Construction of a dual-responsive dual-drug delivery platform based on the hybrids of mesoporous silica, sodium hyaluronate, chitosan and oxidized sodium carboxymethyl cellulose

Abstract

An intelligent drug delivery platform based on the hybrids of mesoporous silica nanoparticles (MSN), sodium hyaluronate (HA), chitosan (CS) and oxidized sodium carboxymethyl cellulose (oxCMC) is developed, which can be used for dual-responsive dual-drug delivery. Hydrophilic cytarabine (Cyt) is first loaded into the mesopores of the aminated MSN (NH2-MSN), which is encapsulated by the hydrogel of HA and cystamine (Cys) crosslinked via amidation. The Cyt encapsulated hydrogel which is denoted as Cyt/NH2-MSN/HA is co-encapsulated with hydrophobic methotrexate (MTX) into the hydrogel of CS and oxCMC resulted from Schiff base reaction. Since the acylhydrazone bonds (–HC=N–) between CS and oxCMC are sensitive to pH and the disulfide bonds (–S–S–) in Cys are sensitive to glutathione (GSH), the resultant dual-drug encapsulated hydrogel, denoted as Cyt/NH2-MSN/HA/MTX/CS/oxCMC, can be used for dual-responsive (pH and GSH) drug delivery. The results of cell viability demonstrate that the developed dual-drug encapsulated hydrogel has significantly higher efficacy of chemotherapy than that of single-drug (MTX or Cyt) encapsulated hydrogel.