Common chemotherapy is often associated with adverse effects and unsatisfied patient compliance. As an alternative approach localized chemotherapy ,with the ability to reduce systemic toxicity, is preferred.
Injectable thermogel to deliver chemotherapeutics in a minimally invasive manner and to achieve long term sustained release at tumor sites to minimize side effects is attractive for improved chemotherapy and precision medicine, but its rational design remains a challenge.
Recently, Dr. Wu at Xiamen University China and Dr. Loh at the Institute of Materials Research and Engineering Singapore have designed a biocompatible and injectable hydrogel based on thermogelling copolymer. This copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate] (PHB), hydrophilic poly(ethylene glycol) (PEG), and temperature sensitive poly(propylene glycol) (PPG) blocks linked by urethane linkages is designed to show thermogelling characteristics which are beneficial for minimally invasive injection and safe degradation. Furthermore, a rodent model of hepatocarcinoma was performed to evaluate the in vivo applications of this PHB-based thermogel. By taking advantage of temperature sensitive sol-to-gel transition, paclitaxel (PTX) and doxorubicin (DOX) as model chemotherapeutic drugs can be suspended in solution at 4 °C and can easily and precisely be injected into the tumor site to form a gel depot at 37 °C. More importantly, this hydrogel can achieve a controllable release of anti-cancer drugs up to one month. As a highlight the design of this drug-loaded thermogel significantly slows down tumor growth with intra-tumor sustained release of the chemotherapeutics, which might effectively reduce the non-specific accumulation or toxic effect of the drug on animals at the same time.
This work pioneers injectable PHB thermogels that can be used for the drug delivery to tumors in vivo. The positive results should encourage further development of this thermogel platform as a drug carrier for anti-cancer applications, including on-demand drug delivery and personalized medicine.