Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems

Jelezova, Ivelina and Drakalska, Elena and Momekova, Denitsa and Shalimova, Natalia and Momekov, Georgi and Konstantinov, Spiro and Rangelov, Stanislav and Pispas, Stergios (2015) Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems. European Journal of Pharmaceutical Sciences, 78. pp. 67-78.

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Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells.

Item Type: Article
Subjects: Medical and Health Sciences > Other medical sciences
Divisions: Faculty of Medical Science
Depositing User: Elena Drakalska
Date Deposited: 14 Aug 2015 10:35
Last Modified: 14 Aug 2015 10:35

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