Intelligent polymeric micelles: development and application as drug delivery for docetaxel.

Recent years, docetaxel (DTX)-loaded intelligent polymeric micelles have been regarded as a promising vehicle for DTX for the reason that compared with conventional DTX-loaded micelles, DTX-loaded intelligent micelles not only preserve the basic functions of micelles such as DTX solubilization, enhanced accumulation in tumor tissue, and improved bioavailability and biocompatibility of DTX, but also possess other new properties, for instance, tumor-specific DTX delivery and series of responses to endogenous or exogenous stimulations. In this paper, basic theories and action mechanism of intelligent polymeric micelles are discussed in detail, especially the related theories of DTX-loaded stimuli-responsive micelles. The relevant examples of stimuli-responsive DTX-loaded micelles are also provided in this paper to sufficiently illustrate the advantages of relevant technology for the clinical application of anticancer drug, especially for the medical application of DTX.

Polymer-drug conjugates: present state of play and future perspectives.

Polymer conjugation is an efficient approach to improve therapeutic properties of drugs and biological agents. Since the first synthetic polymer-drug conjugate entered clinical trials in 1994, this technology has undergone notable development for the introduction and study of novel polymers and for the progress in the biological rationale for designing conjugates. Not surprisingly, new polymers, in addition to the best known polyethylene glycol, poly[N-(2-hydroxypropyl)methacrylamide], are continuously conjugated with drugs to achieve biodegradable, stimuli-sensitive and targeted systems in an attempt to prolong blood circulation times and enhance drug concentrations at the intended site of action. This overview focuses on bioconjugates of water-soluble polymers with low molecular weight drugs. Additionally, the most recent achievements in the polymer-drug conjugate field and several promising approaches for the future are discussed.

The permeability of puerarin loaded poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 on the blood-brain barrier and its protective effect against cerebral ischemia/reperfusion injury.

Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood-brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 nm and the zeta potential of -7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.

Reduced folate carrier A80G polymorphism and susceptibility to neural tube defects: a meta-analysis.

The reduced folate carrier (RFC1) plays a crucial role in mediating folate delivery into a variety of cells. RFC1 polymorphism (A80G) has been reported to be associated with increased risk of neural tube defects (NTDs). However, results derived from individually underpowered studies are conflicting. We performed a systematic search of MEDLINE and EMBASE databases and carried out a meta-analysis on the association between RFC1 polymorphism (A80G) and NTDs risk. Overall, a significant correlation between RFC1 A80G polymorphism and NTDs risk was found neither in infants nor in maternal (allele contrast in infants: OR(RE)=1.15, 95% CI: 0.92-1.45; allele contrast in mothers: OR(RE)=1.24, 95% CI: 0.98-1.56). The present meta-analysis failed to support a positive association between RFC1 A80G polymorphism and susceptibility to NTDs. It is important to realize, however, that socio-economic factors, and gene-environment and gene-gene interactions, could have influenced the outcome of our meta-analysis. For this reason, a relationship between the A80G polymorphism and NTD risk cannot be entirely discounted.

[Preparation and physiochemical properties of curcumin-loaded lipid cubic liquid crystalline nanoparticles].

OBJECTIVE: To prepare curcumin-loaded lipid cubic liquid crystalline nanoparticles and evaluate its physiochemical properties. METHODS: The nanoparticles were prepared using hot and high-pressure homogenization. The prescription and preparation process were optimized by uniform design with drug loading and entrapment efficiency as indexes. RESULTS: The nanoparticles were spherical under transmission electron microscope (TEM) with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 +/- 0.2)% and entrapment efficiency of (95 +/- 1.8)%. The release equation: In (1-Q) = -0.0251t-0.0075. The cumulative release percentage was 60% at 36 h in vitro. CONCLUSION: The obtained curcumin-loaded lipid cubic liquid crystalline nanoparticles shows high entrapment efficiency and good sustain release property.

[Preparation and in vitro characterization of apigemin-loaded nanostructured lipid carriers].

