ISSN:
1573-904X
Keywords:
superoxide dismutase
;
long circulating liposomes
;
subcutaneous administration
;
therapeutic activity
;
biodistribution
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. We are exploring liposomal delivery with the aim to changethe pharmacokinetics and biodistribution of SOD to increase itstherapeutic activity. From a practical point of view, a convenient route ofadministration would be the subcutaneous (s.c.) route. Liposomal sizehas been shown to be the most important factor influencing the rateand extent of drainage of liposomes from the s.c. injection site. Methods. To monitor the in vivo fate of the subcutaneous administeredSOD-containing liposomes in rats with a chronic arthritis inflammation,the liposomes were labeled by the co-encapsulation of the111In-DTPA complex in the internal water space. Results. Over the initial 10h-observation period post-injection, thesmall-sized poly(ethyleneglycol)-liposomes (mean size about 110 nm)left the site of injection to a 2-fold higher extent (45% of the injecteddose) as compared to large-sized poly(ethyleneglycol)-liposomes(mean size about 450 nm). Small-sized liposomes gave a 17-fold higheruptake in the inflamed foot than the large-sized liposomes. Comparingthe localization in the inflamed foot with the non-inflamed foot, uptakewas more than 15-fold higher for the small-sized liposomes ascompared to the large-sized liposomes. After s.c. administration,small-sized SOD-liposomes showed substantial higher activity thanlarge-sized SOD-liposomes. S.C. administration of small-sizedSOD-liposomes is equally effective as i.v. administration of the same liposomes.I.V. administration of the large-sized SOD-liposomes yielded asignificantly higher activity as compared to s.c. administration. Conclusions. These results indicate that small-sized poly(ethyleneglycol)-liposomes can be used for the targeting of SOD to arthritic sitesafter subcutaneous administration.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007577101964
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