Inhibiting Multidrug Resistance with Transferrin-Targeted Polymersomes through Optimization of Ligand Density.

Transferrin-conjugated polymersomes, transferrin-biotin/avidin/biotin-Pluronic F127-poly(lactic acid) (Tf-F127-PLA), were successfully prepared through a biotin-avidin bridging technique to study their ability to inhibit multidrug resistance of cancer cells. Hydrophilic doxorubicin (DOX) was selected as the model drug to be loaded into Tf-F127-PLA polymersomes. DOX loaded in Tf-F127-PLA polymersomes was released fast initially, followed by a slow release.

Synergistic antitumor effect of folate-targeted Pluronic™ F-127/poly(lactic acid) polymersomes for codelivery of doxorubicin and paclitaxel.

Folate-targeted Pluronic™ F-127/poly(lactic acid) (FA-F127-PLA) polymersomes were used as codelivery carriers of doxorubicin hydrochloride (DOX) and paclitaxel (PTX) to achieve a targeted synergistic antitumor effect. The cytotoxicity of PTX/DOX polymersomes against OVCAR-3 cells was determined by methyl thiazolyl tetrazolium assay. The cellular uptake of PTX/DOX polymersomes was examined by HPLC and micro-bicinchoninic acid techniques.

Co-Delivery of paclitaxel and doxorubicin in folate-Targeted pluronic/ploy (D,L-lactide--glycolide) polymersomes.

Drugs with different solubility can be selectively embedded into polymersomes with the hydrophilic core and hydrophobic bilayer. Novel folate-targeted Pluronic/poly (D,L-lactide--glycolide) polymersomes were constructed and used for the co-delivery of paclitaxel (PTX) and doxorubicin (DOX) to improve their inhibitory effect over cancer cells. The particle size of blank polymersomes was mainly distributed below 125 nm.

Transferrin/folate dual-targeting Pluronic F127/poly(lactic acid) polymersomes for effective anticancer drug delivery.

A novel dual-targeting Pluronic/poly(lactic acid) polymersome containing transferrin and folic acid ligands (Tf/FA-F127-PLA) has been designed to study its application in the targeted drug delivery system. Both biotin and folic acid conjugated Biotin/FA-F127-PLA polymersomes (Ps) were prepared as the precursor. The dual-targeting behaviors of Tf/FA-F127-PLA over C6 glioma cells were then fulfilled through connecting the precursor with biotinylated transferrin by using a three-step biotin-avidin technique.

Study on the Influencing Factors of Hypoglycemic Effect of Folate Targeted Polymersomes Encapsulating Insulin.

Purpose: To study the effects of the density of folic acid (FA) on the hypoglycemic ability of FA-targeted polymersomes as oral insulin carriers. Also to study the change of the hypoglycemic effect of FA-targeted mixed polymersomes added with various mass ratio of d-α-tocopherol polyethylene glycol 1000 succinate (TPGS).

Methods: The FA-targeted polymersomes with different FA molar contents were prepared.

Pharmacokinetics, mass balance, and metabolism of [C]vicagrel, a novel irreversible P2Y inhibitor in humans.

Vicagrel, a novel irreversible P2Y receptor inhibitor, is undergoing phase III trials for the treatment of acute coronary syndromes in China. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of vicagrel in six healthy male Chinese subjects after a single oral dose of 20 mg [C]vicagrel (120 µCi). Vicagrel absorption was fast (T = 0.

Folate-conjugated pluronic/polylactic acid polymersomes for oral delivery of paclitaxel.

Cancer chemotherapy and the patient's life will be more convenient if oral administration of anti-cancer drugs can be achieved. The feasibility of folate-targeted Pluronic F127/polylactic acid (FA-F127-PLA) polymersomes as the oral delivery carriers of paclitaxel (PTX) has been explored in this study. PTX loaded in FA-F127-PLA and PLA-F127-PLA polymersomes showed biphasic release behaviors in simulated gastric and intestinal fluids.

Effect of the Folate Ligand Density on the Targeting Property of Folated-Conjugated Polymeric Nanoparticles.

Targeted drug delivery systems have attracted increasing attention due to their ability for delivering anticancer drugs selectively to tumor cells. Folic acid (FA)-conjugated targeted block copolymers, FA-Pluronic-polycaprolactone (FA-Pluronic-PCL) are synthesized in this study. The anticancer drug paclitaxel (PTX) is loaded in FA-Pluronic-PCL nanoparticles by nanoprecipitation method.

The targeting properties of folate-conjugated Pluronic F127/poly (lactic-co-glycolic) nanoparticles.

Novel Folated Pluronic F127/poly (lactic-co-glycolic) (FA-F127-PLGA) and PLGA-F127-PLGA block copolymer were synthesized and nanoparticles self-assembled from these two copolymers were prepared by dialysis method. Paclitaxel (PTX) was successfully encapsulated in these two nanoparticles. According to in vitro release studies of PTX-loaded nanoparticles, after an initial burst release during the first 11h, the entrapped PTX released slowly in the following 82h.

