Galactosylated Chitosan Modified Magnetic Mesoporous Silica Nanoparticles Loaded with Nedaplatin for the Targeted Chemo-Photothermal Synergistic Therapy of Cancer

The use of chemotherapy combined with photothermal therapy (PTT) is getting a focus topic for cancer treatment. Duing this research, the double targeting drug delivery system of nedaplatin (NDP)–carboxyl-functionalized magnetic mesoporous silica (MMSN-COOH)–galactosylated chitosan (GC) nanoparticles (NPs) was constructed. Because MMSNs have special physical properties, it can target to the specific area. In addition, it’s able to convert absorbed near-infrared (NIR) light into heat energy for photothermal therapy (PTT). Furthermore, the thermal energy generated by MMSNs under NIR lasers can accelerate the release of drug from preparations. Moreover, GC modified MMSNs-COOH as a carrier can increase the drug uptake of cancer cells that highly express galectins in vitro, resulting in cancer cell apoptosis, and thus increasing the targeting of cancerous tissue in vivo. The experimental consequences in vitro and in vivo revealed that the NDP@MMSNCOOH-GC NPs combined with PTT could avoid systemic toxicity and improve biosecurity while having good anticancer effect.

Development of Asialoglycoprotein Receptor-Targeted Nanoparticles for Selective Delivery of Gemcitabine to Hepatocellular Carcinoma

Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein receptors expressed on hepatocytes. Nanoparticles were formulated (G1–G5) by an ionic gelation method and evaluated for various physicochemical characteristics. Targeting efficacy of formulation G4 was evaluated in rats. Physicochemical characteristics exhibited by nanoparticles were optimal for administering and targeting gemcitabine effectively to the liver. The biphasic release behavior observed with G4 can provide higher drug concentration and extend the pharmacotherapy in the liver target site. Rapid plasma clearance of gemcitabine (70% in 30 min) from G4 was noticed in rats with HCC as compared to pure drug (p < 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; p < 0.0001) demonstrated excellent liver targeting by G4, while mitigating systemic toxicity. Morphological, biochemical, and histopathological examination as well as blood levels of the tumor marker, alpha-fetoprotein, in rats confirmed the curative effect of G4. In conclusion, this study demonstrated site-specific delivery and enhanced in vivo anti-HCC efficacy of gemcitabine by G4, which could function as promising carrier in hepatoma.

PSVII-16 Galactosylated chitosan-oligosaccharides have anti-adhesive effect against enterotoxigenic Escherichia coli in piglets

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in piglets. In vitro, high molecular weight β-galactosylated chitosan-oligosaccharides (Gal-COS) had strong anti-adhesive activity against ETEC-expressing K88 fimbriae (ETEC K88) binding to porcine erythrocytes. This study assessed the effects of Gal-COS differing in structure on anti-adhesive properties against ETEC in a small intestinal segment perfusion (SISP) model in 8 piglets (BW 10 kg; 5-wk old). With 10 jejunal segments in each pig, 5 segments were infected with ETEC K88, and the other 5 segments were infused with saline (non-ETEC). Every 2 paired segments (ETEC or non-ETEC) from the same pig were treated for 8 h with 64 ml of 10 g L-1 of one of the following test products: 1) α-Gal-COS; 2) β-Gal-COS; 3) exopolysaccharides produced by Lactobacillus reuteri; and 4) raffinose in a double 4 × 4 Latin square with a saline control. Infection by ETEC K88 was verified by quantitative PCR. Net fluid loss was calculated as difference of fluid loss between ETEC segment and its paired non-ETEC segment. Data were analyzed using the mixed model with segment and test product as fixed effects, and pig as random effect. Number of eubacterial rRNA genes was 10-fold greater (P < 0.001) in ETEC segments than non-ETEC segments, indicating that ETEC K88 accounted for > 90% of bacterial gene counts. Test product did not affect (P > 0.10) the number of ETEC bacteria in the outflow fluid. Furthermore, net fluid loss caused by ETEC tended (P = 0.08) to be decreased by β-Gal-COS compared to all other treatments. In conclusion, the in vivo SISP model confirmed that Gal-COS had anti-diarrheal effects, indicating that β-Gal-COS is a potential feed additive to reduce the ETEC-induced diarrhea in piglets.