Conjugation of drugs to polyunsaturated fatty acids (PUFAs) has been shown to greatly alter their pharmacokinetic profile, resulting in higher plasma protein binding and slower clearance.  In addition, PUFAs are rapidly taken up by growing tumors and PUFA-drug conjugates exhibit tumor specific accumulation in vitro and in vivo. Next generation taxoids possess a marked increase in activity against multi-drug resistant tumors, and conjugation of these compounds to the PUFAs docosahexaenoic acid (DHA) and a-linolenic acid (LNA) have provided novel anti-cancer agents with greatly improved efficacy. During the course of our preclinical studies on these compounds, their pharmacokinetic profile has been investigated, as well as their cancer cell specificity in vitro. These results, combined with our in vivo efficacy studies and pathological examinations will be presented.

Preclinical evaluation of PUFA conjugates of next generation taxoid SB-T-1214

244th National Meeting (2012)

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