Oligo-3-hydroxybutyrates as potential carriers for drug delivery.
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 microg/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.
Piddubnyak
Valeria
V
Department of Tumor Biology, Maria Skl?odowska-Curie Memorial Institute, Centre of Oncology, Branch Gliwice, Armii Krajowej 15, Gliwice 44-101, Poland.
Kurcok
Piotr
P
Matuszowicz
Andrzej
A
Głowala
Magdalena
M
Fiszer-Kierzkowska
Anna
A
Jedliński
Zbigniew
Z
Juzwa
Maria
M
Krawczyk
Zdzisław
Z
D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials; D015153:Blotting, Western; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental; D051379:Mice; D008956:Models, Chemical; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry; D011401:Promoter Regions, Genetic; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013696:Temperature; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D001672:Biocompatible Materials; D004396:Coloring Agents; D004337:Drug Carriers; D018840:HSP70 Heat-Shock Proteins; D011108:Polymers; D013778:Tetrazolium Salts; D013844:Thiazoles; D004317:Doxorubicin; D015500:Chloramphenicol O-Acetyltransferase; C022616:thiazolyl blue; D020155:3-Hydroxybutyric Acid