title: Polypeptide-based Micelles for Delivery of Irinotecan: Physicochemical and In vivo Characterization.
abstract: OBJECTIVE
  Irinotecan (IRI) is a broad spectrum chemotherapeutic agent used individually or in combination to treat multiple malignancies. Present study aimed at developing polypeptide-based block ionomer complex (BIC) micelles to improve the pharmacokinetic and antitumor response of IRI.
  
  
  METHODS
  Irinotecan-loaded BIC micelles (IRI-BIC) was prepared and evaluated in terms of various physicochemical and biological parameters including size, shape, release, cytotoxicity, and pharmacokinetic analysis. In vivo antitumor efficacy was investigated in SCC-7 bearing xenograft tumor model.
  
  
  RESULTS
  IRI was successfully incorporated into the ionic cores of poly(ethylene glycol)-b-poly(aspartic acid) (PEG-b-PAA) with a high drug loading capacity (~80%). The electrostatically assembled BIC micelles were nanosized (~50 nm) with uniform size distribution pattern (PDI~0.1). The BIC micelles exhibited pH-sensitiveness with limited release of IRI at physiological conditions and significantly enhanced the release rate at acidic conditions, making it an ideal delivery system for tumor targeting. The IRI-BIC showed a dose-dependent cytotoxicity in SCC-7 and A-549 cancer cell lines. Pharmacokinetic studies clearly showed that BIC micelles improved the IRI blood circulation time and decreased its elimination rate constant, while that of free IRI, rapidly eliminated from the central compartment. Moreover, IRI-BIC showed superior therapeutic performance with no toxicity in BALB/c nude xenograft mice. The micelle treated group showed an inhibition rate of ~66% compared to free IRI treated group.
  
  
  CONCLUSIONS
  Taken together, BIC micelles could be a potentially useful nanovehicle with promising applicability in systemic tumor treatment.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan, 712-749, South Korea.
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Choi
authors.forename: Hyuk Jun
authors.initials: HJ
authors.lastname: Cho
authors.forename: Subbaih Kandasamy
authors.initials: SK
authors.lastname: Umadevi
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006801:Humans; D000077146:Irinotecan; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; C493635:polyethylene glycol-block-polyaspartic acid; D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin