Cardiac Protection with Targeted Drug Delivery to Ischemic-Reperfused Myocardium

Abstract

The concept of targeted drug delivery implies selective accumulation of the drug in the tissue affected by the pathological process after systemic administration of the drug and its carrier with minimal effect of the former on the intact organs and tissues (Lammers et al., 2010). The idea of targeted delivery has been first suggested by Paul Erhlich in 1906 when he introduced the concept of «magic bullet» which is directed against target cells only without any damage to healthy tissue (Erhlich, 1906). In the current medical practice, most of the drugs are administered orally or parenterally, resulting in natural biodistribution and systemic effect on the organism. This type of distribution is justified for the drugs which act on the systemic mechanisms of disease development and progression. At the same time, in case of focal pathological processes such as tumor growth, inflammation and ischemia it may be more clinically attractive to ensure the local rise in the drug concentration within the pathological area thus avoiding the putative side effects on neighboring tissues. This point can be illustrated by several examples. It is known that the administration of antitumor drug doxorubicin is associated with severe cardiomyopathy, suppression of myeloand megakaryopoiesis, nausea, vomiting, and development of alopecia (Carvalho et al., 2009). Encapsulation of doxorubicin into liposomes resulted in dramatic reduction of these doselimiting side effects (Leonard et al., 2009). The implementation of site-specific drug delivery may also benefit female patients receiving estrogens for treatment of osteoporosis. Along with desirable effect on the bone, estrogens may cause some unwanted effects, especially increased risk of uterine bleeding and development of endometrial cancer (Romer, 2006). One might suggest that bone-targeted delivery of estrogens will decrease the probability of these side effects. The application of nano-sized particles for drug transport may offer a new means of delivering drugs selectively into the affected tissue.