Abstract
(1) Background: doxorubicin is a potent chemotherapeutic agent, but it has limitations regarding its side effects and therapy resistance. Hydrogels potentially deal with these problems, but several characterizations need to be optimized to better understand how hydrogel assisted chemotherapy works. Poloxamer 407 (P407) hydrogels were mixed with doxorubicin and physico-chemical, biological, and pharmacological characterizations were considered. (2) Methods: hydrogels were prepared by mixing P407 in PBS at 4 °C. Doxorubicin was added upon solutions became clear. Time-to-gelation, hydrogel morphology, and micelles were studied first. The effects of P407-doxorubicin were evaluated on MC-38 colon cancer cells. Furthermore, doxorubicin release was assessed and contrasted with non-invasive in vivo whole body fluorescence imaging. (3) Results: 25% P407 had favorable gelation properties with pore sizes of 30–180 µm. P407 micelles were approximately 5 nm in size. Doxorubicin was fully released in vitro from 25% P407 hydrogel within 120 h. Furthermore, P407 micelles strongly enhanced the anti-neoplastic effects of doxorubicin on MC-38 cells. In vivo fluorescence imaging revealed that hydrogels retained fluorescence signals at the injection site for 168 h. (4) Conclusions: non-invasive imaging showed how P407 gels retained drug at the injection site. Doxorubicin P407 micelles strongly enhanced the anti-tumor effects.
Highlights
Doxorubicin is an anti-neoplastic drug that belongs to the anthracycline family of medication.Its mode of action relies on the binding to DNA via intercalation, which results in cessation of proliferation and induction of cell apoptosis [1]
Poloxamer 407 (P407) hydrogels appear as fluid when kept below the gelation temperature
The time that it takes for hydrogels to convert into the solid state is referred to as time-to-gelation, which is among others dependent on P407 concentration [10]
Summary
Doxorubicin is an anti-neoplastic drug that belongs to the anthracycline family of medication.Its mode of action relies on the binding to DNA via intercalation, which results in cessation of proliferation and induction of cell apoptosis [1]. Problems related to drug resistance and systemic side effects, in particular, cardiotoxicity, can substantially narrow the application of doxorubicin [4]. These drawbacks warrant, in particular, the optimization of doxorubicin delivery. Injectable in situ gelling systems that are based on biodegradable polymers represent promising drug delivery platforms for coping with these hurdles. Owing to their promising effects on sustained drug release, various types of polymeric hydrogels have gained considerable interest for the optimization of drug delivery [5,6,7,8,9]. P407 injectable hydrogels bear various favorable features as delivery system, including biocompatibility, non-invasive and easy administration, promotion of sustained drug release, and increasing therapeutic efficacy [10,11]
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