Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel

Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration

“…As shown in Figure 1(B), the characteristic peaks of HA appeared at 2.0 ppm and 3.3-4.7 ppm. Successful introduction of deoxycholic acid (DOCA) and glycyrrhetinic acid (GA) into HA polymers was confirmed by the characteristic peaks, which appeared in the range of 0.6-1.6 ppm for DOCA and 1.0-1.4 ppm for GA (Li et al, 2012;Zhang et al, 2013a). In addition, the peaks at 8.04 and 8.02 ppm further confirmed the formation of new amide linkages in HA-adh-DOCA and HA-adh-GA conjugate, respectively.…”

“…Synthesis of amphiphilic HA-adh-DOCA conjugates and HA-adh-GA conjugates Firstly, carboxylic acid groups of HA were modified with adipic dihydrazide (adh) by use of the EDC reaction, resulting in the formation of HA-adh conjugates, as described by our and other groups (Luo & Prestwich, 1999;Li et al, 2012). Secondly, amphiphilic HA-adh-DOCA conjugates and HAadh-GA conjugates were synthesized by coupling HA-adh conjugate with deoxycholic acid (DOCA) and glycyrrhetinic acid (GA), respectively, via the formation of amide linkage (Li et al, 2012;Zhang et al, 2013a).…”

“…Secondly, amphiphilic HA-adh-DOCA conjugates and HAadh-GA conjugates were synthesized by coupling HA-adh conjugate with deoxycholic acid (DOCA) and glycyrrhetinic acid (GA), respectively, via the formation of amide linkage (Li et al, 2012;Zhang et al, 2013a). In brief, carboxylic acid group of DOCA and GA was reactivated by equimolar amounts of EDC and NHS in DMF at 0 C for 4 h and then at 20 C overnight to form NHS ester of DOCA and GA, respectively.…”

“…Our previous study has reported a novel amphiphilic hyaluronic acid-deoxycholic acid (HA-adh-DOCA) conjugate, taking deoxycholic acid as hydrophobic moieties (Li et al, 2012). The micelle formed by HA-adh-DOCA conjugate has great capability in solubilization of water-insoluble drug, such as paclitaxel with the high drug-loading capacities of 33.0 ± 0.5%.…”

Bioreducible Micelles Self-Assembled from Poly(ethylene glycol)-Cholesteryl Conjugate As a Drug Delivery Platform

“…In biological systems, GSH, a cysteine-containing tripeptide capable of reducing disulfide linkages, is found in extracellular (~2 µM) and intracellular (1-10 mM) compartments at concentrations, known to be several times higher in tumors than they are in healthy tissues [20]. Therefore, amphiphilic copolymers containing disulfide linkages within the hydrophobic backbone or a single disulfide bond at the connection of the two polymer blocks have been prepared for use in redox-responsive drug delivery [21][22][23][24]. However, the preparation of disulfide-bearing polymers is often complex because it requires thiol-disulfide exchange reactions to introduce disulfide bonds at the junctions or the side chains of diblock copolymers.…”