internalization was successful with more than 70.0% nanospheres detected in HT-29 cells. Therefore, this fabricated nanospheres may be considered as potential nanocarriers for colon cancer-targeted chemotherapeutic drug delivery.

Keywords: Sodium alginate; colon drug delivery; disulphide cross-linked nanospheres; layer-by-layer nanospheres; reduction response.

MeSH terms

  • Administration, Oral
  • Alginates / chemistry*
  • Biocompatible Materials / chemistry*
  • Biological Transport
  • Colon / metabolism*
  • Cysteamine / chemistry
  • Disulfides / chemistry*
  • Drug Carriers / chemistry
  • Drug Liberation
  • Drug Stability
  • HT29 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Nanoparticles / chemistry*
  • Nanospheres / chemistry
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry*
  • Paclitaxel / metabolism
  • Particle Size
  • Surface Properties

Substances

  • Alginates
  • Biocompatible Materials
  • Disulfides
  • Drug Carriers
  • Cysteamine
  • Paclitaxel