Lipophilicity long-term effects

Lipophilic hormones The principle mode of action for Upophitic hormones is to penetrate cells where they interact with the intracellular receptors, which mediate their long-term effects. These in turn penetrate the nucleus to provoke specific mRNA synthesis by binding to promoter elements on DNA. Steroid hormones (e.g. glucocorticoids, androgens, estrogens, progestins) and thyroxine. 

Little is also known of the long term renal effects of chronic low dose exposure to pesticides. Chronic exposure to the now banned dichlorodiphenyl-trichloroethane (DDT), a lipophilic compound with prolonged body fat retention, has been associated with renal injury [105]. 

Dexamethasone alcohol and triamcinolone acetonide have been studied in PVR animal models (30-33). These agents are particularly suited for local delivery as they are both relatively lipophilic, and therefore, may be administered as a suspension. The crystalline drug then acts as a depot, providing relatively long-term intraocular levels of steroid that can be given at high doses without apparent retinal toxicity (33). While direct delivery of corticosteroids has been demonstrated to be both safe and effective in the treatment of PVR, few studies have been performed in humans (31,32). 

Toxicity Dimercaprol causes a high incidence of adverse effects, possibly because it is very lipophilic and readily enters cells. Its toxicity includes transient hypertension, tachycardia, headache, nausea and vomiting, paresthesias, and fever (especially in children). It may cause pain and hematomas at the injection site. Long-term use is associated with thrombocytopenia and increased prothrombin time. 

Similar thermosensitive poly(organo)phosphazenes have also been assessed in combination with camptothecin [178], 5-fluorouracil [179] and silibinin [180], as well as the breast cancer drug 2-m ethoxy estradiol [181], thus proving to be a versatile, effective and safe delivery system. Furthermore, as well as the delivery of standard, lipophilic chemotherapeutic agents, the approach has been extended to other, noncancer therapies, for example, injectable polyplex hydrogels for the localised and long-term delivery of siRNA (discussed in Section 3.2.2) and growth hormone delivery. 

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