1.Future Direction of Nanomedicine in Gastrointestinal Cancer.
The Korean Journal of Gastroenterology 2007;49(5):271-279
Cancer is one of the leading causes of death in human, and among various cancers, gastrointestinal cancers occupy more than 55%. Gastric cancer is the first leading cause of cancer-related mortality in the world and the number of pancreas and colon cancers are increasing remarkably during last two decades which will continue to increase in the future. Even though the clinical importance of gastrointestinal cancers is very high and endless efforts has been made to develop novel diagnostic and therapeutic methods to improve the patient's quality of life and survival, the realistic advance in the actual survival benefit of the cancer patients are still strongly required. Nanotechnology has the power to radically change the way of cancer diagnosis and treatment. Currently, there is a lot of researches on novel nanodevices capable of detecting cancer at its earliest stage, pinpointing its location within the body, and delivering anticancer drugs specifically to the malignant cells. Nanoscale devices can readily interact with biomolecules both on the cell surface and within the cell. In addition, nanoscale devices are already proven that they can deliver therapeutic agents to target cells even within specific organelles. Major areas in which nanomedicine is being developed in cancer include early detection and proteomics, imaging diagnostics and multifunctional therapeutics. Because nanotechnology would provide a technical power and tool that enable new diagnostics, therapeutics, and preventives to keep pace with today's explosion in knowledge in the future, it would be very useful to know the perspectives in the direction of nanotechnology as a major clinician responsible for the patients with gastrointestinal malignancies.
Drug Delivery Systems
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Gastrointestinal Neoplasms/*diagnosis/*drug therapy
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Humans
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Nanocapsules/therapeutic use
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*Nanomedicine
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Nanoparticles/diagnostic use/therapeutic use
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Nanotechnology
2.Pharmacokinetics and bioequivalence assessment of a self-assembled asparaginase nanocapsule in rats.
Zijun YAN ; Jiangchuan XIE ; Dan HE ; Xueyuan HU ; Jingqing ZHANG
Journal of Southern Medical University 2016;36(1):90-93
OBJECTIVETo study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-β-cyclodextrin nanocapsules (AHSP) in SD rats.
METHODSThe morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase.
RESULTSAHSP had an average particle size of 413.80∓10.97 nm with a zeta potential of -20.37∓2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34∓1.82 U/mL and 46.38 ∓1.98 U/mL, and their AUC(0-∞) was 164.66∓6.88 U/mL and 51.44∓3.01 U/mL with half-lives of 4.62∓0.60 h and 1.86∓0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-∞), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-∞) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively.
CONCLUSIONAHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.
Animals ; Area Under Curve ; Asparaginase ; pharmacokinetics ; Biological Availability ; Half-Life ; Injections, Intravenous ; Nanocapsules ; Rats ; Rats, Sprague-Dawley ; Therapeutic Equivalency
3.Study on mass transfer behavior of hemoglobin-based nanocapsule surface.
Yan SHENG ; Yuan YUAN ; Xiaoqian SHAN ; Xiaolan ZHANG ; Xuying CAO
Journal of Biomedical Engineering 2008;25(4):879-884
Three dimensional structure of the surface is an important factor that influences the mass transfer behavior of hemoglobin-based nanocapsule surface. In this paper, the modified double emulsion method was used to fabricate the blood substitute of hemoglobin-based nanocapsules, and with the use of different molecular weight of PEG as probes, the effects of different technical conditions (such as primary emulsion, double emulsion, polymer, solvent, et al) in the processing on the three dimensional structure of the nanocapsule surface were investigated in details. Researches indicated that the water-soluable solvent, such as ethyl acetate and acetone could effectively modulate the pore size of the nanocapsule surface. With the increasing of the ratio of water-soluble solvent, the pore size of the nanocapsules firstly increased and then decreased. The increasing of the extra-water volume, the prolongation of the solvent evaporation time, and the improvement of the stirring speed resulted in a bigger pore size, but the increasing of the solvent volume and PEG polymer could reduce the pore size of nanocapsule surface.
Acetone
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chemistry
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Animals
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Biocompatible Materials
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chemistry
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Blood Substitutes
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chemical synthesis
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chemistry
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metabolism
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Cattle
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Emulsions
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Hemoglobins
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chemistry
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Nanocapsules
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chemistry
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Porosity
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Solvents
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Surface Properties
4.Prolonged-releasing performance of drug loaded polyelectrolyte nanocapsules effected by acid phosphatease: in vitro analysis.
