title: Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model.
abstract: Oral administration of paclitaxel (PTX), a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid) (SMA). Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg) compared to the commercially available PTX formulation (PTX [Ebewe]). In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe). In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer.
authors: Department of Pharmacology and Toxicology.
authors: Neha N
authors: NN
authors: Parayath
authors: Department of Pharmacology and Toxicology.
authors: Hayley
authors: H
authors: Nehoff
authors: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors: Samuel E
authors: SE
authors: Norton
authors: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors: Andrew J
authors: AJ
authors: Highton
authors: Department of Pharmacology and Toxicology; Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA.
authors: Sebastien
authors: S
authors: Taurin
authors: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors: Roslyn A
authors: RA
authors: Kemp
authors: Department of Pharmacology and Toxicology; Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain.
authors: Khaled
authors: K
authors: Greish
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001682:Biological Availability; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D065546:Drug Liberation; D005260:Female; D006801:Humans; D008298:Maleates / Q000737:chemistry*; D020714:Maximum Tolerated Dose; D008807:Mice, Inbred BALB C; D008823:Micelles; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D011137:Polystyrenes / Q000737:chemistry*; D055672:Static Electricity; D018675:Toxicity Tests
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; D008298:Maleates; D008823:Micelles; D011137:Polystyrenes; C024074:styrene-maleic acid polymer; D000410:Alanine Transaminase; D017239:Paclitaxel
keywords: CT-26; HUVEC; antiangiogenic; anticancer nanomedicine; enhanced permeability and retention (EPR) effect; oral delivery