Influence of drug-to-lipid ratio on drug release properties and liposome integrity in liposomal doxorubicin formulations
2008 (English)In: Journal of liposome research, ISSN 0898-2104, Vol. 18, no 2, 145-157 p.Article in journal (Refereed) Published
Recent studies have shown that the release properties of vincristine encapsulated in large unilamellar vesicles (LUV) can be regulated by varying the drug-to-lipid (D/L) ratio. In this work it is shown that the drug-to-lipid ratio technique for regulating drug release also applies to doxorubicin encapsulated in LUV. In particular it is shown that the half-times (T1/2) for doxorubicin release from distearoylphosphatidylcholine (DSPC)/cholesterol LUV in vitro can be increased more than six-fold by increasing the D/L ratio from 0.05 (wt/wt) to 0.39 (wt/wt). This behavior is consistent with the behavior expected for drugs that ppt. following accumulation into liposomes. It is shown that the release properties of ciprofloxacin-a drug that does not ppt. following accumulation into LUV-are not affected by the D/L ratio. It is also shown that the cryst. intravesicular doxorubicin ppts. obsd. as the D/L ratio is raised from 0.05 to 0.46 adopt increasingly unusual morphologies. Linear crystals are obsd. at lower D/L values, however triangular and rectangular variations are obsd. as the D/L ratio is increased, and induce considerable distortion in vesicle morphol. It is noted that trapping efficiency following uptake of external doxorubicin into LUV is reduced from nearly 100% at a D/L ratio of 0.05 (wt/wt) to less than 70% at an (initial) D/L ratio of 0.8 (wt/wt). It is suggested that this arises, at least in part, from membrane-disrupting effects of internal drug crystals as they increase in size.
Place, publisher, year, edition, pages
2008. Vol. 18, no 2, 145-157 p.
liposomes, drug precipitation, liposoml doxorubicin, drug loading
IdentifiersURN: urn:nbn:se:uu:diva-17541DOI: 10.1080/08982100802129372ISI: 000257020500004PubMedID: 18569449OAI: oai:DiVA.org:uu-17541DiVA: diva2:45312