Cytotoxic drug compounds

Safer handling of highly potent or cytotoxic drug compounds. 

The advantageous effects of liposomal carrier systems include protection of compounds from metabolism or degradation, as well as enhanced cellular uptake. Liposome-mediated delivery of cytotoxic drugs to cells in culture has resulted in improved potency [58,59]. Prolonged release of encapsulated cargo has also been demonstrated [60,61]. More recently, liposomes with extended circulation half-lives and dose-independent pharmacokinetics (Stealth liposomes) [62] have shown promise in delivery of drugs that are normally very rapidly degraded. 

Multidrug resistance (MDR) is the name ascribed to the phenomenon whereby cancer cells and tumors develop resistance to chemotherapeutic agents. Conceptually, this can be viewed as a survival response whereby cancer cells endeavor to ward off cytotoxic compounds. Mechanistically, MDR is typically mediated by overexpression of P-glycoprotein (P-gp aka ABCB1) or other plasma membrane ATPases that export cytotoxic drugs used in chemotherapy, thereby reducing their efficacy. 

Compared to small molecules, barrier opening for high molecular weight compounds is of shorter duration [72]. Furthermore, a characteristic difference exists in the degree of barrier opening in tumour versus normal brain tissue. Barrier disruption was consistently found to be more pronounced for the normal BBB, which may limit the clinical applicability of hyperosmolar barrier opening, at least for cytotoxic drugs [76]. 

Bi-functional antibodies can also be obtained from the fusion of natural antibodies or recombinant antibodies with compounds that might carry out auxiliary functions after antibody binding to its specific target (Hudson and Souriau, 2003 Roque et al., 2004). These compounds can be radioactive conjugates, cytotoxic drugs, proteins, toxins, enzymes, and viruses, any of which can have diagnostic or therapeutic uses. 

ANTICANCER AND IMMUNOMODULATING DRUGS CYTOTOXICS Platinum compounds-carboplatin, cisplatin, oxaliplatin... 

Busulfan is a potent cytotoxic drug. Early in development of the compound, in vivo experiments indicated that busulfan caused severe depression in the bone marrow. The most prevalent acute toxic effects associated with busulfan in animals are severe pancytopenia from bone marrow failure. Associated in vivo experiments show bone marrow aplasia, stromal cell damage, immunosuppression (impaired T-lymph-ocyte function), and pronounced adverse effects on reproductive glands, germ cells, and fertility in animals (lowest effective dose tested was 2 mg kg... 

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