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In Vitro and In Vivo Studies Involving Liposomes

In 2005 Hao et al. [48] studied the efficiency of liposomes in delivering an anticancer drug topotecan (TPT) to the tumors. They compared the efficiency of S-liposomes and H-liposomes, which comprised soybean phosphatidylcholine and hydrogenated

Distribution of topotecan (TPT) in tumor tissue following a single intravenous dose [48]. (Reprinted with permission.)

Figure 6.5 Distribution of topotecan (TPT) in tumor tissue following a single intravenous dose [48]. (Reprinted with permission.)

Nanoparticulate Systems for Therapeutic and Diagnostic Applications 113

soybean phosphatidylcholine, respectively. Fig. 6.5 shows the results obtained by Hao et al., which clearly indicate the high tumor concentration of TPT delivered using the H-liposomes compared with the free drug and S-liposomes.

In another study, Wei et al. [49] studied the biodistribution of gadolinium-diethylene triamine penta-acetate (DTPA) [a magnetic resonance imaging (MRI) contrast agent] encapsulated in paramagnetic liposomes in A549 tumor-bearing mice (Fig. 6.6).

Biodistribution of Gd-DTPA encapsulated in paramagnetic liposomes in A549 tumorbearing mice [49]

Figure 6.6 Biodistribution of Gd-DTPA encapsulated in paramagnetic liposomes in A549 tumorbearing mice [49]. Gd-DTPA, gadolinium-diethylene triamine penta-acetate;N-Gd-LP, nontargeted paramagnetic liposomes;RGD-Gd-LP, arginine-glycine-aspartic coupled paramagnetic liposomes. (Reprinted with permission.)

They compared the biodistribution of pure Gd-DTPA (Gd-DTPA), nontargeted (N-Gd-Lp), and arginine-glycine-aspartic acid (RGD) coupled (RGD-Gd-LP) paramagnetic liposomes. As expected, the liposomal formulations led to significant improvements in the biodistribution of Gd-DTPA.

Challenges Associated With Liposomes

The major problems faced by liposomal formulations include limited long-term stability, difficulties with large-scale production, and rapid elimination by the MPS system as described earlier in this chapter. The stability issues can usually be addressed by freezedrying the liposomes at low pressure using cryoprotectants such as trehalose. The rapid elimination from the circulation can be thwarted by coating the liposomes with polymers such as polyethylene glycol and chitin derivatives [50]. Such liposomes are commonly referred to as stealth liposomes and they display high retention time in circulation, which ultimately helps in increasing the drug concentration at the site of action [51]. Other problems with liposomal formulations include low encapsulation efficiency, rapid leakage of water-soluble drugs, and other formulation design and manufacturing problems.

 
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