Multilayer Microcapsules as Anti‐Cancer Drug Delivery Vehicle: Deposition, Sustained Release, and in vitro Bioactivity

Abstract

Summary: A drug delivery system based on spontaneous deposition of soluble, low-molecular-weight therapeutic agents has been developed for the purpose of sustaining drug release. Layer-by-layer assembly of oppositely charged polyelectrolytes onto melamine formaldehyde (MF) colloidal particles, followed by removal of the cores at low pH has yielded intact hollow microcapsules having the ability to induce deposition of various water-soluble substances. Dynamic observation by confocal laser scanning microscopy provided direct evidence of such deposition. Dependence of loading rate on molecular weight was investigated. Efficient loading of an anti-cancer drug, daunorubicin (DNR), was confirmed by transmission electron microscopy (TEM). Its release was quantified by fluorometry. The results indicated that loading, and subsequent release, could be tuned by factors such as feeding concentrations, temperature, and salt concentrations. The intrinsic mechanism of loading and release was discussed taking into account the interaction between the drugs and the poly(styrene sulfonate)/MF complex existing in the hollow capsules. With culture of the HL-60 cell line, a kind of human leukemia cell, the presence of DNR-loaded capsules was seen to steadily decrease the cytoviability. Fluorescence intensity averaged from inside the circles as a function of incubation time.