Polyanionic carbohydrate doxorubicin–dextran nanocomplex as a delivery system for anticancer drugs: in vitro analysis and evaluations

Abstract

This study deals with the preparation and investigation of a nanoscale delivery system for the anticancer drug doxorubicin (DOX) using its complexation with polyanionic carbohydrate dextran sulfate (DS). Dynamic light scattering, SEM, and zeta potential determination were used to characterize nanocomplexes. DOX-DS complexation was studied in the presence of ethanol as a hydrogen-bond disrupting agent, NaCl as an electrostatic shielding agent, and chitosan as a positively charged polymer. Thermodynamics of DOX-DS interaction was studied using isothermal titration calorimetry (ITC). A dialysis method was applied to investigate the release profile of DOX from DOX-DS nanocomplexes. Spherical and smooth-surfaced DOX-DS nanocomplexes (250–500 nm) with negative zeta potential were formed at a DS/DOX (w/w) ratio of 0.4–0.6, with over 90% drug encapsulation efficiency. DOX when complexed with DS showed lower fluorescence emission and 480 nm absorbance plus a 15 nm bathometric shift in its visible absorbance spectrum. Electrostatic hydrogen bonding and π-π stacking interactions are the main contributing interactions in DOX-DS complexation. Thermal analysis of DOX-DS complexation by ITC revealed that each DOX molecule binds with 3 DS glycosyl monomers. Drug release profile of nanocomplexes showed a fast DOX release followed by a slow sustained release, leading to release of 32% of entrapped DOX within 15 days. DOX-DS nanocomplexes may serve as a drug delivery system with efficient drug encapsulation and also may be taken into consideration in designing DOX controlled-release systems.

Polyanionic Biopolymers for the Delivery of Pt(II) Cationic Antiproliferative Complexes

“…These features seem to point out that additional forces are involved in the formation of the conjugate. In agreement with what was reported for DOX - DS conjugates [ 30 ], beyond electrostatic interactions, π - π stacking between drug and DS , together with some additional hydrogen bonding, may also occur (see below for further comments). In particular, π - π stacking can be significantly more marked in the case of 3 with respect to the other complexes, justifying its higher loading.…”

“…A similar scenario, associated with the presence of multiple interaction forces, was indeed observed for DOX-DS [ 30 ].…”

Amylase-Sensitive Polymeric Nanoparticles Based on Dextran Sulfate and Doxorubicin with Anticoagulant Activity

“…A necessary condition for a suitable drug composition for in vivo use, is the sufficient content of medicine in a single unit dosage form. In a study by Yousefpour et al [22], a method for the synthesis of particles of DS–Dox NP, in the aqueous phase, was described. The method was simple; however, the drug concentrations in the resulting product were more than one order of magnitude less than those needed to create clinically applicable therapeutic systems (about 2 mg/mL in solutions for intravenous administration [40]).…”

“…One such substance is doxorubicin (Dox). In the work of Yousefpour and co-authors, it was shown that a simple mixing of DS and Dox led to the formation of a specific nanocomplex [22]. Xiaoyun and co-authors have obtained hydrogel from DS and Dox by adding Ca ions, and have studied the impact of these ions on the properties of the resulting product [23].…”

Engineering Biomaterial–Drug Conjugates for Local and Sustained Chemotherapeutic Delivery

“…Dextran sulfate nanoparticles containing DOX can be formed by mixing the drug and polymer. 39 Nearly 100% encapsulation efficiency is achieved at a drug/dextran weight ratio of 0.5. In vitro release from these nanoparticles showed an initial rapid release of 14% over the first 24 hours and a total release of 32% through 15 days.…”