Injectable rapidly dissolving needle-type gelatin implant capable of delivering high concentrations of H2O2 through intratumoral injection

• Published in: Biomedicine & pharmacotherapy Vol. 156; p. 113910
• Main Authors: Park, Sewon, Kim, Jungyu, Lee, Changkyu
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.12.2022; Elsevier
• Subjects: Gelatin; Glucose oxidase; Hydrogen peroxide generation; Implant; Intratumoral drug administration; Starch; Glucose oxidase; Intratumoral drug administration; Implant; Starch; Gelatin; Hydrogen peroxide generation; H2O2; GOD; TME; ECM
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113910

Intratumoral injections can reduce systemic absorption and deliver large amounts of drugs to the tumor, thereby reducing side effects and exhibiting high therapeutic efficacy. Therefore, a variety of drug delivery systems, such as hydrogels, fine particles, and nanoparticles, have been studied. Although the sustained-release drug delivery system can effectively reduce systemic absorption due to the slow release of the drug from the site of intratumoral injection, it lacks the ability to deliver high concentrations of drugs to the tumor. In particular, the larger the tumor size, the lower the efficacy of the treatment. To address this problem, this study focused on the tumor structure. Owing to the three-dimensional structure of the dense tumor microenvironment (TME) and abnormal blood vessels, drugs administered directly into the tumor act as if they were encapsulated in a hydrogel. To evaluate whether the three-dimensional structure of the tumor affects the intratumoral distribution and systemic absorption of drugs, needle-type starch implants (GOD-NS implants) and needle-type gelatin implants (GOD-NG implants) containing glucose oxidase (GOD), a protein that exhibits anti-cancer effects through hydrogen peroxide (H2O2) generation, were prepared. Both GOD-NS and GOD-NG implants can be easily injected into tumors. GOD-NS implants released GOD slowly, whereas GOD-NG implants released most of the GOD within 1 h. When a GOD-NG implant that rapidly released GOD was also injected, a high concentration of GOD was maintained in the tumor for a long time as it was trapped in the three-dimensional structure of the tumor. This study demonstrated that intratumoral injection of a rapidly drug-releasing gelatin needle may be a novel drug delivery system capable of long-term retention of high drug concentrations in tumors, as the three-dimensional structure of the tumor affects drug delivery. ••High-dose drug administration may cause toxicity due to systemic absorption.•The tumor's dense ECM and abnormal blood vessels can act as a barrier to drug leakage.•Rapidly-dissolving NG implants can deliver higher concentrations of drugs to the tumor.