ABSTRACT
@#Polyethylene glycol (PEG) of different lengths were prepared to investigate their effects on oral absorption of nanostructured lipid carrier (NLCs).Three kinds of PEG-modified NLCs with different chain lengths, including polyethylene glycol (100) monostearate (S100), polyethylene glycol (55) monostearate (S55), polyethylene glycol (40) monostearate (S40), were prepared by film dispersion method.Coumarin 6 was chosen as a fluorescent probe to characterize the physicochemical properties of NLCs with different lengths.Meanwhile, the stability of NLCs in simulate buffer, the release behavior, cytotoxicity of NLCs, the uptake kinetics and cellular uptake mechanisms were evaluated. This work demonstrated that the thickness of the hydrated layer increased with the increase of PEG length. Of note, S100-modified NLCs (pNLC-EG100) exhibited higher cellular uptake efficiency compared with other formulations. Thus, S100 was optimized as the best molecular weight for PEG-modified NLCs on oral drug delivery system.
ABSTRACT
Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs,
ABSTRACT
The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two
ABSTRACT
The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.
ABSTRACT
Objective The aim of this study was to investigate the distribution and liver-targeting properties of quercetin (QT)/coumarin 6 (C6)-loaded polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (QCPTN) in a hepatocarcinoma ectopic transplantation solid tumor model using HCa-F cell-bearing mice.Methods The QT concentrations in biological samples were determined using reverse phase-high performance liquid chromatography (RP-HPLC) analysis.After intravenous administration to mice in the QCPTN and QTS groups,the QT concentration in plasma and in different tissues was simultaneously analyzed at the different time points.Detection indexes (relative targeting efficiency,Re;targeting efficiency,Te) and fluorescence inversion microscopy images of the frozen tissue (liver,solid tumor,spleen,lungs,kidneys,and heart) slices were used for quantitatively and qualitatively evaluating the liver-targeting properties of QCPTN in solid tumor-bearing mice.Results Te of the QCPTN group in the plasma,liver,solid tumor,spleen,lungs,kidneys,and heart were all greater than 3,indicating that the area under the concentration-time curve (AUC) of liver was more than three times that of the plasma and other organs.Fluorescence inversion microscopy images showed that the green fluorescence of QCPTN was mostly observed in the liver.Conclusion Using HCa-F cell-beating mice,QCPTN was found to have better in vivo liver-targeting properties in hepatocarcinoma ectopic transplantation solid tumor.
ABSTRACT
OBJECTIVE: To establish a method for determination of the entrapment efficiency of coumarin 6-loaded PLGA nanoparticles by high-speed centrifugation. METHODS: The nanoparticle suspensions were diluted by different vehicles, and free drugs were then separated by high-speed centrifugation. The separation effect for free drug and nanoparticles as well as the effect of diluting solvent on nanoparticles morphology were observed by scanning electron microscopy. The method was validated and the determination condition was optimized. RESULTS: The calibration curve for coumarin 6 had good linearity in the range of 0.8-100 ng(r=1.000 0), and the precision were high with RSD≤1.28%. After diluting the nanoparticle suspensions with 1% TPGs, high-speed centrifugation could effectively separate the free drug from nanoparticles. The recovery of free drug was 99.25%-103.00%. The average entrapment efficiencies of coumarin 6-loaded nanoparticles was 88.74% with RSD of 0.65%. CONCLUSION: The method is rapid, accurate and feasible. It can be used to determine the entrapment efficiency of coumarin 6-loaded PLGA nanoparticles.
ABSTRACT
@#To construct nanostructured lipid carriers(NLCs)with different particle sizes but the same other physicochemical properties, central composite design was adopted. Coumarin-6(C-6)was selected as the model drug due to its high lipophilicity and high fluorescence intensity. Physicochemical properties of NLCs with 100 nm, 200 nm and 300 nm in particle size could remain stable during certain time in K-R solution and PBS. Release experiments in vitro showed that cumulative release of C-6 in NLCs was less than 7% after 24 h. The MTT assay indicated that both blank NLCs and C-6 loaded NLCs showed low toxicity. To confirm the integrity of NLCs in gastrointestinal tract, DiR-loaded NLCs were prepared and the distribution in vivo was monitored by fluorescence imaging. After 6 h oral administration, intact DiR-loaded NLCs could stiu be found, suggesting that NLCs could be used to characterize the uptake in gastrointestinal tract.
ABSTRACT
OBJECTIVE: To investigate the uptake and transport properties of micelles across Madin Darby canine kidney (MD-CK) cells. METHODS: Coumarin 6 loaded PEG-PLA (PEG3000-PLA3000) micelles were prepared by solvent evaporation method, and the HPLC determination method of coumarin 6 was constructed. Competition uptake of blank micelles with coumarin 6 micelles was studied. Temperature and inhibitors effect on transport of micelles across MDCK cell monolayer were studied, the concentration of Ca and EGTA were also studied. RESULTS: Coumarin 6 micelles could be internalized into cells very quickly, and the uptake of micelles could be inhibited by blank micelles. The transport of micelles was affected by temperature and inhibitors, which means that this process is an active and energy-dependent process. The concentration of Ca2+ and EGTA could affect the transport of the micelles, which means micelles could transport across the cell monolayer via paracellular pathway. The amount of transported coumarin 6 micelles was rather limited compared with coumarin 6 micelles added to the apical side. CONCLUSION: Micelles transport across MDCK cell monolayer via both paracellular and transcellular pathway at the same time.
ABSTRACT
OBJECTIVE: To investigate transport route of fluorescent probe following inner ear administration. METHODS: Coumarin-6 (CM) was employed as fluorescent probe and CM-loaded poly (lactic-co-glycolic acid) nanoparticles (CM-PLGA-NP) were prepared by emulsification-solvent evaporation method. Perilymph (PL), contralateral PL, cerebrospinal fluid (CSF) and plasma were collected periodically in guinea pigs after unilateral intratympanic administration of CM-PLGA-NP or CM solution. The concentrations of CM were determined by high performance liquid chromatography (HPLC), and statistic program DAS was applied to the calculation of pharmacokinetic parameters. RESULTS: CM was found in PL, contralateral PL and CSF after unilateral intratympanic administration of CM-PLGA-NP or CM solution. The AUC in PL and CSF following intratympanic administration of CM-PLGA-NP were respectively 3.7 and 7.6-fold higher than those following intratympanic administration of CM solution. And the ρmax in PL and CSF were respectively 9.9 and 9.0-fold higher. Moreover, CM-PLGA-NP extended the MRT in PL and CSF by 5.1 and 9.4 times compared with CM solution. CONCLUSION: Transport pathway of intra-cochlear administration is PL → CSF → contralateral PL. Nanoparticles can greatly improve drug distribution within the inner ear and CSF, and prolong the residence time. Copyright 2012 by the Chinese Pharmaceutical Association.