Multidrug resistance (MDR) of breast cancer cells still represents an unmet medical need in chemotherapy. To this end, the purpose of this study was to determine efficacy of paclitaxel loaded in sterically stabilized, biocompatible and biodegradable sterically stabilized mixed phospholipid nanomicelles (SSMM; size, ~15 nm) and actively targeted vasoactive intestinal peptide-grafted SSMM (SSMM-VIP) in circumventing P-gp-mediated paclitaxel resistance in BC19/3 cells, a human breast cancer cell line that expresses >10-fold higher P-gp than its parental sensitive cell line, MCF-7. We found that in drug sensitive MCF-7 cells, paclitaxel loaded in SSMM (P-SSMM) and SSMM-VIP (P-SSMM-VIP) significantly inhibited cell growth in dose-dependent fashion (p<0.05). Both formulations were ~7-fold more potent than paclitaxel dissolved in DMSO (P-DMSO). Efficacy of P-SSMM and P-SSMM-VIP was similar (p>0.5). By contrast, in drug resistant BC19/3 cells, P-SSMM-VIP was significantly more effective than either P-SSMM or P-DMSO (~2-and 5-fold, respectively; p<0.05). Collectively, these data indicate that actively targeted paclitaxel-loaded SSMM-VIP overcomes multiple drug resistance of BC19/3 cells. We suggest this formulation should be further developed to treat MDR breast cancer.

Genes are attractive candidates as therapeutic agents, and the development of safe and effective gene carriers is essential for the success of human gene therapy. To develop a gene delivery vector that shows low cytotoxicity and high efficiency, we synthesized poly-L-lysine-g-pluronic by conjugating poly-L-lysine (PLL) to pluronic, which is partially functionalized with para-nitrophenyl carbonate groups, and evaluated for its efficiency as a possible nonviral gene carrier candidate. Structural analysis of synthesized polymer was performed by using 1H-NMR. Gel retardation assay, zeta potential and size measurement confirmed that the new gene carrier made a compact complex with plasmid DNA. pCMV-beta-gal was used as a reporter gene, and the in vitro transfection efficiency was measured in HeLa cells by using the o-nitrophenyl-beta-D-galactopyranoside assay. The highest transfection efficiency among those tested was achieved at the 1:1 weight ratio of polymer:DNA, and a 3-fold increase in transfection efficiency was achieved by treatment of a lysosomotropic agent, chloroquine. Compared with unmodified PLL, PLL-g-pluronic showed about 2-fold increase in transfection efficiency with similar cytotoxicity specifically at the 1:1 weight ratio of polymer:DNA.

Arbutins (α- and β-arbutins) are glycosylated hydroquinones that are commercially used in the cosmetic industry. These compounds have an inhibitory function against tyrosinase, a critical enzyme for generating pigments, which leads to the prevention of melanin formation, resulting in a whitening effect on the skin. Although β-arbutin is found in various plants including bearberry, wheat, and pear, α-arbutin and other arbutin derivatives are synthesized by chemical and enzymatic methods. This article presents a mini-review of recent studies on the production of α-arbutin and other α- and β-arbutin derivatives via enzymatic bioconversion methods. In addition, the structures of α- and β-arbutin derivatives and their biological activities are discussed. The catalytic characteristics of various enzymes used in the biosynthesis of arbutin derivatives are also reviewed.

Human neuropeptide Y (NPY) is an important biologics that regulates multitude of physiological functions and could be amenable to therapeutic manipulations in certain disease states. However, rapid (minutes) enzymatic degradation and inactivation of NPY precludes its development as a drug. Accordingly, we determined whether self-association of NPY with biocompatible and biodegradable sterically stabilized phospholipid micelles (SSM) improves its stability and bioactivity. We found that in saline NPY spontaneously aggregates whereas in the presence of SSM it self-associates with the micelles as monomers. Three NPY molecules self-associate with one SSM at saturation. This process stabilizes the peptide in α-helix conformation, abrogates its degradation by dipeptidyl peptidase-4 and potentiates NPY-induced inhibition of cAMP elaboration in SK-N-MC cells. Collectively, these data indicate that self-association of NPY with SSM stabilizes and protects the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro. We propose further development of NPY in SSM as a novel, long-acting nanomedicine.

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