Effect of Binary Organic Solvents Together with Emulsifier on Particle Size and In vitro Behavior of Paclitaxel-Encapsulated Polymeric Lipid Nanoparticles.

BACKGROUND: Biodegradable nanoparticles with diameters between 100 nm and 500 nm are of great interest in the contexts of targeted delivery. OBJECTIVE: The present work provides a review concerning the effect of binary organic solvents together with emulsifier on particle size as well as the influence of particle size on the in vitro drug release and uptake behavior. METHODS: The polymeric lipid nanoparticles (PLNs) with different particle sizes were prepared by using binary solvent dispersion method. Various formulation parameters such as binary organic solvent composition and emulsifier types were evaluated on the basis of their effects on particle size and size distribution. PLNs had a strong dependency on the surface tension, intrinsic viscosity and volatilization rate of binary organic solvents and the hydrophilicity/hydrophobicity of emulsifiers. Acetone-methanol system together with pluronic F68 as emulsifier was proved to obtain the smallest particle size. Then the PLNs with different particle sizes were used to investigate how particle size at nanoscale affects interacted with tumor cells. RESULTS: As particle size got smaller, cellular uptake increased in tumor cells and PLNs with particle size of ~120 nm had the highest cellular uptake and fastest release rate. The paclitaxel (PTX)-loaded PLNs showed a size-dependent inhibition of tumor cell growth, which was commonly influenced by cellular uptake and PTX release. CONCLUSION: The PLNs would provide a useful means to further elucidate roles of particle size on delivery system of hydrophobic drugs.

Cardiac-protective effects and the possible mechanisms of alatamine during acute myocardial ischemia.

Alatamine is a constituent in the extract of a traditional herbal medicine Ramulus euonymi widely used for cardiac protection. However, its precise effects remain unclear. In the present study, we found that alatamine was able to reduce acute myocardial ischemia (AMI)-induced cardiac dysfunction in a rat model, as reflected by significantly restored electrocardiograms, M-mode echocardiograms, and left ventricular hemodynamics. Also, Nagar Olsen staining revealed that alatamine markedly reduced AMI-induced cardiac injury and cardiac myocyte apoptosis. TUNEL and caspase-3 activity assay showed that cardiac myocytes underwent significant apoptosis during AMI, and levels of LDH and CK-MB increased in the serum. However, such changes were significantly inhibited by pre-administration of alatamine. Furthermore, such anti-apoptotic effects of alatamine was also confirmed in a cardiac myocyte model of isoproterenol (ISO)-induced damage. Mechanistically, it was also found that alatamine improved the expression and activity of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA), which were inhibited during AMI, promoting contractility and relaxation. Meanwhile, alatamine decreased Bax and increased Bcl-2 expressions both in vivo and in vitro, therefore inhibiting cardiac myocyte apoptosis and preventing cardiac dysfunction caused by AMI at the cellular level. The present study revealed the beneficial role of alatamine in cardiac protection and highlighted it as a potential therapeutic reagent for reduction of AMI-induced cardiac injury.