title: In vivo efficacy of an intratumorally injected in situ-forming doxorubicin/poly(ethylene glycol)-b-polycaprolactone diblock copolymer.
abstract: The effectiveness of systemically administered anticancer treatments is limited by difficulties in achieving therapeutic doses within tumors, a problem that is complicated by dose-limiting side effects to normal tissue. This work examined injectable in situ-forming gels as a localized drug-delivery system. An MPEG-PCL (MP) solution containing doxorubicin (Dox) existed in an emulsion-sol state at room temperature and rapidly gelled in vitro and in vivo at body temperature. The release of Dox from Dox-loaded MP gels was sustained in vitro over 20 days after an initial burst, indicating that the MP gel acted as a drug depot. Dox-loaded MP gels exhibited remarkable in vitro anti-proliferative activities against B16F10 cancer cells. In vivo experiments employing B16F10 cancer cell xenograft-bearing mice showed that a single intratumoral injection of Dox-loaded MP gel inhibited the growth of tumors as effectively as repeated injections of free Dox, and more effectively than a single dose of free Dox, or saline or gel alone. Consistent with the observed suppression of tumor growth, intratumorally injected free Dox or Dox released from Dox-loaded MP gels caused apoptosis of tumor cells. The tumor biodistribution of free Dox after 1 day was ∼90%, which dropped to ∼15% after 4 days. The biodistribution of Dox following a single injection of Dox-loaded MP gel was also ∼90% on day 1, but remained at ∼13%, even after 15 days. Only a small amount of Dox was found in other organ tissues following intratumoral injection, implying fewer off-target side effects.
authors: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors: Yun Mi
authors: YM
authors: Kang
authors: Gyeong Hae
authors: GH
authors: Kim
authors: Jae Il
authors: JI
authors: Kim
authors: Da Yeon
authors: DY
authors: Kim
authors: Bit Na
authors: BN
authors: Lee
authors: So Mi
authors: SM
authors: Yoon
authors: Jae Ho
authors: JH
authors: Kim
authors: Moon Suk
authors: MS
authors: Kim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005782:Gels / Q000737:chemistry*; D006801:Humans; D007267:Injections; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D004337:Drug Carriers; D005782:Gels; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D011092:Polyethylene Glycols; D004317:Doxorubicin