This study aimed to prepare andrographolide (AP)-loaded glycyrrhizic acid (GA) micelles (AP-GA)-PMs to enhance the solubility and anti-tumor effect of andrographolide. Firstly, andrographolide (AP) was used as the model drug and glycyrrhizic acid (GA) as carriers to prepare (AP-GA)-PMs. Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size, encapsulation efficiency (EE) and loading capacity of micelles. Finally, the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the (AP-GA)-PMs prepared by optimal process. The results showed that the prepared micelles under the optimal process had a nanosize of (127.11±1.38) nm, zeta potential of (-24.01±0.55) mV, the entrapment efficiency rate of (92.01±4.02)% , the drug loading rate of (51.44±1.24)% and high storage stability at 4 °C in 30 d, with slow but highly stable release. Moreover, (AP-GA)-PMs with the IC₅₀ value of 19.25 mg·L⁻¹ had a more synergistic and better anti-tumor effect in comparison with AP (IC₅₀=122.40 mg·L⁻¹) on HepG2 cells (P<0.01). In conclusion, the (AP-GA)-PMs prepared with glycyrrhizic acid as a carrier had a small particle size, large drug loading capacity, and high stability, and could significantly improve the anti-tumor effects of AP.
Antineoplastic Agents ; pharmacology ; Diterpenes ; pharmacology ; Drug Carriers ; chemistry ; Glycyrrhizic Acid ; chemistry ; Micelles ; Particle Size ; Polymers

With polyethylene glycol vitamin E succinate (TPGS) as the carrier materials, and berberine hydrochloride ( BER) as model drug, we formed berberine hydrochloride (BER) -loaded TPGS nanomicells (BER-PMs) using filming-rehydration method to improve its solubility and in vitro anti-tumor effect. The transmission electron microscope (TEM) was used to observe the particle appearance; particle detector was used to detect the diameter and Zeta potential; and ultracentrifugation was utilized to determine the encapsulation efficiency (EE) and drug-loading (DD); dynamic dialysis method was used to study the in vitro release behavior of BER-PMs, and the anti-tumor activity against MCF-7 cells was determined by MTT method. Results showed that the average particle size of BER-PMs was (12.45 ± 1.46) nm; particle size was uniform and spherical; drug loading and encapsulation efficiency were (5.7 ± 0.22)% and (95.67 ± 5.35)%, respectively. Zeta potential was (-1.12 ± 0.23) mV; release rate within 24 h was 37.20% and 41.14% respectively in pH 7.4 and pH 6.5 phosphate buffer in vitro; compared with BER, BER-PMs can significantly inhibit MCF-7 cell proliferation (P < 0.05), promote cell apoptosis and improve the anti-tumor activity of BER in vitro. Therefore, the formed berberine hydrochloride micelle can more effectively promote the apoptosis of MCF-7 cell, and improve the drug's in vitro anti-tumor effect.
Antineoplastic Agents ; chemistry ; pharmacology ; Berberine ; chemistry ; pharmacology ; Cell Death ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; MCF-7 Cells ; Particle Size ; Polymers ; chemistry ; pharmacology ; Solubility

N-acetyl-L-cysteine (NAC) capped quantum dots (QDs) were synthesized by a hydrothermal method and coated with 2-amino-2-deoxy-D-glucose (DG), polyethylene glycol (PEG), and 9-D-arginine (9R). The optical properties, morphology and structure of 9R/DG-coated CdTe QDs were characterized by ultraviolet-visible spectrometry, fluorescence spectrum, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), liquid chromatography-mass spectrometer (LC-MS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transmission electron micrographs (TEM). Furthermore, the biocompatibility, tumor targeted ability and transmembrane action of 9R/DG-coated CdTe QDs were studied. Results indicated that 9R/DG-coated CdTe QDs was constructed successfully by ligand exchange. The 9R/DG-coated CdTe QDs with the size of 8-10 nm had good dispersity and the absorbance and fluorescence peaks of CdTe QDs after modification were red shifted from 480 nm to 510 nm and 627 nm to 659 nm, respectively. In addition, the CdTe QDs modified by PEG, DG and 9R displayed good biocompatibility, high targeted ability to the cancer cells with glucose transporter type 1 (GLUT1) receptor high expression and obvious transmembrane ability.
Acetylcysteine ; chemistry ; Cadmium Compounds ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Polymers ; chemistry ; Quantum Dots ; chemistry ; Spectrophotometry, Ultraviolet ; Tellurium ; pharmacology

OBJECTIVETo prepare cisPLLAtin-loaded polylactic acid/cnts, and to study the anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines(MGC803 and MNK45).

METHODS5-FU-PLLA-CNTs were prepared with ultrasound emulsification. The morphology of 5-FU-PLLA-CNTs was determined by scanning electron microscope(SEM), and its drug loading and drug release curve in vitro were detected by UV-Vis-NIR spectrophotometer. Cells were divided into experiment, positive control and negative control groups. CCK8 method was used to test the cytotoxic effect of 5-FU-PLLA-CNTs in different concentrations on MGC803 and MNK45 cell proliferation. Flow cytometry was employed to measure the apoptotic rate of MGC803 and MNK45 cells before and after the intervention of 5-FU-PLLA-CNTs.

