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

Yousefpour P, Atyabi F, Farahani EV, Sakhtianchi R, Dinarvand R - Int J Nanomedicine (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

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.

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Schematic illustration of doxorubicin–dextran sulfate nanocomplexation.
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f8-ijn-6-1487: Schematic illustration of doxorubicin–dextran sulfate nanocomplexation.

Mentions: As DS/DOX ratios increase up to 0.4, more DOX molecules become involved in electrostatic and hydrogen-bonding interactions with DS chains and stacking interactions with each other, and consequently DOX absorbance decreases. At a DS/DOX ratio of 0.4, DOX comes into equilibrium between bulk solution and DOX-DS complexes; DS ratio is high enough to accommodate a maximum fraction of DOX. As illustrated in Figure 8, in the 0.4–0.6 range, a stacked array of DOX molecules acts as a physical crosslinker which, along with DOX-DS electrostatic interaction, makes DOX-DS complexes compact enough to form drug–polymer nanocomplexes. With further addition of DS to the system at DS/DOX > 0.6, DOX molecules are distributed among a higher number of DS chains and are positioned farther from each other; stacking interactions are weakened and the DOX-DS network is loosened. Therefore, DOX-DS complexes are not compact enough to form nanocomplexes and are of insufficient density to sediment during ultracentrifugation, which explains the descending part of the encapsulation curve. In fact, a close look at the absorption spectrum of the supernatant of ultracentrifuged DOX-DS complexes reveals the bathometric shift in DOX spectrum at DS/DOX > 0.6; this confirms the presence of DOX-DS complexes not sedimenting by ultracentrifugation.


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

Yousefpour P, Atyabi F, Farahani EV, Sakhtianchi R, Dinarvand R - Int J Nanomedicine (2011)

Schematic illustration of doxorubicin–dextran sulfate nanocomplexation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3141874&req=5

f8-ijn-6-1487: Schematic illustration of doxorubicin–dextran sulfate nanocomplexation.
Mentions: As DS/DOX ratios increase up to 0.4, more DOX molecules become involved in electrostatic and hydrogen-bonding interactions with DS chains and stacking interactions with each other, and consequently DOX absorbance decreases. At a DS/DOX ratio of 0.4, DOX comes into equilibrium between bulk solution and DOX-DS complexes; DS ratio is high enough to accommodate a maximum fraction of DOX. As illustrated in Figure 8, in the 0.4–0.6 range, a stacked array of DOX molecules acts as a physical crosslinker which, along with DOX-DS electrostatic interaction, makes DOX-DS complexes compact enough to form drug–polymer nanocomplexes. With further addition of DS to the system at DS/DOX > 0.6, DOX molecules are distributed among a higher number of DS chains and are positioned farther from each other; stacking interactions are weakened and the DOX-DS network is loosened. Therefore, DOX-DS complexes are not compact enough to form nanocomplexes and are of insufficient density to sediment during ultracentrifugation, which explains the descending part of the encapsulation curve. In fact, a close look at the absorption spectrum of the supernatant of ultracentrifuged DOX-DS complexes reveals the bathometric shift in DOX spectrum at DS/DOX > 0.6; this confirms the presence of DOX-DS complexes not sedimenting by ultracentrifugation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

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.

Show MeSH