Lei JIANG ; Suyun CHEN ; Xiaoling YANG ; Jing YI ; Peiyong LI
Chinese Journal of Biotechnology 2008;24(10):1801-1807
The aims of the study were to prepare polyelectrolyte nanocapsules effected by acid phosphatease (ACP) and to study prolonged-releasing performance of the nanocapsules in vitro. Using the layer by layer (LbL) self-assembly technique, polyelectrolyte-beta-glycerophosphoric acid nanocapsules were prepared. The morphologies of the nanocapsules were characterized by transmission electron microscopy (TEM) and biocompatibility was well examined by cell-culture method. The drug adriamycin would be loaded in nanocapsules for concentration gradient, the encapsulation efficiency could be calculated. Nanocapsules were reacted with acid phosphatease standard and HepG2 cells that express the ACP, respectively. The prolonged-releasing of adriamycin was verified and tumor cells apoptosis were measured. TEM images showed that the nanocapsule sizes were between 200-300 nm. The material biocompatibility was good until the concentration of nanacapsule was up to 250 microg/mL. The drug encapsulation efficiency reached 68.12%. The release rate of polyelectrolyte (PAH/PSS-beta-glycerophosphoric acid)s nanocapsules was higher than in the control nanocapsules at 48 h (38% Vs 15%) after its reaction to the ACP standard (P < 0.05). Compared with the control, nanocapsules could significantly inhibit the growth of HepG2 cells that expressed the ACP, and the efficiency of cell apoptosis was 7.59% higher at 24 h (13.73 Vs 6.14, P < 0.05). Polyelectrolytes (PAH/PSS-beta-glycerophosphoric acid) nanocapsules in vitro have response to acid phosphatease by which prolonged-releasing can be affected. This property can be used for treatment of some malignant and benign diseases with elevated acid phosphatease level.
Acid Phosphatase
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pharmacology
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Antibiotics, Antineoplastic
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administration & dosage
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Delayed-Action Preparations
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chemical synthesis
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Doxorubicin
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administration & dosage
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Electrolytes
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chemistry
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Hep G2 Cells
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Humans
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Nanocapsules
5.Experimental study of tissue-engineered skin loaded with keratinocyte growth factor nanocapsules for skin defect.
Bin YANG ; Ri-Sheng QIU ; Qing-Qi HONG ; Chen-Yang JI
Chinese Journal of Plastic Surgery 2009;25(3):200-204
OBJECTIVETo study the effect of tissue-engineered skin loaded with keratinocyte growth factor (KGF) nanocapsules for skin defect on athymic mice.
METHODSThe acellular dermal matrix (ADM) loaded with KGF-ADM was constructed by means of phacoemulsification solvent evaporation and low temperature drying. The human epidermal stem cells and fibroblasts were captured and identified, then cultivated on the surface of the KGF-ADM. The cell growth was observed. The tissue-engineered skin without KGF was used as sham group. The autogenous skin graft was used as control group. 2 and 6 weeks after the skin was transplanted to the back of athymic mice, the contraction and histological healing of the transplanted skins were observed respectively. Then the immunofluorescence examination with anti-human K10-FITC and beta1-integrin-Cy3 were applied to detect the origin, growth and differentiation of epidermal and dermal cells in tissue-engineered skin.
RESULTSThe epidermal stem cells grew well and attached tightly on KGF-ADM. There were small round stem cells and polygonal terminally-differentiated cells, which appeared a partly cloning growth and a tendency of merging. The tissue-engineered skin with KGF nanocapsules gained better result in repairing the skin defects as compared with the blank group and the control group 2 and 6 weeks after transplantation. The regenerative skin cells could connect and mix closely with the athymic mouse skin cells on the border of skin defect. Meanwhile, the regenerative skin existed some contraction. The histological observation with HE staining showed that the regenerative skin possessed intact epidermis with several cell layers and normal keratose stratum, among which there were still some beta1-integrin (+) cells which represented epidermal stem cells or transient amplifying cells when they were tested by immunofluorescence after 6 weeks of transplantation.
