Showing papers by "Jin-Wen Song published in 2016"

Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity.

Abstract: AR-23 is a melittin-related peptide with 23 residues Like melittin, its high α-helical amphipathic structure results in strong bactericidal activity and cytotoxicity In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23 Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents

Thermo-Sensitive Liposome co-Loaded of Vincristine and Doxorubicin Based on Their Similar Physicochemical Properties had Synergism on Tumor Treatment

Abstract: To develop vincristine (VCR) and doxorubicin (DOX) co-encapsulated thermo-sensitive liposomes (VD-TSL) against drug resistance, with increased tumor inhibition rate and decreased system toxicity, improving drug targeting efficiency upon mild hyperthermia (HT) in solid tumor. Based on similar physicochemical properties, VCR and DOX were co-loaded in TSL with pH gradient active loading method and characterized. The time-dependent drug release profiles at 37 and 42°C were assessed by HPLC. Then we analysed the phospholipids in filtrate after ultrafiltration and studied VD-TSL stability in mimic in vivo conditions and long-time storage conditions (4°C and −20°C). Cytotoxic effect was studied on PANC and sw-620 using MTT. Intracellular drug delivery was studied by confocal microscopy on HT-1080. In vivo imaging of TSL pharmacokinetic and biodistribution was performed on MCF-7 tumor-bearing nude mice. And therapeutic efficacy on these xenograft models were followed under HT. VD-TSL had excellent particle distribution (about 90 nm), high entrapment efficiency (>95%), obvious thermo-sensitive property, and good stability. MTT proved VD-TSL had strongest cell lethality compared with other formulations. Confocal microscopy demonstrated specific accumulation of drugs in tumor cells. In vivo imaging proved the targeting efficiency of TSL under hyperthermia. Then therapeutic efficacy revealed synergism of VCR and DOX co-loaded in TSL, together with HT. VD-TSL could increase drug efficacy and decrease system toxicity, by making good use of synergism of VCR and DOX, as well as high targeting efficiency of TSL.