Hyaluronan-Cyclodextrin Conjugates as Doxorubicin Delivery Systems

Abstract

In the last years, nanoparticles based on cyclodextrins have been widely investigated for the delivery of anticancer drugs. In this work, we synthesized nanoparticles with a hyaluronic acid backbone functionalized with cyclodextrins under green conditions. We functionalized hyaluronic acid with two different molecular weights (about 11 kDa and 45 kDa) to compare their behavior as doxorubicin delivery systems. We found that the new hyaluronan-cyclodextrin conjugates increased the water solubility of doxorubicin. Moreover, we tested the antiproliferative activity of doxorubicin in the presence of the new cyclodextrin polymers in SK-N-SH and SK-N-SH-PMA (over-expressing CD44 receptor) cancer cells. We found that hyaluronan-cyclodextrin conjugates improved the uptake and antiproliferative activity of doxorubicin in the SK-N-SH-PMA compared to the SK-N-SH cell line at the ratio 8/1 doxorubicin/polymer. Notably, the system based on hyaluronan (45 kDa) was more effective as a drug carrier and significantly reduced the IC50 value of doxorubicin by about 56%. We also found that hyaluronic acid polymers determined an improved antiproliferative activity of doxorubicin (IC50 values are on average reduced by about 70% of free DOXO) in both cell lines at the ratio 16/1 doxorubicin/polymer.

Cucurbituril-Based Porphyrin Cascade Assembly for Cell Imaging and Targeted Drug Delivery

“…Due to the cancer cell-targeting properties and the overall negatively charged nature of these obtained supramolecular nanoparticles, DOX, an anticancer drug that is widely used in tumor therapy, was chosen as a model drug to explore the photodynamic and chemotherapeutic performance of ternary assembly at the cellular level. The apparent binding affinity of DOX with HACD is known up to 10 4 M –1 . , Therefore, through the UV–vis absorption standard curve of DOX at different concentrations, the encapsulation and loading efficiencies were calculated as 55.1 and 18.0%, respectively (Figure S13, Supporting Information). In addition, the presence of DOX did not change the morphology of the nanoparticulate assembly (Figure S10e, Supporting Information).…”

“…The apparent binding affinity of DOX with HACD is known up to 10 4 M −1 . 35,36 Therefore, through the UV−vis absorption standard curve of DOX at different concentrations, the encapsulation and loading efficiencies were calculated as 55.1 and 18.0%, respectively (Figure S13, Supporting Information). In addition, the presence of DOX did not change the morphology of the nanoparticulate assembly (Figure S10e, Supporting Information).…”

Formulation and Evaluation of PLGA Nanoparticulate-Based Microneedle System for Potential Treatment of Neurological Diseases

“…Figure 3A shows that when the probe is displaced to the tip length of Rh-NPs-DMNs at 650 μm, the fracture force of the tip is 2.75 ± 0.03 N (n = 12, approximately four needles), which is 1.8 times higher than that of Rh-DMNs, generating a force sufficient to overcome the elastic barrier of the skin. The reason for this may be related to the fact that the 2-HP-β-CD-based PLGA system forms hydrogen bonding with HA, 30 restraining the migration of molecular chains and tightening the structure, thus increasing the mechanical strength of this composite. The maximum mechanical strength value of Rh-NPs-DMNs can reach 299.78 ± 1.74 N (n = 12; Figure 3B) when the maximum compression distance is approximately 2 mm, whereas that of Rh-DMNs is only 196.62 ± 1.71 N (n = 12).…”