Research progress of environment-responsive delivery system in the application of co-delivery gene and drug / 药学学报

With the development of polymeric materials and nanotechnology, the potential application of nanoscaled drug delivery system (NDDS) is gradually manifested in the field of pharmaceutics. Especially, NDDS has the obvious advantages in the delivery of gene or drug. Comparing to the delivery system of single-drug, co-delivery system of gene and drug can significantly improve the therapeutic effects by enhancing transfection efficiency of gene and reversing multidrug resistance, etc. The co-delivery systems of gene and drug, which had the triggered release characteristics in the inner and outer of tumor, could be constructed by introducing the environment-responsive (pH-responsive, redox-responsive and light-responsive, etc) groups into the co-delivery system. The antitumor activity was further improved. In the present paper, the environment- responsive delivery systems in the application of co-delivery gene and drug in recent years were reviewed, and their remarkable properties in the antitumor activity were analyzed and summarized.

Progress in the study of core-crosslinked polymeric micelles in drug delivery system / 药学学报

The core-crosslinked polymeric micelles were used as a new drug delivery system, which can decrease the premature drug release in blood circulation, improve the stability of the micelles, and effectively transport the drug into the therapy sites. Then the drug bioavailability increased further, while the side effect reduced. Most drugs were physically entrapped or chemically covalent with the polymer in the internals of micelles. Based on the various constitutions and properties of polymeric micelles as well as the special characteristics of body microenvironment, the environment-responsive or active targeting core-crosslinked micelles were designed and prepared. As a result, the drug controlled release behavior was obtained. In the present paper, the research progress of all kinds of core-crosslinked micelles which were published in recent years is introduced. Moreover, the characteristic and application prospect of these micelles in drug delivery system are analyzed and summarized.

Preparation and anti-tumor effect in vitro of doxorubicin-loaded targeting micelles modified by folic acid / 中国药学杂志

OBJECTIVE: To prepare doxorubicin (DOX)-loaded micelles based on folic acid-modified cholesterol-glycol chitosan (FCHGC), and study its physicochemical properties and cytotoxicity in vitro. METHODS: FCHGC copolymer was synthesized by conjugating carboxyl groups of folic acid with the primary amino groups of cholesterol-modified glycol chitosan (CHGC) in the presence of coupling agent. FCHGC conjugate was characterized by 1H-NMR and fluorescence measurement using pyrene as a probe. The DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The size and shape of the micelles were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). DOX release behavior was studied in vitro by a dialysis method in phosphate buffer saline (PBS, pH 7.4). The cytotoxicity and celluar uptake of drug-loaded micelles in vitro were investigated by 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. RESULTS: The critical aggregation concentration (CAC) of the FCHGC micelles in aqueous solution was 0.0163 mg·mL-1. Its particle size was 227 nm. The drug loading and encapsulation efficiency of DOX-loaded FCHGC (DFCHGC) micelles were 10.5% and 78.5%, respectively. The shape of DFCHGC micelles was almost spherical. DOX was released from DOX-loaded micelles in a biphasic manner, which displayed an initial rapid release phase and a later sustained release phase. The 50% inhibitory concentrations (IC50) of DOX, DOX-loaded CHGC (DCHGC) and DFCHGC micelles, incubated with folate receptor (FR)-negative A549 cells for 48 h, were 1.493, 0.620 and 0.974 μg·mL-1, respectively. Therefore, DCHGC micelles exhibited much more potent cytotoxicity against A549 cells than DFCHGC micelles. In FR-positive HeLa cells, the IC50 values of DOX, DCHGC and DFCHGC micelles were 1.398, 0.662 and 0.259 μg·mL-1, respectively. The DFCHGC micelles showed the greatest cytotoxicity among three DOX formulations for HeLa cells. And DFCHGC micelles exhibited greater cellular uptake than free DOX and DCHGC micelles in HeLa cells. CONCLUSION: The FCHGC micelles as a drug carrier for DOX delivery show selectively targeting to FR-positive cells, and improve the anti-tumor activity of DOX. These results suggested that FCHGC micelles could be a potential carrier for active targeting drug delivery.

Tissue distribution of doxorubicin-loaded nanoparticles based on cholesterol-modified glycol chitosan in S180-bearing mice / 中国药学杂志

OBJECTIVE: To study the tissue distribution of doxorubicin-loaded cholesterol-modified glycol chitosan nanoparticles (named as DCN-16) in S180-bearing mice. METHODS: After intravenous administration of doxorubicin (DOX) or DCN-16, DOX concentrations in plasma and tissues samples which were collected at predetermined time were determined by high performance liquid chromatography (HPLC). And DOX distribution and targeting performance in vivo were evaluated. RESULTS: DCN-16 displayed long circulation time in S180-bearing mice. The area under the curve (AUC0-∞) of DCN-16 was lower in heart (P < 0.05), lung (P < 0.05) and kidney (P < 0.05) than that of free DOX. In addition, compared with free DOX, DCN-16 also produced significantly increased drug accumulation in liver (P < 0.05), spleen (P < 0.05) and tumor (P < 0.05). The relative tissue exposure (Re) of DCN-16 in tumor was 2.56-folds of free DOX. CONCLUSION: Encapsulating DOX with cholesterol-modified glycol chitosan nanoparticles can prolong the systemic circulation time of DOX, increase its anti-tumor targeting activity and reduce its cardiac toxicity.