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The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin (DOX)-loaded methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration; DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. Hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.
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Objective: To prepare charge-reversal pH-sensitive nanoparticles loaded with curcumin (PCE/Cur NPs), and investigate the optimizing technology, physicochemical characterizations, and inhibitory effect on B16 cell. Methods: The β-carboxyl amidized cationic MPEG-PCL-PEI polymers (PCE) were negatively charged, which were prepared into the negative PCE/Cur NPs with pH dependence. When pH > 7, there was no charge-reversal. When pH < 6, the β-carboxyl amides were hydrolyzed rapidly into corresponding amines. As a result, PCE/Cur NPs became positively charged again. The obtained PCE/Cur NPs were characterized by detection of particle size, morphology study, drug loading, encapsulation efficiency, and release study. The effect of anti-migratory and anti-invasive actions of PCE/Cur NPs on B16 cell was investigated using MTT assays and wound healing test. Results: PCE/Cur NPs dependent on pH charge inversion were successfully prepared. The obtained PCE/Cur NPs were round, and the size was uniform, the adhesion was not found. The Results: showed that the prepared PCE/Cur NPs had the highest DL (8.0 ± 1.0)%, EE (90.0 ± 2.0)%, mean particle size of (80 ± 5) nm, and zeta potential of (-35 ± 5) mV. Within 48 h, the accumulative release rate was (69.2 ± 5.2)% (pH 7.4) and (71.2 ± 4.3)% (pH 5), respectively, and then PCE/Cur NPs released slowly. These Results: by MTT assay and wound healing assay indicated that PCE/Cur NPs not only inhibited the proliferation of B16 cells in a concentration- and time-dependent manner, but also can induce apoptosis. Conclusion: PCE/Cur NPs were prepared successfully, which might have great potential application in drug delivery system.
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OBJECTIVE: To determine the effects of the amphiphilic block polymers, which have the same hydrophilic block with the different hydrophobic block, on the function of P-glycoprotein(P-gp). METHODS: The three different micelles were prepared by film dispersion method. The particle sizes and distributions were measured by dynamic light scattering. Critical micelle concentrations(CMC) were detected by fluorescence probe technique with the pyrene. Rhodamine 123, a specific probe substrate of P-gp, was applied to determine the effects of polymers on the function of P-gp using uptake and efflux method. RESULTS: The particle sizes of mPEG-PCL, mPEG-PDLLA, mPEG-PLGA were (55.9±0.2), (53.7±1.1) and (61.6±0.6)nm. The CMC values were 2.08, 5.42 and 26.4 μg·mL-1. R123 accumulation in Madin-Darby canine kidney/multidrug resistance 1(MDCK-MDR1)cell detected by uptake assay increased to a maximum in the presence of polymers at concentrations of 250 μg·mL-1 for mPEG-PCL, 1~25 μg·mL-1 for mPEG-PDLLA and mPEG-PLGA. In efflux assay, mPEG-PCL, mPEG-PDLLA, mPEG-PLGA decreased the percentage of efflux of R123 at concentrations above the CMC, below/at the CMC or below the CMC respectively, showed the similar RESULTS with uptake assay. CONCLUSION: The mPEG-PCL, mPEG-PDLLA, mPEG-PLGA polymers might have a potential to inhibit the efflux activity of P-gp, which was likely related to the structures of hydrophobic segments, concentrations and existing states of the polymers.
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