An in vitro study of liposomal curcumin: stability, toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B-cells.
Curcumin is a multi-functional and pharmacologically safe natural agent. Used as a food additive for centuries, it also has anti-inflammatory, anti-virus and anti-tumor properties. We previously found that it is a potent inhibitor of cyclosporin A (CsA)-resistant T-cell co-stimulation pathway. It inhibits mitogen-stimulated lymphocyte proliferation, NFkappaB activation and IL-2 signaling. In spite of its safety and efficacy, the in vivo bioavailability of curcumin is poor, and this may be a major obstacle to its utility as a therapeutic agent. Liposomes are known to be excellent carriers for drug delivery. In this in vitro study, we report the effects of different liposome formulations on curcumin stability in phosphate buffered saline (PBS), human blood, plasma and culture medium RPMI-1640+10% FBS (pH 7.4, 37 degrees C). Liposomal curcumin had higher stability than free curcumin in PBS. Liposomal and free curcumin had similar stability in human blood, plasma and RPMI-1640+10% FBS. We looked at the toxicity of non-drug-containing liposomes on (3)H-thymidine incorporation by concanavalin A (Con A)-stimulated human lymphocytes, splenocytes and Epstein-Barr virus (EBV)-transformed human B-cell lymphoblastoid cell line (LCL). We found that dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) were toxic to the tested cells. However, addition of cholesterol to the lipids at DMPC:DMPG:cholesterol=7:1:8 (molar ratio) almost completely eliminated the lipid toxicity to these cells. Liposomal curcumin had similar or even stronger inhibitory effects on Con A-stimulated human lymphocyte, splenocyte and LCL proliferation. We conclude that liposomal curcumin may be useful for intravenous administration to improve the bioavailability and efficacy, facilitating in vivo studies that could ultimately lead to clinical application of curcumin.
Department of Surgery, University of Kentucky, College of Medicine, Lexington, KY 40536, USA.
Changguo
C
Chen
Thomas D
TD
Johnston
Hoonbae
H
Jeon
Roberto
R
Gedaly
Patrick P
PP
McHugh
Thomas G
TG
Burke
Dinesh
D
Ranjan
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000633:toxicity; D004355:Drug Stability; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008081:Liposomes; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000633:toxicity; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018675:Toxicity Tests
D000970:Antineoplastic Agents; D008081:Liposomes; D010715:Phosphatidylglycerols; D002784:Cholesterol; C002773:dimyristoylphosphatidylglycerol; D003474:Curcumin; D004134:Dimyristoylphosphatidylcholine