RESULTSDeep layer film of 5-FU-PLLA-CNTs was successfully established, whose drug-load rate was(4.54±0.43)%, entrapment rate was(21.56±2.36)%. In vitro release test showed release rate within 24 h of 5-FU-PLLA-CNTs was 23.9% in a as lowly increasing manner, and accumulating release rate was 85.3% at day 31. CCk8 experiment revealed, as compared to control group, 5-FU-PLLA-CNTs significantly inhibited the proliferation of two cell lines in dose-dependent and time-dependent manner. The best 5-FU-PLLA-CNTs concentration of inhibition for human gastric cancer cell lines was 1 mg/well. Flow cytometry indicated the apoptotic rate of MGC803 and MNK45 cells in experiment group treated by 1 mg/well 5-FU-PLLA-CNTs significantly increased as compared to negative control group (P<0.05), while the difference was not significant as compared to positive control group (P>0.05).

CONCLUSIONThe 5-FU-PLLA-CNTs has good drug sustained-release capacity, and can significantly kill and inhibit the proliferation of MGC803 and MNK45 cell lines.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Delayed-Action Preparations ; Fluorouracil ; pharmacology ; Humans ; Lactic Acid ; pharmacology ; Nanotubes, Carbon ; Polyesters ; Polymers ; pharmacology ; Stomach Neoplasms ; pathology

In this study, we prepared PLLA/bpV(pic) microspheres, a bpV(pic) controlled release system and examined their ability to protect nerve cells and promote axonal growth. PLLA microspheres were prepared by employing the o/w single emulsification-evaporation technique. Neural stem cells and dorsal root ganglia were divided into 3 groups in terms of the treatment they received: a routine medium group (cultured in DMEM), a PLLA microsphere group (DMEM containing PLLA microspheres alone) and a PLLA/bpV(pic) group [DMEM containing PLLA/bpV(pic) microspheres]. The effects of PLLA/bpV(pic) microspheres were evaluated by the live-dead test and measurement of axonal length. Our results showed that PLLA/bpV(pic) granulation rate was (88.2±5.6)%; particle size was (16.8±3.1)%, drug loading was (4.05±0.3)%; encapsulation efficiency was (48.5±1.8)%. The release time lasted for 30 days. In PLLA/bpV(pic) microsphere group, the cell survival rate was (95.2 ±4.77)%, and the length of dorsal root ganglion (DRG) was 718±95 μm, which were all significantly greater than those in ordinary routine medium group and PLLA microsphere group. This preliminary test results showed the PLLA/bpV(pic) microspheres were successfully prepared and they could promote the survival and growth of neural cells in DRG.
Animals ; Axons ; drug effects ; physiology ; Cells, Cultured ; Delayed-Action Preparations ; chemistry ; pharmacokinetics ; pharmacology ; Drug Compounding ; Female ; Ganglia, Spinal ; drug effects ; metabolism ; physiology ; Immunohistochemistry ; Lactic Acid ; chemistry ; pharmacokinetics ; pharmacology ; Microscopy, Electron ; Microspheres ; Neural Stem Cells ; drug effects ; physiology ; Neurofilament Proteins ; metabolism ; Neurons ; drug effects ; metabolism ; Organometallic Compounds ; chemistry ; pharmacokinetics ; pharmacology ; Polyesters ; Polymers ; chemistry ; pharmacokinetics ; pharmacology ; Pregnancy ; Rats

OBJECTIVETo overcome the deficiency in the current therapies for erectile dysfunction (ED), we designed and synthesized a novel high-efficiency polymer/gene compound drug controlled release system and discussed the feasibility of pH and temperature dually sensitive injectable hydrogel in ED gene therapy.

METHODSWe synthesized optimal siRNA gene nanoparticles by characterizing the zeta potential of polylysine (PLL)/siRNA gene compounds, and established a pH and temperature dually sensitive injectable gene compound drug controlled release system via Schiffs reaction between glycol chitosan (GC) and benzaldehyde capped OHC-PEO-PPO-PEO-CHO. Then we demonstrated the sustained release of the system at different temperatures.

RESULTSWhen the mass ratio of PLL to siRNA was 20:1, the zeta potential of the PLL/siRNA gene compound reached the peak (+23.5 mV) and the siRNA was encapsulated by PLL in the maximal degree. GC and OHC-PEO-PPO-PEO-CHO was crosslinked via benzoicimine reaction when environmental pH was changed from 5.5 to 7.4. The reslease of the siRNA encapsulated in this system kept at a low rate at 37 degrees C, significantly enhanced with the increase of the temperature to 60 degrees C, rising to (122.5 +/- 5.3) microg at 1 000 minutes as compared with (23.8 +/- 6.0) microg at 37 degrees C (P < 0.05).

CONCLUSIONThe polymer/gene compound drug controlled release system was successfully synthesized, which improved the stability and capacity of gene carriers and achieved siRNA release at different temperatures, promising to be a new approach to the gene therapy of ED.

