Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations.

Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations. Drug Deliv. 2018 Nov;25(1):1546-1559 Authors: Zhou Y, Li N, Qiu Z, Lu X, Fang M, Chen X, Ren L, Wang G, Ouyang P Abstract Triacontanol (TA, C30H62O), abundantly present in plant cuticle waxes and bee waxes, has been found to display promising anti-neoplastic potentials. As a long chain fatty alcohol, TA possesses limited aqueous solubility, which hinders its medicinal application. To overcome its solubility barrier, a polymer prodrug was synthesized through attaching TA to poly ethylene glycol (PEG), using succinic acid as a linker with bifunctional amide and ester bonds. Anti-neoplastic effects of PEG-TA were assessed in LoVo and MCF7 cells, anti-proliferative and apoptosis-inducing activities were subsequently confirmed in mouse xenograft model. Encouragingly, PEG-TA possessed selective anti-cancer ability. It did not exhibit significant cytotoxicity on normal cells. Mechanistic examination revealed inhibition of NF-κB nuclear translocation, suppression on matrix degradation enzyme and down-regulation of angiogenic signaling might contribute to its anti-malignant effects. Pharmacokinetics clearly indicated PEGylated TA (named as mPEG2K-SA-TA) substantially enhanced TA delivery with increased plasma exposure (19,791 vs. 336.25 ng·mL-1·h-1, p < .001), mean residence time (8.46 vs. 2.95 h, p <â€...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research