title: N-octyl-N-arginine-chitosan (OACS) micelles for gambogic acid oral delivery: preparation, characterization and its study on in situ intestinal perfusion.
abstract: BACKGROUND
  Gambogic acid (GA) can inhibit the growth of various cancer cells. However, the low bioavailability caused by insolubility, limits its clinical application. L-arginine is always used with GA to form a complex to obtain the higher solubility. Moreover, guanidyl group from arginine, which can facilitate the cellular uptake, was identified.
  
  
  OBJECTIVE
  In this study, L-arginine and chitosan (CS) were used for the first time to prepare N-octyl-N-arginine CS (OACS), a novel amphiphilic carrier for GA with solubility- and absorption-enhancing functions; the characterization of the GA loaded OACS micelles (GA-OACS) and its absorption-enhancing effect were also investigated.
  
  
  METHODS
  GA-OACS were prepared by the dialysis method. The formed micelles were characterized and evaluated by atomic force microscope (AFM), dynamic light scattering, differential scanning calorimeter (DSC), solubility test, in vitro release and in situ intestinal perfusion.
  
  
  RESULTS
  The GA-OACS micelles were successfully prepared attaining a 35.3% drug loading and 82.2% entrapment efficiency. GA-OACS had a homogeneous particle size of 160.3 nm; +21.8 mv zeta potential with smooth continuous surface was observed by using AFM. DSC diagram suggested that GA was encapsulated in the micelles. Meanwhile, GA encapsulated in micelles exhibited a desirable slow release in vitro experiment. The solubility of GA in OACS micelles was increased up to 3.16 ± 0.13 mg/mL, 2320 times than that of free GA. The single pass perfusion showed that the absorption of GA-OACS micelles was enhanced 3.6-fold, 2.1-fold and 2.2-fold for jejunum, ileum and colon, respectively.
  
  
  CONCLUSIONS
  OACS provided excellent ability of drug loading, increasing solubility and enhanced absorption for GA, which indicated that OACS micelles as an oral drug delivery carrier may have potential research and application values.
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing , China .
authors.forename: Fan
authors.initials: F
authors.lastname: Yu
authors.forename: Chenghua
authors.initials: C
authors.lastname: He
authors.forename: Ayman Y
authors.initials: AY
authors.lastname: Waddad
authors.forename: Were L L
authors.initials: WL
authors.lastname: Munyendo
authors.forename: Huixia
authors.initials: H
authors.lastname: Lv
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D008516:Medicine, Chinese Traditional; D008823:Micelles; D015394:Molecular Structure; D010477:Perfusion; D010539:Permeability; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D044004:Xanthones / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; C581649:N-octyl-N-Arginine chitosan; D044004:Xanthones; C052659:gambogic acid; D048271:Chitosan; D001120:Arginine
keywords: Absorption enhancer; N-octyl-N-arginine-chitosan; arginine; gambogic acid; micelle