Introduction:

Global improvement of health care and living conditions has led to an increase of the elderly population. Along with aging, comes increasing number and frequency of diseases, including cancer. Aging is also associated with reduced intestinal motility, lower muscle mass, changes in total body water and fat content, and impaired hepatic and renal function, which lead to modified drug pharmacokinetics, in addition to potentially altered pharmacodynamics. The net effect of these changes on response to specific drugs is difficult to predict and needs be addressed on a drug-to-drug and individual-to-individual basis.

Objective:

To determine the effect of age on the accumulation and therapeutic efficacy of Doxil-like PEGylated liposomal doxorubicin (PLD) in mice bearing extra-hepatic tumors.

Methods:

“Young” (4-5 week old) and “Old” (1.5 year old) nude Hsd athymic mice were injected subcutaneously with Daoy human medulloblastoma cells. Mice of each age group were divided into 4 cohorts: control (no treatment), PLD, radiofrequency ablation therapy (RFA), and combined PLD+RFA. Mice were followed over 150 days. PLD distribution was determined by near-infrared imaging with indocyanine green (ICG)-labeled PEGylated nano-liposomes (ICG-SUV) similar to Doxil. The level of ICG transfer from donor ICG-SUV to ICG-free acceptor liposomes was an indicator of the association integrity of ICG with the liposomes

Results:

Tumor growth rate was higher and survival was lower in old versus young mice (p<0.05). Likewise, tumors in old mice were less susceptible to either PLD or RFA monotherapy. Nevertheless, PLD combined with RFA therapy succeeded to eliminate the age-related differences in anti-cancer treatment effectiveness (p>0.05). ICG-SUV emission suggested preferable liposomal accumulation in tumors of young mice compared to old mice.

Conclusion:

Old and young mice bearing medullablastoma xenografts differ in both, cancer progression and the outcomes of treatment. This finding of age influence may also have impact on treatment success with other nano-liposomal chemotherapeutic drugs’ formulations. The poor outcome of PLD treatment alone in old mice is partially explained by lower tumor accumulation of doxorubicin liposomes.

^_Reference:

^{_{Andrianov AV et al., Therapeutic Efficacy of Combined PEGylated Liposomal Doxorubicin and Radiofrequency Ablation: Comparing Single and Combined therapy on Young and Old Mice. J Control Release, 2017; 257:2-9.}}