Delayed-Action Preparations ; pharmacology ; Drug Delivery Systems ; Erectile Dysfunction ; drug therapy ; Genetic Therapy ; Humans ; Male ; Nanoparticles ; chemistry ; Polylysine ; chemistry ; Polymers ; RNA, Small Interfering ; pharmacology

To study the angiogenic activity of amphoteric brush-type copolymer complex of alginate-graft-PEI/pVEGF (Alg-g-PEI/pVEGF) in vivo, we evaluated the toxicity of Alg-g-PEI/pVEGF complexes to rMSCs and zebra fish first. Then, we used gel retardation assay to investigate the protection of complex to pDNA against DNase I, serum and heparin. For in vivo study, we evaluated the angiogenic activity of Alg-g-PEI/pVEGF complexes by using CAM and zebra fish as animal models, PEI 25K/pVEGF and saline as positive and negative controls. Our results show that Alg-g-PEI protected pVEGF from enzymolysis and displacement of heparin in some degree, and its complexes with pVEGF were less toxic to rMSCs and zebra fish. Alg-g-PEI/pVEGF complexes induced significant angiogenesis, which was dosage-dependent. In CAM, when the dosage of pVEGF was 2.4 microg/CAM, Alg-g-PEI group achieved the maximum of angiogenesis, and the area ratio of vessel to the total surface was 44.04%, which is higher than PEI 25K group (35.90%) and saline group (24.03%) (**P < 0.01). In zebra fish, the angiogenesis increased with the increase of N/P ratios of Alg-g-PEI/pVEGF complexes in our studied range; when N/P ratio was 110, the optimal angiogenesis was obtained with vessel length of 1.11 mm and area of 1.70 x 10(3) pixels, which is higher than saline group (0.69 mm and 0.94 x 10(3) pixels) (**P < 0.01) and PEI 25k group (0.82 mm and 1.11 x 10(3) pixels) (**P < 0.01). Our results demonstratethat Alg-g-PEI/pVEGF significantly induces angiogenesis in CAM and zebra fish, and has a great potential in therapeutic angiogenesis.
Alginates ; chemistry ; Angiogenesis Inducing Agents ; pharmacology ; Animals ; Chick Embryo ; Drug Carriers ; chemistry ; Genetic Vectors ; genetics ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Polyethyleneimine ; chemistry ; Polymers ; pharmacology ; toxicity ; Vascular Endothelial Growth Factor A ; chemistry ; Zebrafish

As a novel targeting drug delivery system, acid-sensitive micelles have many advantages, such as increasing solubility of lipophilic drugs, acid-sensitive release, high drug loading, etc. They can load drugs though non-covalent encapsulation and covalent conjugation methods. In tumor tissues, drugs are released quickly from the depolymerized micelles with lipophilic copolymer protonation or lypohydrophilic copolymer hydrolysis and covalent conjugated drugs are released when the acid-sensitive covalent linkage breaks. This review mainly advances acid-sensitive micelles for the tumor targeting drug delivery systems from drug-loaded methods and release mechanisms.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Humans ; Hydrogen-Ion Concentration ; Lactates ; chemistry ; Micelles ; Paclitaxel ; administration & dosage ; pharmacology ; Polyethylene Glycols ; chemistry ; Polymers

OBJECTIVETo develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro.

METHODSTriptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining.

RESULTSTriptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining.

CONCLUSIONTriptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cyclodextrins ; Diterpenes ; administration & dosage ; pharmacology ; Drug Carriers ; Epoxy Compounds ; administration & dosage ; pharmacology ; Humans ; Nanoparticles ; Phenanthrenes ; administration & dosage ; pharmacology ; Polyethyleneimine ; Polymers

The main objective of this study was to observe the adhesion, proliferation and differentiation of mouse osteblast-like MC3T3-E1 cells cultured on maleic anhydride-modified poly(D,L-lactic acid) (MPLA) and poly(D,L-lactic acid) (PDLLA) polymers, and to evaluate the cytocompatibility of MPLA polymer. The effects of MPLA and PDLLA polymers on the morphology, adhesion, proliferation, the content of total cellular protein, alkaline phosphatase (ALP) activity and the content of Ca of MC3T3-E1 cells were explored. These results indicated that MC3T3-E1 cells on MPLA polymer adhered and spread more fully. On MPLA polymer, the proliferation, total protein content, ALP activity, Ca content of the cells were significantly higher than those of the cells on PDLLA polymer (P < 0.01). It was concluded that MPLA polymer could promote the adhesion, spreading, proliferation and the synthesis of protein of osteoblasts, and also induced the differentiation and mineralization of osteoblasts, suggesting that MPLA polymer might have the better cytocompatibility than PDLLA.
Animals ; Biocompatible Materials ; chemistry ; pharmacology ; Cell Adhesion ; drug effects ; Cell Differentiation ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Embryo, Mammalian ; Lactic Acid ; chemistry ; pharmacology ; Maleic Anhydrides ; chemistry ; pharmacology ; Mice ; Osteoblasts ; cytology ; Polyesters ; Polymers ; chemistry ; pharmacology