title: The encapsulation of bleomycin within chitosan based polymeric vesicles does not alter its biodistribution.
abstract: Polymeric vesicles have recently been developed from an amphiphilic chitosan derivative--palmitoyl glycol chitosan. Their potential as a drug delivery system was evaluated using the anti-cancer compound bleomycin as a model drug. Palmitoyl glycol chitosan (GCP41) was synthesised by conjugation of palmitoyl groups to glycol chitosan. Bleomycin-containing vesicles (669 nm diameter) were prepared from a mixture of GCP41 and cholesterol by remote loading. The vesicles were imaged by freeze-fracture electron microscopy and their in-vitro stability tested. Incubation of the larger vesicles with plasma in-vitro led to a reduction of mean size by 49%, a reaction not seen with control sorbitan monostearate niosomes (215 nm in size). They also showed a higher initial drug release (1 h), but GCP41 and sorbitan monostearate vesicles retained 62% and 63% of the encapsulated drug after 24h, respectively. The biodistribution of smaller vesicles (290 nm) prepared by extrusion through a 200-nm filter was also studied in male Balb/c mice. Encapsulation of bleomycin into polymeric vesicles did not significantly alter the pharmacokinetics of biodistribution of bleomycin in male Balb/c mice although plasma and kidney levels were slightly increased. It is concluded that the extruded GCP41 vesicles break down in plasma in-vivo and hence are unlikely to offer any therapeutic advantage over the free drug.
authors.affiliation: CRC Department of Medical Oncology, University of Glasgow, UK.
authors.forename: J
authors.initials: J
authors.lastname: Sludden
authors.forename: I F
authors.initials: IF
authors.lastname: Uchegbu
authors.forename: A G
authors.initials: AG
authors.lastname: Schätzlein
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics*; D001761:Bleomycin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D010316:Particle Size; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; C114305:palmitoyl glycol chitosan; D001761:Bleomycin; D002686:Chitin; D048271:Chitosan