Fabrication of an Injectable Star-polylactide/Thiolated Hyaluronate Hydrogel as a Double Drug-Delivery System for Cancer Treatment

Abstract

Unsatisfactory solid-tumor penetration or rapid metabolism of nanomaterials limits their therapeutic efficacy. Here, we designed an injectable thiolated hyaluronate (HA-SH) hydrogel as a stable drugreleasing platform for in situ tumor treatment. Biodegradable star-shaped polylactide (S-PLLA) was first synthesized and fabricated to porous microspheres to encapsulate hydrophobic curcumin (Cur@S-PLLA), which was then blended with hydrophilic doxorubicin (Dox) and the HA-SH precursor to form composite in situ formable hydrogels [Cur@S-PLLA/ (Dox)HA-SH]. The results showed that adding the microspheres improved the performance of the hydrogel, such as decreasing the gelation time from 1080 s to 960 s and also the swelling ratio. The mechanical strength increased from 27 to 45 kPa. In addition, the double drug system guaranteed a sustained release of drugs, releasing Dox at the early stage, with the continuous later release of Cur after gel swelling or S-PLLA degradation to achieve long-lasting tumor suppression, which inhibits the survival of cancer cells. The inhibitory effects of the hydrogels on MCF-7 were studied. The cell activity in the doubleloaded hydrogel was significantly lower than that of the control groups, and apparent dead cells appeared in 2 days and fewer living cells with time. Flow cytometry revealed that the Cur@S-PLLA/(Dox)HA-SH group had the highest apoptosis ratio of 86.60% at 12 h, and the drugs caused the cell cycle to be blocked in phase M to reduce cell division. In summary, the innovative release platform is expected to be used in long-lasting tumor suppression and provides more ideas for the design of drug carriers.

Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions

“…Other synthetic polymer hydrogels : Hydrogels composed of synthetic polymers such as polyethylene oxide, 260 polylactic acid, 261 and polypropylene fumarate 262 offer tunable mechanical strengths, but these materials typically suffer from poor biocompatibility and inadequate cell adhesion properties. Additionally, their rapid degradation and potential toxic byproducts can be significant drawbacks, further limiting their in vivo applications.…”

Electrospray doxorubicin‐loaded polycaprolactone‐polyethylene glycol nanospheres/poloxamer‐chitosan thermogel: A promising candidate for clinical applications

“…Toxicity laboratory studies proved that the composite systems could retain the drug for a longer period and showed more favorable anticancer properties compared to the nanoparticle system. Therefore, it can be suggested that the composite injectable gel containing nanoparticles can be a candidate for the local drug release that can fill the vacuum formed when removal of the solid tumor is carried out surgically 44 . Over prefabricated scaffolds, injectable in‐situ formed ones have many benefits.…”