CONCLUSIONSThe tissue-engineered skin loaded with KGF nanocapsules had a better result in repairing athymic mice skin defects than common tissue-engineered skin without KGF nanocapsules or skin auto-graft.
Animals ; Cell Culture Techniques ; Cells, Cultured ; Dermatologic Surgical Procedures ; Dermis ; cytology ; Epidermis ; cytology ; Fibroblast Growth Factor 7 ; Fibroblasts ; cytology ; Humans ; Mice ; Mice, Nude ; Nanocapsules ; Skin ; cytology ; injuries ; Skin Transplantation ; Tissue Engineering ; methods ; Tissue Scaffolds
6.Delta12-prostaglandinJ2-nano capsule up-regulates growth factor expression and enhances bone regeneration in rats.
Lili CHEN ; Fen WEI ; Weilian SUN ; Peihui DING ; Xiaotao CHEN ; Yanmin WU ; Email: WYM731128@126.COM.
Chinese Journal of Stomatology 2015;50(3):151-156
OBJECTIVETo investigate the effect of local delivery of delta12-prostaglandinJ2-loaded poly (lactic-co-glycolic acid) (Δ(12)-PGJ2-NC) on growth factors expression and bone formation.
METHODSΔ(12)-PGJ2-NC was prepared by the emulsion solvent diffusion method. The physical and chemical properties of the nanoparticles were evaluated by particle size analysis, transmission electron microscopy, drug-loading ratio and the in vitro release study. Then standardized transcortical defect (5.0 mm × 1.5 mm) was conducted in the femur of 48 male Wistar rats which were randomly divided into four groups (n = 12), S, K, F, and N. Thirty microliter of saline (S), unloaded nanoparticles (K), Δ(12)-PGJ2 (F) and Δ(12)-PGJ2-NC(N) in a collagen vehicle were delivered inside a titanium chamber fixed over the defect. Then, four subgroups were randomly divided in each group named as D3, D7, D14, and D28 (n = 3) according to the days 3, 7, 14, and 28 after the surgery. At days 3, 7, 14, and 28, the mRNA expression of the bone morphogenetic protein-6 (BMP-6), platelet-derived growth factor-B (PDGF-B) in defect aera was analyzed by real time quantitive-polymerase blotting. HE staining was employed to reveal new bone formation in weeks 2 and 4.
RESULTSΔ(12)-PGJ2-NC appeared opalescent white and remained relatively stable, with an average particle size of (135.2 ± 0.85) nm. The images from transmission electron microscopy showed that Δ(12)-PGJ2-NC was spherical in shape and homogeneously distributed. The encapsulation efficiency of Δ(12)-PGJ2 with the poly (lactic-co-glycolic acid) (PLGA) nanocapsules was about 92%. The in vitro release of Δ(12)-PGJ2-NC at 37 °C showed a sustained fashion and the average accumulated amount was 30%, 52%, 77%, 91%, and 98% respectively, at 0.5, 1, 2, 4 and 6 h. Compared with the animals treated with saline, after dose of 100 mg/L Δ(12)-PGJ2 and Δ(12)-PGJ2-NC apllication, the mRNA expression level of BMP-6, PDGF-B increased significantly (P < 0.05, P < 0.001). The protein expression of BMP-6, Ephrin-B2 also was up-regulated. Histomorphometry revealed that new bone formation increased at the same dose of 100 mg/L. But the unloaded nanoparticles did not have the same effect (P > 0.05).
CONCLUSIONSA stable Δ(12)-PGJ2 loaded nanoparticle was successfully prepared. Δ(12)-PGJ2-NC may upregulate the expression of BMP-6, PDGF-B and Ephrin-B2, and promote new bone formation in bone defect area.
Animals ; Bone Morphogenetic Protein 6 ; genetics ; metabolism ; Bone Regeneration ; drug effects ; Ephrin-B2 ; genetics ; metabolism ; Femur ; drug effects ; surgery ; Lactic Acid ; pharmacokinetics ; pharmacology ; Male ; Nanocapsules ; administration & dosage ; Nanoparticles ; administration & dosage ; Particle Size ; Polyglycolic Acid ; pharmacokinetics ; pharmacology ; Prostaglandin D2 ; pharmacokinetics ; pharmacology ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, Platelet-Derived Growth Factor beta ; genetics ; metabolism ; Time Factors ; Up-Regulation