No abstract

Emerging nanotechnology has already developed various innovative nanomedicines. Nanomicelles, self-assemblies of block copolymers, are promising nanomedicines for targeted drug delivery and imaging. Stimulus-responsive targeted nanomicelles are designed to release drugs based on stimuli such as pH, temperature, redox potential, magnetism and ultrasound. This article will focus on recent advancements in the design of stimulus-responsive targeted nanomicelles loaded with anticancer drugs to fulfill the challenges associated with cancer cells (e.g., multidrug resistance) for the effective treatment of cancer. The significant toxicity issues and a possible future perspective associated with nanomicelles are also discussed here.

The aim of the present work was to design and develop Praziquantal (PZQ) loaded solid lipid nanoparticles (PZQ-SLN) to improve the oral bioavailability by targeting intestinal lymphatic system. PZQ is practically insoluble in water and exhibits extensive hepatic first-pass metabolism. PZQ SLN were composed of triglycerides, lecithin and various aqueous surfactants; were optimized using hot homogenization followed by ultrasonication method. The optimized SLN had particle size of123±3.41 nm, EE of86.6±5.72%. The drug release of PZQ-SLN showed initial burst release followed by the sustained release. Inspite of zeta potential being around −10 mV, the optimized SLN were stable at storage conditions (5±3°C and25±2°C/60±5% RH) for six months. TEM study confirmed the almost spherical shape similar to the control formulations. Solid state characterization using differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) analysis confirmed the homogeneous distribution of PZQ within the lipid matrix. The 5.81-fold increase inAUC0→∞, after intraduodenal administration of PZQ-SLN in rats treated with saline in comparison to rats treated with cycloheximide (a blocker of intestinal lymphatic pathway), confirmed its intestinal lymphatic delivery. The experimental results indicate that SLN may offer a promising strategy for improving the therapeutic efficacy and reducing the dose.

The intention of this study is to achieve higher entrapment efficiency (EE) of berberine chloride (selected hydrophilic drug) using nanoprecipitation technique. The solubility of drug was studied in various pH buffers (1.2-7.2) for selection of aqueous phase and stabilizer. Quality by design (QbD)-based 3(2) factorial design were employed for optimization of formulation variables; drug to polymer ratio (X1) and surfactant concentration (X2) on entrapment efficiency (EE), particle size (PS) and polydispersity index (PDI) of the nanoparticles. The nanoparticles were subjected to solid state analysis, in vitro drug release and stability study. The aqueous phase and stabilizer selected for the formulations were pH 4.5 phthalate buffer and surfactant F-68, respectively. The formulation (F-6) containing drug to polymer ratio (1:3) and stabilizer (F-68) concentration of 50 mM exhibited best EE (82.12%), PS (196.71 nm), PDI (0.153). The various solid state characterizations assured that entrapped drug is amorphous and nanoparticles are fairly spherical in shape. In vitro drug release of the F-6 exhibited sustained release with non-Fickian diffusion and stable at storage condition. This work illustrates that the proper selection of aqueous phase and optimization of formulation variables could be helpful in improving the EE of hydrophilic drugs by nanoprecipitation technique.

Repaglinide solid lipid nanoparticles (RG-SLN) were fabricated using stearic acid as lipid. Pluronic F68 (PLF68) and soya lecithin were used as a stabilizer. SLNs were prepared by modified solvent injection and ultrasonication methods. SLNs prepared with modified solvent injection method have larger particle size (360+/-2.5nm) than prepared with ultrasonication method (281+/-5.3nm). The zeta potential of the prepared formulations by these two methods varied from - 23.10 +/-1.23 to -26.01 +/-0.89 mV. The maximum entrapment efficiency (62.14 +/-1.29%) was obtained in modified solvent injection method. The total drug content was nearly same (98%) in both the methods. In vitro release studies were performed in phosphate buffer (pH 6.8) with 0.5% sodium lauryl sulphate (SLS) using dialysis bag diffusion technique. The cumulative drug release was 30% and 50% within 2 hrs in modified solvent injection and ultrasonication method, respectively. This indicates that RG-SLN prepared from modified injection method released the drug more slowly than SLNs prepared with ultrasonication method. Differential scanning calorimetry indicates that repaglinide (RG) entrapped in the solid lipid nanoparticles (SLN) exist in an amorphous or molecular state. Repaglinide loaded solid lipid nanoparticles prepared with both methods were of spherical shape as observed by transmission electron microscopy (TEM). These results suggest that modified solvent injection method is more suitable for preparation of repaglinide SLNs using stearic acid.