title: Human serum albumin conjugates of 7-ethyl-10-hydroxycamptothecin (SN38) for cancer treatment.
abstract: SN38 (7-ethyl-10-hydroxy-comptothecin) is a potent metabolite of irinotecan, which has been approved for treatment of metastatic colorectal cancer. Considering the notable potency of SN38, it has been introduced as an anticancer candidate. In this study, human serum albumin (HSA) conjugates of SN38 were formulated to overcome the solubility problem beside improving the active form stability and tumor tissue targeting. In this target, two different molar ratios of conjugates (SN38 : HSA 15 : 1 and 60 : 1) were prepared by derivatization of 20-hydroxyl group of SN38 with glycine, followed by addition of succinyl group to glycine through which HSA was covalently attached. The conjugates with particle size of about 100 nm revealed enhanced water solubility and were relatively stable in neutral and acidic solutions. For SN38-HSA-15 and SN38-HSA-60 IC50 values were compared with irinotecan in HT-29 human colon cancer cells. Furthermore, biodistribution studies of SN38-HSA conjugate resulted in proper blood concentration level within 4 h. Moreover, blood cytotoxicity assay revealed no toxicity effect on liver and spleen. Collectively, our present investigation offers a water-soluble form of SN38 attached to HSA and suggests using favorable properties as a promising anticancer agent for further preclinical and clinical investigations.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nano Alvand Co., Avicenna Tech. Park, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Sepehri
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nano Alvand Co., Avicenna Tech. Park, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hasti
authors.initials: H
authors.lastname: Rouhani
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Ahmad Reza
authors.identifier: 0000-0001-9441-8333
authors.initials: AR
authors.lastname: Ghanbarpour
authors.affiliation: Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Gharghabi
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Faranak
authors.initials: F
authors.lastname: Tavassolian
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.affiliation: Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.identifier: 0000-0001-5051-6214
authors.initials: MH
authors.lastname: Ghahremani
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Rassoul
authors.identifier: 0000-0003-0694-7556
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D055672:Static Electricity; D014018:Tissue Distribution
chemical_list: D012709:Serum Albumin; D000077146:Irinotecan; D002166:Camptothecin