Enhanced effect of folated pluronic F87-PLA/TPGS mixed micelles on targeted delivery of paclitaxel.

Targeted drug delivery systems have great potential to overcome the side effect and improve the bioavailability of conventional anticancer drugs. In order to further improve the antitumor efficacy of paclitaxel (PTX) loaded in folated Pluronic F87/poly(lactic acid) (FA-F87-PLA) micelles, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) were added into FA-F87-PLA to form FA-F87-PLA/TPGS mixed micelles. The LE of PTX-loaded mixed micelles (13.

Silencing of osterix expression by siRNA inhibits aldosterone‑induced calcification of vascular smooth muscle cells in mice.

The process of vascular calcification shares numerous similarities with that of skeletal mineralization and involves the deposition of hydroxyapatite crystals in arteries and cardiac valves. However, the underlying cellular mechanism remains to be fully elucidated. Microarray analysis in the present study demonstrated that greater than 2,000 genes were upregulated during the calcification of murine vascular smooth muscle cells (VSMCs), of which osterix (OSX) and integrin‑binding sialoprotein (IBSP) were the most significantly differentially expressed genes.

A review of biodegradable polymeric systems for oral insulin delivery.

Currently, repeated routine subcutaneous injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, patients' poor compliance for injections often fails to achieve the stable concentration of blood glucose. As a protein drug, the oral bioavailability of insulin is low due to many physiological reasons.

Pluronic P85/poly(lactic acid) vesicles as novel carrier for oral insulin delivery.

Poly(lactic acid)-b-Pluronic-b-poly(lactic acid) (PLA-P85-PLA) vesicles were developed as novel carrier for oral insulin delivery. PLA-P85-PLA block copolymer was synthesized by ring opening polymerization of the monomer l-lactide using Pluronic copolymer P85 as the initiator. Insulin-loaded PLA-P85-PLA vesicles were prepared by dialysis method and the mean diameter of insulin-loaded PLA-P85-PLA vesicles was determined to be 178 nm.

In vitro &in vivo targeting behaviors of biotinylated Pluronic F127/poly(lactic acid) nanoparticles through biotin-avidin interaction.

Biotinylated Pluronic F127/poly(lactic acid) block copolymers (B-F127-PLA) were successfully synthesized previously by our group. In the present study, the release behaviors of paclitaxel-loaded B-F127-PLA nanoparticles and their targeting properties to human ovarian carcinoma cells were investigated. Paclitaxel (pac) loaded in B-F127-PLA nanoparticles shows an initial burst release in the first 6h and followed by a slow release.

Active targeting behaviors of biotinylated pluronic/poly(lactic acid) nanoparticles in vitro through three-step biotin-avidin interaction.

In order to prepare targeted drug carriers, previously a biotin group has been attached by our group to the end of Pluronic F87/poly(lactic acid) and Pluronic P85/poly(lactic acid) block co-polymers to obtain B-F87-PLA and B-P85-PLA, respectively. In this paper, the active targeting properties of B-F87-PLA and B-P85-PLA nanoparticles in vitro were investigated through a three-step biotin-avidin interaction by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM). Two kinds of human ovarian cancer cells (OVCAR-3 and SKOV-3) and paclitaxel were chosen for the cytotoxicity tests.

[Incidence of metabolic disorders in patients with essential hypertension and patients with primary aldosteronism].

Objective: To compare the incidence of metabolic disorders (MS) in patients with primary aldosteronism (PA) and essential hypertension (EH).

Methods: MS prevalence was observed in 200 EH patients (male 104) and 220 PA patients (male 117) hospitalized to our hospital from August 2005 to March 2007.

Results: (1) The prevalence of MS in PA group was significantly higher than that of EH group (47.

[Aldosterone-to-renin ratio threshold for screening primary aldosteronism in Chinese hypertensive patients].

Objective: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become a most effectively and commonly used method for screening primary aldosteronism from hypertensive patients. It is known that there is a large variance in ARR value between races and ARR is affected by many factors, such as drugs, posture and serum potassium etc. The objective of this study is to establish the threshold of ARR for screening primary aldosteronism in Chinese hypertensive patients.

[A clinical intervention study among 463 essential hypertensive patients with metabolic syndrome].

Objective: To study the role of baseline risk factors in predicting the onset of diabetes among essential hypertensive patients with metabolic syndrome (MS) and to evaluate an ideal therapeutic regime that could reduce the risk factors and risk of onset of diabetes.

Methods: A randomized parallel clinical trial in essential hypertensive patients of grade 1 or 2 was conducted. Two of the three components (1) increased waist circumference and/or BMI; (2) increased triglycerides (TG) and/or decreased high-density lipoprotein cholesterol; (3) impaired glucose tolerance (IGT) were present define the MS.