Entrapment and release of saquinavir using novel cationic solid lipid nanoparticles.

Cationic solid lipid nanoparticles (CSLNs) with entrapped saquinavir (SQV) were fabricated by microemulsion method. Here, CSLNs were stabilized by polysorbate 80, and the lipid phase contained cationic stearylamine (SA) and dioctadecyldimethyl ammonium bromide (DODAB) and nonionic Compritol 888 ATO (CA) and cacao butter (CB). Properties of the present pharmaceutical formulations including the entrapment efficiency, the release kinetics, and the distribution of SQV in CSLNs were analyzed. The results indicated that a mixture of SA and DODAB and a mixture of CA and CB were beneficial to the entrapment efficiency of SQV. However, an increase in the content of cationic lipids insignificantly affected the entrapment efficiency of SQV when the weight percentage of SA and DODAB was greater than 1% during emulsification. Also, the rate of SQV released from CSLNs with lipid cores of a mixture of CA and CB was slower than that of pure CB. The temporal variation in the released SQV suggested that the carriers could be sustained delivery systems with no apparent initial burst. Hence, the current CSLNs could carry SQV for the improved medication of individuals infected by human immunodeficiency viruses.

Effect of nanoparticulate polybutylcyanoacrylate and methylmethacrylate-sulfopropylmethacrylate on the permeability of zidovudine and lamivudine across the in vitro blood-brain barrier.

Effect of size of nanoscaled polybutylcyanoacrylate (PBCA) and methylmethacrylate-sulfopropylmethacrylate (MMA-SPM) on the permeability of zidovudine (AZT) and lamivudine (3TC) across the blood-brain barrier (BBB) was investigated. Also, influence of alcohol on the permeability of AZT and 3TC incorporated with the two polymeric nanoparticles (NPs) was examined. The loading efficiency and the permeability of AZT and 3TC decreased with an increase in the particle size of the two carriers. By employing PBCA NPs, the BBB permeability of AZT and that of 3TC became, respectively, 8-20 and 10-18 folds. Application of MMA-SPM NPs leaded to about 100% increase in the BBB permeability of the two drugs. In the presence of 0.5% ethanol, 4-12% enhancement in the BBB permeability of the two drugs was obtained in the current carrier-mediated system.

Multifunctional hollow nanoparticles based on graft-diblock copolymers for doxorubicin delivery.

This article reports a flexible hollow nanoparticles, self-assembling from poly(N-vinylimidazole-co-N-vinylpyrrolidone)-g-poly(d,l-lactide) graft copolymers and methoxyl/functionalized-PEG-PLA diblock copolymers, as an anticancer drug doxorubicin (Dox) carrier for cancer targeting, imaging, and cancer therapy. This multifunctional hollow nanoparticle exhibited a specific on-off switch drug release behavior, owning to the pH-sensitive structure of imidazole, to release Dox in acidic surroundings (intracellular endosomes) and to capsulate Dox in neutral surroundings (blood circulation or extracellular matrix). Imaging by SPECT/CT shows that nanoparticle conjugated with folic acids ensures a high intratumoral accumulation due to the folate-binding protein (FBP)-binding effect. In vivo tumor growth inhibition shows that nanoparticles exhibited excellent antitumor activity and a high rate of apoptosis in cancer cells. After 80-day treatment course of nanoparticles, it did not appreciably cause heart, liver and kidney damage by inactive Dox or polymeric materials. The results indicate that the flexible carriers with an on-off switched drug release may be allowed to accurately deliver to targeted tumors for cancer therapy.

Effect of electromagnetic field on endocytosis of cationic solid lipid nanoparticles by human brain-microvascular endothelial cells.

This study investigates the electromagnetic field (EMF)-regulated transport of cationic solid lipid nanoparticles (CSLNs) across human brain-microvascular endothelial cells (HBMECs). The positive charge of CSLNs was from dioctadecyldimethyl ammonium bromide and stearylamine, and radiofrequency EMF was applied to HBMECs for promoting uptake of CSLNs. Immunochemical staining revealed that the expression of clathrin on the membrane of HBMECs enhanced during vesicular endocytosis of CSLNs. However, CSLNs and EMF slightly affected the expression of P-glycoprotein on the membrane of HBMECs. An exposure to EMF yielded negligible increase in the permeability of free saquinavir (SQV) across the HBMEC monolayer. Nevertheless, the permeability of SQV across the HBMEC monolayer increased about 17-fold when SQV was entrapped in CSLNs. Moreover, the permeability of SQV across the HBMEC monolayer increased about 22-fold by applying the CSLN encapsulation and EMF exposure. CSLNs and EMF could produce synergistic effect on improving the brain-targeting delivery.