OBJECTIVE: To prepare Apigemin-loaded nanostructured lipid carriers (Api-NLCs) and evaluate their characteristics. METHODS: Api-NLCs were prepared by the method of emulsion evaporation-solidification at low temperature. The physicochemical properties such as morphology, size distribution, zeta potential, entrapment efficiency, drug loading and drug release in vitro were evaluated. RESULTS: The obtained nanoparticles were spherical under transmission electron microscope. The mean diameter was 212.1 nm, the zeta potential was - 14.65 mV, the mean entrapment efficiency was 82.4% and the mean drug loading was 0.97%. The total drug release was 30% in 2 hours followed by a slow and sustained release in vitro. CONCLUSION: The optimal Api-NLCs show stable characteristics and broad prospects for application.

[Preparation and characterization of curcumin polybutylcyanoacrylate nanoparticles].

OBJECTIVE: To prepare curcumin polybutylcyanoacrylate nanoparticles (Cur-PBCNs) and evaluate its characteristics. METHODS: Cur-PBCNs were prepared by emulsion polymerization, and the formulation was optimized by L16 (4(3)) orthogonal design test with entrapment efficiency and drug loading as indices. In addition, its characteristics were investigated. RESULTS: The nanoparticles were spherical in appearance under transmission electron microscope (TEM). The mean diameter of the nanoparticles was 93.8 nm, the mean entrapment efficiency was (50.4 +/- 2.2)%, the mean drug-loading was (33.5 +/- 0.9)% and the Zeta potential was -6.81 mV. The total drug release was 34.74% in 2 hours followed by a sustained release in vitro for Cur-PBCNs, and the in vitro release profile of the nanoparticles was fit for two phases kinetics equation: 100 - Q = 4.5235e(-0.1724t) + 4.1641e(-0.0114t). CONCLUSION: The optimal Cur-PBCNs show good characteristics and sustained release character in vitro.

Endothelial nitric oxide synthase polymorphisms and erectile dysfunction: a meta-analysis.

INTRODUCTION: Erectile dysfunction (ED) is a common disorder noted for affecting quality of life. Several studies have reported the influence of endothelial nitric oxide synthase (eNOS) polymorphisms on ED susceptibility. However, results of association studies with individually low statistical power are conflicting. AIM: Our study aimed to carry out a meta-analysis estimating the association between eNOS variants and the risk of ED. METHODS: Studies regarding the association between eNOS polymorphisms and ED were searched in Medline and Embase databases. The relevant studies that met the inclusion criteria were eligible for the analysis. MAIN OUTCOME MEASURES: Five genetic models and a generalized odds ratio (OR(G) ) were used to estimate the association between eNOS G894T and variable number of 27-bp tandem repeats in intron 4 (4 VNTR) and the risk of ED. RESULTS: Nine articles were included in our meta-analysis. Overall, significant association between the 894T variant and an increased risk of ED was derived for all genetic contrasts except for the recessive model (allele contrast: OR = 1.64, 95% confidence interval [CI]: 1.03-2.60). The meta-analysis based on the OR(G) also produced significant results: OR(G) = 1.64, 95% CI: 1.03-2.61. Significant heterogeneity and publication bias were detected. The cumulative meta-analysis showed the OR increased from 2003 to 2009 and then declined in 2010. Instability in the relative change of OR was observed. Regarding 4 VNTR and its association with ED, the overall analysis showed a lack of significant association (OR = 0.96, 95% CI: 0.72-1.28). No evidence for heterogeneity among studies was observed. Subgroup analysis by ethnicity and recruitment strategy also yielded nonsignificant results. CONCLUSION: The result supports that G894T variant is associated with an increase in the risk of ED. No evidence for a significant association between 4VNTR and ED is observed. The results of the present meta-analysis should be interpreted with caution. Further confirmation in large and well-designed studies is needed.

[Preparation and characterization of curcumin loaded gelatin microspheres for lung targeting].

OBJECTIVE: To study the preparation technology and physicochemical characterization of curcumin loaded gelatin microspheres for lung targeting. METHODS: Curcumin loaded gelatin microspheres for lung targeting were prepared by the emulsion crosslinking method, and the preparation technology was optimized by orthogonal experimental design with biodegradable gelatin as the carrier, liquid paraffin as the oil phase, span 80 as the emulsifier. RESULTS: The optimal curcumin loaded gelatin microspheres were global with smooth surface, 6.15% for the drug loading, 75.5% for the encapsulation efficiency. 86.6% of microspheres size was in the range of 5-30 microm. The release test in vitro showed that 50% of curcumin could release from gelatin microspheres in 22 h and 77% in 48 h. CONCLUSIONS: The preparation technology is good and stable, and the obtained microspheres can control the release of curcumin.

