title: Improving Anti-Tumor Activity of Curcumin by Polymeric Micelles in Thermosensitive Hydrogel System in Colorectal Peritoneal Carcinomatosis Model.
abstract: In this work, we prepared an in situ gel-forming composite drug delivery system (DDS) to treat colorectal peritoneal carcinomatosis. The composite DDS was based on curcumin loaded polymeric micelles (Cur-M) and thermosensitive hydrogel. Cur-M had a particle size of 27.1 ± 1.3 nm with polydisperse index of 0.149 ± 0.017, and the drug loading and encapsulation efficiency of Cur-M were 14.82 ± 0.07 and 98.83 ± 0.45%, respectively. The prepared Cur-M in thermosensitive hydrogel system (Cur-H) was a free-flowing sol at ambient temperature, and converted into non-flowing gel at body temperature, serving as a drug depot. In vitro drug release behavior suggested that Cur-H and Cur-M could release Cur in an extent period, and Cur-H showed a slower cumulative release rate. In addition, compared with free Cur, Cur-M showed higher cytotoxicity and apoptotic induction efficiency. Furthermore, colorectal peritoneal carcinomatosis mouse model was used to evaluate the anti-tumor activity of Cur-H, and the results suggested that Cur-H could inhibit tumor growth and metastasis, and prolonged survival of tumor-bearing mice. Immunohistochemical and immunofluorescent staining of tumor tissues in each group were conducted. The results demonstrated that tumors in Cur-H group showed lower proliferation activity, more apoptotic cells, and fewer microvessels. Besides, pharmacokinetic studies of Cur-H and Cur-M by intraperitoneal administration were performed. Compared with Cur-M, Cur-H showed a higher AUC and longer t½. Thus, the above results suggested that Cur-H may have potential applications in colorectal peritoneal carcinomatosis.
authors: Wenli
authors: W
authors: Zhang
authors: Tao
authors: T
authors: Cui
authors: Lei
authors: L
authors: Liu
authors: Qinjie
authors: Q
authors: Wu
authors: Lu
authors: L
authors: Sun
authors: Ling
authors: L
authors: Li
authors: Ning
authors: N
authors: Wang
authors: Changyang
authors: C
authors: Gong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis*; D004058:Diffusion; D004357:Drug Synergism; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D013696:Temperature; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008823:Micelles; D053769:Nanocapsules; D003474:Curcumin