Transport of mPEG-PLGA nanoparticles across the rat nasal mucosa / 药学学报

To investigate the effects of particle size, mPEG molecular weight, coating density and zeta potential of monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles on their transportation across the rat nasal mucosa, mPEG-PLGA-NPs with different mPEG molecular weights (M(r) 1 000, 2 000) and coating density (0, 5%, 10%, 15%) and chitosan coated PLGA-NP, which loaded coumarin-6 as fluorescent marker, were prepared with the nanoprecipitation method and emulsion-solvent evaporation method, and determine their particle size, zeta potential, the efficiency of fluorescent labeling, in vitro leakage rate and the stability with the lysozyme were determined. The effects of physical and chemical properties on the transmucosal transport of the fluorescent nanoparticles were investigated by confocal laser scanning microscopy (CLSM). The result showed that the size of nanoparticles prepared with nanoprecipitation method varied between 120 and 200 nm; the size of nanoparticles prepared with emulsion-solvent evaporation method varied between 420 and 450 nm. Nanoparticles dispersed uniformly; the zeta potential of PLGA-NPs was negative; mPEG-PLGA-NPs was close to neutral; chitosan coated PLGA-NPs was positive; and the efficiency of fluorescent labeling were higher than 80%. In vitro leak was less than 5% within 4 h and nanoparticles were basically stable with lysozyme. The CLSM results show that the transportation efficiency of mPEG-PLGA-NPs with a high PEG coating density and high mPEG molecular weight was significantly higher than that of uncoated PLGA nanoparticles and also that of chitosan coated PLGA-NPs (P < 0.05). The hydrophilcity, zeta potential and particle size of nanoparticles play important roles on the efficiency of mPEG-PLGA nanoparticles to transport across the rat nasal mucosa.

Transport of PLGA nanoparticles across Caco-2/HT29-MTX co-cultured cells / 药学学报

The present study is to establish Caco-2/HT29-MTX co-cultured cells and investigate the transport capability of PLGA nanoparticles with different surface chemical properties across Caco-2/HT29-MTX co-cultured cells. PLGA-NPs, mPEG-PLGA-NPs and chitosan coated PLGA-NPs were prepared by nanoprecipitation method using poly(lactic-co-glycolic acid) as carrier material with surface modified by methoxy poly(ethylene glycol) and chitosan. The particle size and zeta potential of nanoparticles were measured by dynamic light scattering. Coumarin 6 was used as a fluorescent marker in the transport of nanoparticles investigated by confocal laser scanning microscopy. The transport of furanodiene (FDE) loaded nanoparticles was quantitively determined by high performance liquid chromatography. Colchicine and nocodazole were used in the transport study to explore the involved endocytosis mechanisms of nanoparticles. Distribution of the tight junction proteins ZO-1 was also analyzed by immunofluorescence staining. The results showed that the nanoparticles dispersed uniformly. The zeta potential of PLGA-NPs was negative, the mPEG-PLGA-NPs was close to neutral and the CS-PLGA-NPs was positive. The entrapment efficiency of FDE in all nanoparticles was higher than 75%. The transport capability of mPEG-PLGA-NPs across Caco-2/HT29-MTX co-cultured cells was higher than that of PLGA-NPs and CS-PLGA-NPs. Colchicine and nocodazole could significantly decrease the transport amount of nanoparticles. mPEG-PLGA-NPs could obviously reduce the distribution of ZO-1 protein than PLGA-NPs and CS-PLGA-NPs. The transport mechanism of PLGA-NPs and mPEG-PLGA-NPs were indicated to be a combination of endocytosis and paracellular way, while CS-PLGA-NPs mainly relied on the endocytosis way. PEG coating could shield the surface charge and enhance the hydrophilicity of PLGA nanoparticles, which leads mPEG-PLGA-NPs to possess higher anti-adhesion activity. As a result, mPEG-PLGA-NPs could penetrate the mucus layer rapidly and transport across Caco-2/HT29-MTX co-cultured cells.

The study of MePEG content and chain density on MePEG-PLGA-NP surface with 1H-NMR method / 中国药学杂志

OBJECTIVE: 1H-NMR (Nuclear Magnetic Resonance Method) was used to quantitatively determine the MePEG (me-thoxy polyethylene glycol) content and chain density on MePEG-PLGA-NP surface, and study the influences of MePEG molecular weights and proportion on the chemical and physical properties of MePEG-PLGA-NP surface. METHODS: MePEG-PLGA-NP were prepared by self-emulsion solvent diffusion method with methoxy polyethylene glycol-poly(lactic acid-hydroxyl acid) copolymer (Me-PEG-PLGA) as the carriers. And the particle average size and Zeta potential were characterized. 1H-NMR method were used to ascertain the composition of the MePEG-PLGA copolymer and determine the MePEG content and chain density on the MePEG-PLGA-NP surface, and compared with colorimetric assay. RESULTS: The composition of MePEG-PLGA copolymer are basically the same with the labelled amount. When the Molecular weight is at the same, along with the increase of proportion of MePEG, the average size of MePEG-PLGA-NP decrease, the absolute value of the Zeta potential also decrease gradually, MePEG content on particles surface (α) increase gradually, the MePEG chain density on nanoparticles surface (δ) increase gradually, the distance between two adjacent MePEG chains on the surface of the particles (D) decrease; When there is the same proportions, with MePEG chain length increases, nanoparticles are not significantly different on the particle average size and the Zeta potential, whereas α increase gradually, the δ decreases, and D increases; Theavalue of the same MePEG-PLGA-NP determined by colorimetric assay is higher than which is determined by 1H-NMR. CONCLUSION: 1H-NMR method can be used to quantitatively determine the MePEG content and chain density on MePEG-PLGA-NP surface; Compared with the traditional method, the results determined by 1H-NMR method are more accurate. With the experimental limits, MePEG molecular weighs and proportion have influences on the chemical and physical properties of MePEG-PLGA NP surface, such as mean size, Zeta potential and the MePEG content and chain density on nanoparticles surface. Copyright 2012 by the Chinese Pharmaceutical Association.