The advantages of cytotoxic drugs such as anthracyclines can be limited by the harmful damage that they inflicted on the human body. One of the main side effects of administering such powerful chemotherapeutic drugs is their negative impact on the cardiovascular system. These adverse side effects can significantly limit the usefulness of freely administered drugs such as doxorubicin. Lower doses must be given for the safety and well being of the patients while ultimately reducing the potency of the drug itself.
Immunoliposomes can allow for the targeted delivery of anthracyclines such as doxorubicin. Specific targeting greatly decreases the detrimental side effects to sensitive tissues outside the targeted site while simultaneously acquiescing a larger dosage of drug at the tumor site without larger doses actually being administered. Immunoliposomes contain reactive lipids on their outer surface that allow for the conjugation of different molecules such as antibodies, peptides, or proteins. The conjugated compounds elicit site-specific delivery of the encapsulated drug.
PEGylated Immunoliposomes contain another layer of dimension. PEGylated Immunoliposomes are coated in reactive PEGylated chains attached to their surface. Antibodies, peptides, or proteins can then be conjugated through the termini of the reactive PEGylated chains. PEGylation allows the Immunoliposome to remain in circulation longer and therefore hone in on the target site more acutely.
A study conducted by Yun-Long Tseng et al. took into consideration the implications of PEGylated Immunoliposomes encapsulating doxorubicin by studying them both in vivo and in vitro. The researchers formulated the immunoliposomes by conjugating them with S5A8 mAB, an anti-idiotype antibody to 38C13 B cell lymphoma or IMN-lipo-dox. These were then compared to plain liposomes also encapsulating doxorubicin (plain lipo-dox) and finally free doxorubicin. The scientists analyzed cellular targeting, uptake, toxicity, and anti-tumor activity.
Results demonstrated that site specific antibody conjugation did in fact work. At 15, 60, and 900 minutes there was a drastically different number of imn-lipo-dox in 38C13 cells as compared to the surrounding tissue. When digging deeper and analyzing the uptake of the cells IMN-lipo-dox were found to deliver doxorubicin 10 times faster than the plain lipo-dox.
Short-term cytotoxicity studies indicated that the imn-lipo-dox reached a 75% growth inhibition for the targeted 38C13 cells while having little to no effect on non targeted tissue. Plain lipo-dox affected 38C13 cells and the surrounding tissue to the same degree. This is because the liposome did not have a way to differentiate the harmful tumor from the healthy tissue.
The researcher next analyzed how each lipid composition reacted in vivo. Mice were incubated with the 38C13 cell line then injected with either plain lipo-dox, IMN-lipo-dox, or free doxorubicin. The mice were observed for their median survival time. Mice injected with IMN-lipo-dox survived 31 days which was significantly longer than mice treated with either plain lipo-dox or free doxorubicin. A separate study conducted in vivo investigated the survival of mice when treatment was altered in 38C13 infected mice. When given two injections of each respective formulation the IMN-lipo-dox mice were most improved increasing their lifespan from 142.3% to 387.5%. Plain lip-dox and free doxorubicin only slightly increased the lifespan of 38C13 infected mice.
Overall, PEGylated immunoliposomes reduced the exposure of non targeted tissue and delivered doxorubicin to the specific targeting site. In addition, due to the site-specific targeting toxicity levels in surrounding tissues were down while anti-tumor activity remained significant.
Copyright by Encapsula NanoSciences 2014
Use this form to find things you need on this site