| Popis: |
One of the main challenges in chemotherapy is the delivery of effective doses of cytotoxic agents to the tumor site and simultaneously to minimize the side effects on normal cells. The use of drug delivery systems (DDS) can improve the pharmacological properties of many agents, modifying their pharmacokinetics and biodistribution. Among the DDS available, liposomes are one of the most used and promising. Cytotoxic drug incorporation into liposomes has been reported since 1970. Thanks to their special structure, they are able to encapsulate both hydrophilic and hydrophobic compounds. Today several drugs with various chemical properties (hydrophilic drugs such as N(phosphoacetyl)-L-aspartate or hydrophobic drugs such as doxorubicin) have been succesfully encapsulated into liposomes. Compared to conventional chemotherapeutic drugs (non-encapsulated), the encapsulation of these drugs into liposomes shows several advantages, such as a considerable reduction of side effects associated to conventional chemotherapy, increase of solubility, improvement of therapeutic index and prolonged duration of exposure (Papahadjopoulos, Allen et al., 1991; Drummond, Meyer et al., 1999). Moreover, tumours are one of the primary sites for accumulation of liposomes, where they concentrate due to the higher permeability of the vascular endothelium surrounding tumours. However, despite their unquestionable advantages, unfortunately, liposomes are non site-specific drug delivery systems. Antibody based targeted therapies are the most promising strategies to improve the selectivity and potency of current cancer treatments. The increasing number of new anticancer drugs based on antibodies demonstrates this assumption (Sznol & Holmlund, 1997; Reichert, Rosensweig et al., 2005). However, selectivity provided by the use of antibodies can also be used, not only for direct treatment but to target other anticancer drugs. In this sense, the conjugation of complete or fragmented antibodies to liposomes has resulted in the next generation of drug delivery systems, i.e. immunoliposomes (Park, Hong et al., 1997; Noble, Kirpotin et al., 2004). In this strategy, the liposome acts as a drug carrier, and the antibody allows bringing the drug system specifically to its target. Tumour cells have few specific molecules for recognition as they share many common features with normal cells. Then, the main issue when designing selective immunoliposomes is to find a proper target. Since complete selectivity is hard to achieve, the target must be as selective as possible, i.e. by using tumor-overexpressed proteins as |
