Hyaluronan-Cyclodextrin Conjugates as Doxorubicin Delivery Systems.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Cyclodextrin-based nanoparticles are explored for anticancer drug delivery.
• Hyaluronic acid (HA) is a biocompatible polymer with potential in drug targeting.
• Developing efficient and green synthesis methods for drug delivery systems is crucial.

Purpose of the Study:

• To synthesize and characterize hyaluronic acid-cyclodextrin conjugates for doxorubicin delivery.
• To compare the efficacy of different molecular weights of HA-based nanoparticles.
• To evaluate the in vitro anticancer activity and drug uptake of the developed system.

Main Methods:

• Green synthesis of hyaluronic acid backbone functionalized with cyclodextrins.
• Preparation of doxorubicin-loaded nanoparticles using HA with 11 kDa and 45 kDa molecular weights.
• In vitro assessment of doxorubicin solubility, cellular uptake, and antiproliferative activity in SK-N-SH and SK-N-SH-PMA cancer cell lines.

Main Results:

• Hyaluronan-cyclodextrin conjugates successfully increased doxorubicin water solubility.
• Enhanced doxorubicin uptake and antiproliferative activity were observed in CD44-overexpressing SK-N-SH-PMA cells compared to SK-N-SH cells.
• The 45 kDa HA-based system showed superior drug carrier effectiveness, reducing doxorubicin's IC50 by 56% at an 8/1 doxorubicin/polymer ratio.
• At a 16/1 doxorubicin/polymer ratio, HA polymers improved doxorubicin's antiproliferative activity by approximately 70% in both cell lines.

Conclusions:

• Hyaluronic acid-cyclodextrin conjugates represent a promising green-synthesized nanocarrier for doxorubicin.
• The system demonstrates improved drug solubility, enhanced cellular uptake, and increased anticancer efficacy, particularly in CD44-positive cancer cells.
• The molecular weight of hyaluronic acid influences the drug delivery performance, with higher molecular weight (45 kDa) showing greater potential.