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.

Chitosan derivatives obtained by chemical modifications for biomedical and environmental applications

“…A water-soluble N-methylene phosphonic chitosan (NMPC) was also synthesized using chitosan, phosphorous acid and formaldehyde [59]. A simple methodology for the preparation of a new chitosan derivative surfactant, N-lauryl-N-methylene phosphonic chitosan (LMPC), has been developed [60] (Fig. 5).…”

Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement

“…Finally, physically cross-linked hydrogels can be obtained by hydrophobic modifi cation of polymers and in particular of polysaccharides such as chitosan, dextran, pullulan, and carboxymethyl curdlan (Noble et al 1999 ;Sludden et al 2000 ;Cerchiara et al 2002 ). Glycol chitosan substituted with palmitoyl chains is an example of a hydrophobized polysaccharide.…”

Vesicles Prepared from Synthetic Amphiphiles — Polymeric Vesicles and Niosomes

“…1120 However, clearly the energy required for self assembly is not trivial as vesicles are not easily formed by hand shaking, unlike low molecular weight surfactant formulations. 4 Vesicles once formed are morphologically stable for months 11 and may be loaded with hydrophilic [43][44][45] and hydrophobic [see Fig. 6(b) below] solutes, by probe sonicating in the presence of such solutes.…”