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

Abstract

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 tertbutylcalix[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.

Curcumin and Fennel Essential Oil Improve Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome

“…Moreover, a pleiotropic effect for curcumin has been advocated and might involve antineoplastic and anticlastogenic properties by interacting with signal transduction and scavenging of free radicals at various levels in the body [35][36][37]. In this respect, the present and other formulations [38,39] containing curcumin might further improve its bioavailability and intracellular uptake ability.…”

Stimuli‐responsive liposomes for drug delivery

“…Significant enhancements in the release rate of hydrophilic (Ni 2+ ) and amphipathic (As 3+ ) anticancer agents were observed ( k (Ni 2+ , As 3+ ) = 8.25 h −1 , 14.7 h −1 , respectively) at pH 4.0, while profiles at pH 7.4 showed insignificant leakage ( k (Ni 2+ , As 3+ ) = <1 h −1 , 1.4 h −1 , respectively). Jelezova et al inserted poly(isoprene‐ b ‐acrylic acid) (pI‐pAA) diblock copolymers into liposomes to confer pH‐dependent delivery of curcumin using polyoxyethylated tert‐butylcalix[4]arene (BEC‐X) . The polyisoprene block served as the membrane anchoring moiety of the membrane disrupting agent and BEC‐X forms nanosized spherical aggregates with high solubilization for curcumin inside the liposomes.…”

Evaluating the effect of chitosan layer on bioaccessibility and cellular uptake of curcumin nanoemulsions

“…However, for the multilayer nanoemulsions, the H d remained stable after 54 h of assay (H d = 190.4 ± 3.1 nm), while no sign of curcumin was present in the acceptor medium (0 μg mL −1 , below the detection limit of 0.01 μg mL −1 ). Curcumin is reported as having low solubility in aqueous systems, 11 ng mL −1 , which could explain the absence of curcumin release (Jelezova et al, 2015;Zhao et al, 2012). The fact that at pH 2 the loss of WPI only occurred in nanoemulsions suggests that the chitosan layer was able to protect the WPI-stabilized nanoemulsions, improving their stability at acidic pH.…”