title: Delivering instilled hydrophobic drug to the bladder by a cationic nanoparticle and thermo-sensitive hydrogel composite system.
abstract: Some bladder disease therapies can benefit from intravesical drug delivery, which involves direct instillation of drug into the bladder via a catheter, to attain high local concentrations of the drug with minimal systemic effects. Deguelin is a potential anticancer agent, however, its poor water solubility and neurotoxicity restrict its clinical application. To address these challenges, we investigated the promising application of deguelin in the intravesical therapy of bladder cancer by designing a novel intravesical drug delivery system for deguelin. It was found that deguelin could efficiently kill bladder cancer cells and inhibit angiogenesis. Intravesically administrated deguelin had better tolerance than systemically applied deguelin. Encapsulation of deguelin in cationic DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) hybrid nanoparticles (DMP) created the deguelin loaded DMP nanoparticles (D/DMP). They had a mean particle size of 35 nm and zeta potential of 21 mV, rendering deguelin completely dispersible in aqueous media. Encapsulation of deguelin in cationic DMP nanoparticles enhanced the anticancer activity of deguelin in vitro. In addition, D/DMP nanoparticles were incorporated into a thermo-sensitive Pluronic F127 hydrogel, forming a novel D/DMP-F system, which remained in a flowing liquid state at lower than 25 °C, but underwent gelation at higher temperatures. The DMP nanoparticles in the F127 hydrogel system (DMP-F) could significantly extend the hydrophobic drug residence time and increase the drug concentration within the bladder. These results suggested that DMP-F was a good intravesical drug delivery system and D/DMP-F may have promising applications in intravesical therapy of bladder cancer.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Men
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: XingMei
authors.initials: X
authors.lastname: Duan
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: MaLing
authors.initials: M
authors.lastname: Gou
authors.forename: XiaWei
authors.initials: X
authors.lastname: Wei
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: BiLan
authors.initials: B
authors.lastname: Wang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Du
authors.forename: MeiJuan
authors.initials: M
authors.lastname: Huang
authors.forename: LiJuan
authors.initials: L
authors.lastname: Chen
authors.forename: ZhiYong
authors.initials: Z
authors.lastname: Qian
authors.forename: YuQuan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010316:Particle Size; D012402:Rotenone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013696:Temperature; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D004337:Drug Carriers; D012402:Rotenone; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C107676:deguelin