OBJECTIVE Chitosan(CS)is a natural cationic polysaccharide composed of N-acetylglucosamine and glucosamine *** has been widely used in preparing drug delivery systems because of its attractive non-toxicity,biocompatib...
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OBJECTIVE Chitosan(CS)is a natural cationic polysaccharide composed of N-acetylglucosamine and glucosamine *** has been widely used in preparing drug delivery systems because of its attractive non-toxicity,biocompatibility,biodegradability,mucoadhesion and the ability to transiently open the tight junctions of the intestinal barrier;β-cyclodextrin(β-CD)has a hydrophilic outer surface and a lipophilic central cavity which can accommodate a variety of lipophilic drugs due to hydrophobic *** is known to enhance the solubility of the incorporated drugs,to act as permeation enhancer for macromolecular drugs,to improve chemical and physical stability and to inhibit the activity of certain *** to the advantages of bothβ-CD and CS,the objective of this study was to develop novel nano-drug delivery systems(NDDS)made of CS andβ-CD for poorly water-soluble drugs:chitosan bearing pendant p-cyclodextrin(CD-g-CS)nanoparticles and N-maleoyl chitosan bearing pendantβ-cyclodextrin(CD-g-NMCS)nanoparticles,thus laying a solid foundation for their further development. METHODS ***-g-CS polymer was synthesized with CS and mono-6-deoxy-6-(p-toluene-sulfonyl)-β-cyclodextrin(6-OTs-β-CD),which was prepared withβ-CD and p-toluenesulfonyl *** different substitute degrees ofβ-CD on CD-g-CS(DSCD=9.6%, 14.0%and 20.0%)were obtained by controlling the mole ratio ofβ-CD to CS and confirmed by 1HNMR,IR,XRD;CD-g-NMCS polymer was synthesized by reacting maleic anhydride with CD-g-CS(DSCD=14.0%).Two different carboxyl substitute degrees (DSCOOH=21.2%and 30.5%)of CD-g-NMCS were obtained by adjusting mass ratio of maleic anhydride to CD-g-CS and also confirmed by 1HNMR,IR,*** final polymers were dialyzed against deionized water and *** water-solubility, viscosity average molecular weight and cell toxicity of the polymers were examined. ***-g-CS nanoparticles were prepared through an ionic gelation method using sodium tripolyphosphate(TPP)as cross
Dual-decorated liposomes with pH-selective cell penetrating peptides(CPPs)and active tumor targeting hyaluronic acid (HA)were fabricated for targeting anticancer drug delivery.A series of novel synthetic tumor pH-trig...
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Dual-decorated liposomes with pH-selective cell penetrating peptides(CPPs)and active tumor targeting hyaluronic acid (HA)were fabricated for targeting anticancer drug delivery.A series of novel synthetic tumor pH-triggered CPPs were screened by comparing tumor cellular uptake efficiency at pH 6.4 with at pH 7.4,and R6H4(RRRRRRHHHH)rich in arginines and histidines was obtained for the strongest *** construct R6H4-modified liposomes(R6H4-L),R6H4 with stearyl was anchored into liposomes due to hydrophobic *** was utilized to shield positive charge of R6H4-L to assemble HA coated R6H4-L (HA-R6H4-L)by electrostatic effect for improved plasma *** rapid degradation of HA by hyaluronidase(HAase)was demonstrated by the viscosity and zeta potential detection,allowing the R6H4 exposure of HA-R6H4-L at HAase-abundant tumor *** HAase treatment,paclitaxel-loaded HA-R6H4-L(PTX/HA-R6H4-L)presented a remarkably stronger cytotoxicity toward the hepatic cancer(HepG2)cells at pH 6.4 relative to pH 7.4,and additionally coumarin 6-loaded HA-R6H4-L (C6/HA-R6H4-L)showed efficient intracellular trafficking including endosomal/lysosomal escape and cytoplasmic liberation by confocal laser scanning microscopy(CLSM).In vivo imaging verified the reduced accumulation of near infrared dye 15 (NIRD15)-loaded HA-R6H4-L(NIRD/HA-R6H4-L)at the tumor site when mice were pretreated with an excess of free HA, indicating the active tumor targeting of ***,the antitumor efficacy of PTX/HA-R6H4-L was higher than that of PC-based liposomes against a xenograft hepatic cancer(Heps)tumor in *** findings demonstrate the feasibility of using tumor pH-sensitive CPPs and active targeting HA to extend the applications of liposomal nanocarriers to efficient anticancer drug delivery.
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