title: Pharmacokinetics and Tissue Disposition of Nanosystem-Entrapped Betulin After Endotracheal Administration to Rats.
abstract: OBJECTIVE
  Betulin is a triterpene extracted from the cork layer of the outer bark of Betula spp. It has a wide spectrum of pharmacological activities, including being lung protective; however, its bioavailability is low. To increase its bioavailability, betulin was entrapped in a nanosystem (BN). In this study, we investigated the pharmacokinetics and tissue distribution of nanosystem-entrapped betulin after single dose endotracheal administration to rats.
  
  
  METHODS
  Betulin was nanosystem-entrapped using a solvent exchange technique. The surface morphology and size of the nanosystem were characterized by transmission electron microscopy and dynamic light scattering. The plasma and tissue concentrations of betulin were determined using a validated high-performance liquid chromatography method.
  
  
  RESULTS
  The highest concentration of betulin was found in lungs and liver, and the lowest in the heart. Betulin did not penetrate highly vascularized tissues or tissue with an average degree of vascularization, nor did it cross the blood-brain barrier. Tissue availability in the lungs was 1.3 times higher for BN than for free betulin. Betulin was detected in the bloodstream at 15 min after administration of BN compared with only at 1 h after administration of free betulin. Penetration of betulin in the liver tissue was characterized by a high degree of intensity both for BN and free betulin. Betulin in the heart tissue was detected in much smaller quantities than in the liver.
  
  
  CONCLUSIONS
  Entrapment of betulin in nanosystem form shows promise as a novel strategy in the treatment of pulmonary diseases.
authors.affiliation: Saint Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P 245, Russia.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Pozharitskaya
authors.affiliation: Saint Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P 245, Russia.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Karlina
authors.affiliation: Saint Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P 245, Russia. spb.pharmacy@gmail.com.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Shikov
authors.affiliation: Saint Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P 245, Russia.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kosman
authors.affiliation: Saint Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P 245, Russia.
authors.forename: Valery G
authors.initials: VG
authors.lastname: Makarov
authors.affiliation: Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity (3rd Floor), Tykistökatu 6A, 20520, Turku, Finland.
authors.forename: Eudald
authors.initials: E
authors.lastname: Casals
authors.affiliation: Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity (3rd Floor), Tykistökatu 6A, 20520, Turku, Finland.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosenholm
mesh_terms: D000818:Animals; D029662:Betula / Q000737:chemistry*; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D007442:Intubation, Intratracheal; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution; D014315:Triterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000094062:Betulinic Acid
chemical_list: D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid