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The purpose of this study was to analyze the encapsulation of superparamagnetic iron oxide nanoparticles (SPION) by the lipid nanoparticle conjugated with the 12-mer peptides (RLLDTNRPLLPY, L-peptide), and the delivery of this complex into living cells. The lipid nanoparticles employed in this work were highly hydrophilic, stable, and contained poly(ethylene-glycol) for conjugation to the bioactive L-peptide. The particle sizes of two different magnetic lipid nanoparticles, L-peptide modified (LML) and non-L-peptide modified (ML), were both around 170 nm with a narrow range of size disparity. The transversal relaxivity, r2, for both LML and ML nanoparticles were found to be significantly higher than the longitudinal relaxivity r1 (r2/r1 > 20). The in vitro tumor cell targeting efficacy of the LML nanoparticles were evaluated and compared to the ML nanoparticles, upon observing cellular uptake of magnetic lipid nanoparticles by the nasopharyngeal carcinoma cells, which express cell surface specific protein for the L-peptide binding revealed. In the Prussian blue staining experiment, cells incubated with LML nanoparticles indicated much higher intracellular iron density than cells incubated with only the ML and SPION nanoparticles. In addition, the MTT assay showed the negligible cell cytotoxicity for LML, ML and SPION nanoparticles. The MR imaging studies demonstrate the better T2-weighted images for the LML-nanoparticle-loaded nasopharyngeal carcinoma cells than the ML- and SPION-loaded cells.

In this study, we developed a nanoparticle system for drug delivery across the blood-brain barrier (BBB). The nanoparticle consisting of loperamide and poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer were prepared by the nanoprecipitation method; then the nanoparticles were coated with poloxamer 188 or polysorbate 80. The effects of poloxamer 188 or polysorbate 80 on the physicochemical and pharmaceutical properties of the coated nanoparticles were investigated. Loperamide, which does not cross the blood-brain barrier (BBB) but exerts antinociceptive effects after direct injection into the brain, was encapsulated by different polymeric materials and used as a model drug. The in vitro BBB penetration study shows that the surfactant-coated PLGA-PEG-PLGA nanoparticles could have penetration of 14.4-21.2%, which was better than the PLGA-PEG-PLGA nanoparticles (PEP) (8.2%) and the PLGA nanoparticles (PN) (4.3%). The biopsy studies also confirm that the PEP coated by surfactant could increase the penetration. The results of nanoparticles accumulation in brain tissue show that the PEP coated by surfactant had a much higher concentration than both the PEP and the PN. Moreover, the maximal possible antinociception effect (MPE) for the surfactant-coated PEP was 21-35% at 150 min after administering the drug intravenously, which was significantly better than just the PEP (MPE: 11.6%). The results of the formalin test show that the surfactant-coated PEP administered intravenously 150 min prior to the formalin injection could greatly reduce the pain response in the first phase. The results demonstrate that the surfactant-coated PEP could help to deliver loperamide across the BBB.

The multifunctional nanoparticles constructed from triphenylamine-poly(lactide-co-glycolide)-poly(ethyleneglycol)-poly(lactide-co-glycolide) (TPA-PEP) and folate-poly(2-ethyl-2oxazoline)-poly(D,L-lactide) (folate-PEOz-PLA) were developed in this study. Iron oxide nanoparticles (IOP) and paclitaxel (PTX) were coencapsulated in the nanoparticles with diameter less than 200 nm. The drug-loaded nanoparticles emit fluorescence peak at 460 nm when excited with wavelength of 350 nm. The in vitro antitumor activity of the drug-loaded nanoparticles was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays against HeLa cells. When the cells were exposed to the nanoparticles with different levels of folate but the same drug loading, cell viability decreases as the level of folate increases. Confocal laser scanning microscopy (CLSM) analysis shows that cellular uptake is lower for the non-folate-nanoparticles than that for the folate-nanoparticles. The in vitro and in vivo magnetic resonance imaging (MRI) studies indicate the better T2-Weighted images can be obtained for the folate-nanoparticles. In the anticancer effect evaluation, tumor-bearing mice administered with the 30%-folate-nanoparticles showed ~50% reduction in tumor volume after 23 days. The multifunctional nanoparticles as drug carrier with capabilities of both tumor-targeting and MRI present a new direction in drug delivery system development., (Copyright © 2012 Wiley Periodicals, Inc.)