Abstract
In the present paper we describe the synthesis and toxicity studies of well-defined tailor made oligo-[ R, S]-3-hydroxybutyrates (OHBs). The results indicate potential applicability of these nano-polymers as drug delivery carriers. Several OHBs of number average molecular weight ( M n) ranging from 800 to 2400 have been synthesized and tested on transformed hamster V79 fibroblasts and murine melanoma B16(F10) cells using the 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) based drug resistance and clonogenic survival assays. We show that 96-h incubation of cells with 1–9 μg/ml of OHBs did not affect cell viability. Incubation of OHBs with rat hepatoma FTO-2B cells stably transfected with chloramphenicol acetyltransferase (CAT) gene ligated to heat-inducible hsp70i gene promoter demonstrated that OHBs did not induce cellular stress response. Finally, we demonstrate that doxorubicin conjugated with OHB is effectively taken up by murine melanoma B16(F10) cells in vitro and localizes in the cytoplasm. These data show for the first time that tailor-made biodegradable and biocompatible oligomers of 3-hydroxybutyric acid can be taken into consideration as effective, non-toxic vectors for delivery of drugs in a conjugated form.
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