Dissertation > Excellent graduate degree dissertation topics show

Preparation of a Hepatic Targeting Galactosylated Chitosan Nanoparticle Loaded Lactosyl-norcantharidin.

Author: HuZuo
Tutor: ZhangXueNong
School: Suzhou University
Course: Pharmacy
Keywords: norcantharidin chitosan activity and passive targeting metabolism
CLC: TB383.1
Type: Master's thesis
Year: 2011
Downloads: 63
Quote: 0
Read: Download Dissertation

Abstract


Objective Asialoglycoproteins receptor （ASGP-R）, expressed plentifully on the surface of hepatoma cells, can recognize terminalβ-D-galactose or N-acetylgalactosamineresidues. A hepatic targeting nanopartical was prepared using GC and Lac-NCTD to obtain active liver-targeting in addition to passive liver-targeting. Metabolism in rat liver microsomes of Lac-NCTD, which had not been researched extensively as a new derivative of norcantharidin, was investigated initially .Methods （1）Lac-NCTD GC NPs was obtained by ionic cross-linkage process and orthogonal design was used to optimize the formulation and preparation procedure with the particle size, PDI , entrapment efficiency and drug-loaded amount. （2） FT-IR, X-ray diffraction, DSC, TEM, etc. were used to evaluate the characteristics of Lac-NCTD GC NPs ; in vitro drug release of nanoparticles investigated by dialysis membrane. （3） In vivo anti-tumor activity of Lac-NCTD GC-NPs was evaluated in mice bearing H22 hepatoblastoma tumor with neoplasm volume, inhibition rate on tumor weight and Pathology characteristic photose. （4） IC50 of Lac-NCTD to SMMC-7721 and HepG 2 was studied by MTT Assay in order to provide basisi of uptake dosage. （5） HPLC was used to research the uptake of Lac-NCTD and nanoparticles in SMMC 7721 and HepG 2. （6） The rat liver microsomes was prepared by differential centrifugation technique and the enzyme kinetics parameters were calculated by Lineweave-Brurk. （7） Experiments incubated with inhibitors including Ketoconazole（CYP3A）, Quinidine（CYP2D6）, Phenacetin（CYP1A2） and 4-methylpyridine（CYP2E1） were carried out to investigate which subfamily of cytochrome P450 play important roles in Lac-NCTD metabolism.Results （1） The optimal preparation condition was as follows: GC concentrations was 2.5 mg·mL-1, Lac-NCTD:TPP was 1:4（m/m） and the temperature was 30℃. The average particle size of the nanoparticles were （142.22±5.20）%, PDI was （0.121±0.049）, entrapment rate was （73.82±0.51）%, drug-loading rate was （13.40±0.08）%. （2） The nanoparticles appear uniform and round under TEM and drug release followed Higuchi equation. （3） Among the treatment groups, both Lac-NCTD and Lac-NCTD-GC NPs were more powerful against the tumours than NCTD, and Lac-NCTD-GC NPs were the most powerful of all [28]. It was indicated that the Lac-NCTD entrapped in galactosylated nanoparticles administered in vivo may be able to display active and passive liver-targeting characteristics. （4） The uptake of Lac-NCTD-CS NPs indicated that adsorptive endocytosis existed as a nonspecific interaction of the cytomembrane compared with that of Lac-NCTD. The cellular uptake of Lac-NCTD-GC NPs showed that receptor-mediated endocytosis was generated by ligand binding to galactose receptors on hepatocytes. （5） Lac-NCTD-GC NPs had lower Vmax , Km and CLint than Lac-NCTD, indicating that NPs could step down the motebolism of Lac-NCTD in rat liver microsomes. It was suggested NPs could improve bioavailability of Lac-NCTD due to delaying the accretion rate. （6） In presence of Ketconazole the metabolism was inhibited significantly while other inhibitors had no inhibitory action.Conclusions The Lac-NCTD GC NPs appear uniform and round under TEM and drug release followed Higuchi equation. Compared with Lac-NCTD-CS NPs and Lac-NCTD , Lac-NCTD-GC NPs displayed active liver-targeting characteristics in addition to passive liver-targeting, more satisfactory compatibility with hepatoma cells and significant antitumor effect in hepatoma-bearing mice. Lac-NCTD-GC NPs could improve bioavailability of Lac-NCTD due to delaying the accretion rate, and Lac-NCTD is likely to be metabolism by CYP3A of rat liver microsomes, but further studies also should be taken on metabolism.

Related Dissertations

  1. Studies on Chitosan and Its Derivatives Adsorption for Paralytic Shellfish Poisoning in Ostrea Rivularis Could,TS254.4
  2. Research of Glycosaminoglycan from Perna Virids Effect on Blood Lipid,R285.5
  3. Thermal Stability of Complexes of Chitosan Quaternary Ammonium Salt and Metal Ion,O634
  4. Protein phosphatase 2A Cα subunit knockout cardiac energy metabolism due to remodeling,Q78
  5. Effects of Different Reconciled Corn Oils on Antioxidative Stress, Lipid Metabolism Enzymes, and Abundance of Immune-related Genes of Broilers,S831.5
  6. Polyethylenimine Conjugated Stearic Acid-g-chitosan Oligosaccharide Micelles for Antitumor Gene Therapy,R450
  7. Stereoselective Metabolism of Tetrahydropalmatine and Its Effect on Hepatic Drug Metabolism Enzymes,R96
  8. Preparation and Characterization of the OCS/PLLA Composite Film for Biomedical Materials,R318.08
  9. Study on the Accumulation and Remove of Cadmium and Lead in Oysters,X174
  10. Effects of Enzymes on Metabolism of Polycyclic Aromatic Hydrocarbons in Plant,X173
  11. Study on the Synthesis and Adsorption Behaviour of Chitosan Derivative,TS254.9
  12. Preparation and Properties of Chitosan-based Thermosensitive Composite Hydrogel,R943
  13. Effects of Nitrogen Management Practices on Expression and Degradation of Bt-protein in Transgenic Cotton,S562
  14. Effects of Different Models of Cultivation Management on Nitrogen and Carbon Metabolism and Grain Yield in Winter Wheat,S512.1
  15. Analysis on the Difference of Flue-cured Tobacco Metabolism and Quality Between Puer and Yuxi Areas in Yunnan Province,S572
  16. Sugar Metabolism and Related Enzyme During the Furity Development of Qingzhhong Loquat Cultivar,S667.3
  17. Study on Effects of Exogenous Auxin on Fructose Metabolism in Tomato Fruits,S641.2
  18. Effect of Different Electrical Voltages Stunning on Meat Quality of Broilers Postmortem,S831
  19. The Preparation of Flurbiprofen-chitosan Hydrogel in Situ and Study on Intrawound Analgesia Effect Afterincisional Administration to Rats,R614
  20. Application of Glycol Chitosan-based Hydrogels in Tissue Engineering and Drug Delivery,R943
  21. Controlled Synthesis of Stimuli-Responsive Chitosan Derivatives in Drug Delivery,TQ460.1

CLC: > Industrial Technology > General industrial technology > Materials science and engineering > Special structural materials
© 2012 www.DissertationTopic.Net  Mobile