title: Studies on lactoferrin nanoparticles of gambogic acid for oral delivery.
abstract: OBJECTIVE
  Lactoferrin (Lf), a mammalian cationic iron-binding glycoprotein belonging to the transferrin (Tf) family, has been widely used in a variety of fields ranging from treating infant diarrhea and supporting newborn growth to food and pharmaceutical applications. In this study, Lf nanoparticles were firstly used as carriers of gambogic acid (GA) to enhance oral absorption and anti-cancer activity, hence reducing the related toxic effect.
  
  
  METHODS
  Gambogic acid-lactoferrin nanoparticles (GL-NPs) were prepared by the nanoparticle albumin-bound (NAB) technology. The formed nanoparticles were characterized by DSC, TEM, etc. In situ intestinal perfusion experiment was performed to clarify the absorption mechanism of GL-NPs. Furthermore in vivo and in vitro anti-tumor activities of GL-NPs were also investigated.
  
  
  RESULTS
  GL-NPs was successfully prepared with about 150 nm mean size, +20 mV ζ potential, 92.3 ± 7.2% encapsulation efficiency and 9.04 ± 0.7% DL; GL-NPs also exhibited a better stability and a desirable slow release in vitro experiment. The results of in situ intestinal perfusion showed a transformation of GA absorption from passive diffusion into active transport or facilitated diffusion by GL-NPs. MTT assay of GL-NPs showed almost an equal anti-proliferative effect with arginine solution of GA (Arg-GA) in HepG2 cell. The inhibitory rate against S180 tumor mice after oral administration of GL-NPs was up to 86.01% which was 1.39-folds of intravenous injection of Arg-GA.
  
  
  CONCLUSIONS
  The in vitro results showed that the NAB technology was feasible for industrial production of Lf nanoparticles and the in vivo results proved that the effective GL-NPs is a promising approach for the oral delivery of GA. These obtained research works have also paved the preliminary way for the study of Lf as an oral drug delivery carrier.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
authors.forename: Zhen-Hai
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Xiao-Pan
authors.initials: XP
authors.lastname: Wang
authors.forename: Waddad Y
authors.initials: WY
authors.lastname: Ayman
authors.forename: Were L L
authors.initials: WL
authors.lastname: Munyendo
authors.forename: Hui-Xia
authors.initials: HX
authors.lastname: Lv
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005240:Feasibility Studies; D056945:Hep G2 Cells; D006801:Humans; D007408:Intestinal Absorption; D007781:Lactoferrin / Q000737:chemistry*; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012510:Sarcoma 180 / Q000188:drug therapy; D012995:Solubility; D013499:Surface Properties; D044004:Xanthones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D044004:Xanthones; C052659:gambogic acid; D007781:Lactoferrin