ABSTRACT
OBJECTIVES: We aimed to develop lipid-polyethylene glycol (PEG)-polymer hybrid nanoparticles, which have high affinity to tumour tissue with active ingredient, a new generation antineoplastic drug, farnesylthiosalicylic acid (FTA) for treatment of glioblastoma. METHOD: Farnesylthiosalicylic acid-loaded poly(lactic-co-glycolic acid)-1,2 distearoyl-glycerol-3-phospho-ethanolamine-N [methoxy (PEG)-2000] ammonium salt (PLGA-DSPE-PEG) with or without 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) hybrid nanoparticles has been prepared and evaluated for in-vitro characterization. Cytotoxicity of FTA-loaded nanoparticles along with its efficacy on rat glioma-2 (RG2) cells was also evaluated both in vitro (in comparison with non-malignant cell line, L929) and in vivo. KEY FINDINGS: Scanning electron microscopy studies showed that all formulations prepared had smooth surface and spherical in shape. FTA and FTA-loaded nanoparticles have cytotoxic activity against RG2 glioma cell lines in cell culture studies, which further increases with addition of DOTAP. Magnetic resonance imaging and histopathologic evaluation on RG2 tumour cells in rat glioma model (49 female Wistar rats, 250-300 g) comparing intravenous and intratumoral injections of the drug have been performed and FTA-loaded nanoparticles reduced tumour size significantly in in-vivo studies, with higher efficiency of intratumoral administration than intravenous route. CONCLUSION: Farnesylthiosalicylic acid-loaded PLGA-DSPE-PEG-DOTAP hybrid nanoparticles are proven to be effective against glioblastoma in both in-vitro and in-vivo experiments.
Subject(s)
Brain Neoplasms/drug therapy , Farnesol/analogs & derivatives , Glioblastoma/drug therapy , Nanoparticles/administration & dosage , Polyethylene Glycols/administration & dosage , Polymers/administration & dosage , Salicylates/administration & dosage , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Brain Neoplasms/diagnostic imaging , Farnesol/administration & dosage , Farnesol/chemistry , Female , Glioblastoma/diagnostic imaging , Lipids/administration & dosage , Lipids/chemistry , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Polymers/chemistry , Rats , Rats, Wistar , Salicylates/chemistry , Treatment Outcome , Tumor BurdenABSTRACT
A high ruminal protein degradation is especially undesirable in high producing dairy cows and beef cattle, since these animals have high requirements of protein and the amount of protein that is not degraded by ruminal microorganisms and therefore enters the small intestine (so-called UDP = undegraded protein) is crucial. In this study, Merino rams with ruminal fistulas were used (n = 4) to determine the effect of glucose treatment of soybean meal (SBM), full fat soybean (FFSB) and soybean seed (SBS) on the ruminal degradability of dry matter (DM) and crude protein (CP). All these feedstuffs were grinded, diluted with water and heated (2 h; 100 degrees C) either without or with supplementation of 2 or 3% glucose (20 or 30 g glucose per kg dry feed). For the determination of the ruminal degradability nylon bag technique was used (incubation times: 2-48 h). In general ruminal degradability of protein in all three soy products was reduced by glucose treatment. In FFSB CP disappearance started to decrease after 8 h of incubation, whereas in SBM (+ 3% glucose) and SBS (+ 2 or 3% glucose) reduction of CP disappearance were time-independent. Further, effective degradability (Pe) of DM and CP of all feedstuffs were significantly reduced by glucose treatment, with the reduction being more pronounced when the glucose level was increased. When adding 3% of glucose, the Pe for CP was reduced by 6 (FFSB), 16 (SBM) and 18% (SBS), respectively. Explanation for the observed effects of a glucose supplementation (incl. water and heat treatment) is the reductive activity of glucose within these conditions.