[An investigation on formation mechanisms and preparation of curcumin phospholipid complex].

The purpose of this study was to investigate the preparation and characteristics of curcumin phospholipid complex, including the effects of reaction time, reaction solvent, reaction concentration and reaction temperature. Preparation technology resulted in that 0.5 g curcumin and 10 g soy phospholipid dissolved in 100 mL anhydrous alcohol, were stirred 1 h in 50 degrees C waterbath, then steamed alcohol in decompression, collected solid residue and vacuum dried for 12 h. The physicochemical properties for the new complex including IR spectrometer, mass spectrograph and HNMR equipment were detected. As a result, the formation of the complex is based on the reaction between phospholipid polar group rounding phosphorus atom and curcumin. This result gave the evidence for the formation mechanism of phospholipid complex.

[Preparation of puerarin liposome and its oral absorption in rat].

OBJECTIVE: To prepare puerarin liposome and study its oral absorption in rat. METHODS: Liposome was prepared through the way of film dispersion-ultrasonic. Free puerarin in liposome suspension was separated from liposome through ultrafiltration, and then encapsulation ratio of liposome was determined. Micro-morphology of liposme particles was observed under electronic transmission microscope. Puerarin concentration in blood was determined by HPLC. RESULTS: The encapsulation ratio of puerarin in liposome was 53%, and liposome particles were global or elliptical. The diameter range of liposome particies was from 50 nm to 300 nm. The relative availability of puerarin liposme suspension to puerarin solution was 168%. CONCLUSION: Liposome as a drug carrier can enhance the oral absorption of puerarin in rat.

[Preparation and characterization of chitosan coated puerarin liposomes].

OBJECTIVE: To prepare chitosan coated puerarin liposomes and investigate their physicochemical properties. METHODS: Puerarin liposomes were prepared by reverse phase evaporation technique and then coated with chitosan. Using encapsulation efficiency as index of examination and designing an orthogonal experiment, the optimal formulation of liposomes was determined. The physicochemical properties of uncoatd and chitosan coated puerarin liposomes were investigated, respectively. RESULTS: Uncoated and chitosan coated puerarin liposomes were spherelike and smooth. The mean particles size of uncoated and coated liposomes were 217. 3nm and 632. 6nm, respectively. The Zeta potential were -14.44 mV and +35.61 mV, respectively. The encapsulating efficency was 50. 6% and 51.1%, respectively. CONCLUSION: Puerarin liposomes can be prepared by reverse phase evaporation technique successfully. The chitosan coated purarin liposomes ware spherelike and smooth.

[Preparation and characterization of solid lipid nanoparticles of norcantharidin].

OBJECTIVE: To prepare and characterize the solid lipid nanoparticles containing norcantharidin. METHODS: Entrapment efficiency was studied to choose the best method of preparing norcantharidin solid lipid nanoparticles. The physico-chemical properties of norcantharidin solid lipid nanoparticles were investigated. RESULTS: The entrapment efficiency of norcantharidin in solid lipid nanoparticles was 54.6%, the average particle diameter was 190 nm, and it was stable at 4 degrees C for 3 months. CONCLUSION: Solid lipid nanoparticles of norcantharidin prepared has high entrapment efficiency and good stability.

[Preparation of puerarin solid self-microemulsion].

OBJECTIVE: To prepare puerarin solid self-microemulsifying drug delivery system (SMEDDS). METHODS: Pseudo-ternary phase diagram was used to select the formula of microemulsion. The self-microemulsification efficiency was assessed, such as viscosity, conductance, refraction, zeta potential, size ditribution, dissolution were investigated. Puerarin were determined by UV to calculate the cumulative release at different time. RESULTS: The optimum formulation of puerarin solid self-microemulsifying drug delivery system the consisted of puerarin-Tween 800 glycerinum-ethyl oleate-water-Gum Acacia-manicol at weight ratio of 1.7: 16. 6: 16. 6: 16. 6 : 1.3: 4.0: 39.9: 19.9; Average particle diameter was 30 nm; The dissolution was 94.29% at 10 min. CONCLUSION: Stability of puerarin solid self-microemulsion drug delvery system is good, potent in improving the dissolution of puerarin.