ABSTRACT
Aim Poly (methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) (PEGPHDCA) and PHDCA niosomes were prepared and the influence of the PEG chain length on the niosomes physicochemical characteristics, complement consumption and phagocytic uptake were studied. Methods The physicochemical parameters of PEG-PHDCA niosomes were characterized in terms of particle size, zeta potential, surface PEG density and fixed aqueous layer thickness. The relationship between physicochemical characteristics and in vitro complement consumption and phagocytic uptake was further illustrated. Results Experimental results showed that PEG10000-PHDCA had most loose structure and least PEG surface density among three groups. Configuration simulation through fixed aqueous layer thickness confirmed that PEG folding and less flexibility of the PEG chains of PEG10000-PHDCA niosomes were accountable for its poor stealth effects. Compared with PEG2000-PHDCA, PEG5000-PHDCA showed a thicker fixed aqueous layer (FALT) of 4. 20 nm, less negative zeta potential of -10.03 mV, and consumption and phagocytic uptake. Conclusion Excessive chain length of PEG was not necessary for stealth effects of PEG-PHDCA niosomes. PEG5000-PHDCA niosomes had best effects on evading complement consumption and subsequent phagocytic uptake.
ABSTRACT
Purpose To evaluate the relative bioavailability of a domestic sustained-release metformin tablets (SRM) compared against an immediate-release metformin tablets (IRM) using a multiple-dose,two-way crossover design after a single-dose study. Methods Eighteen healthy adult male volunteers,aged 18 to 22 years (mean,20 years),weighing 55 to 76 kg (mean,64 kg) and with height ranging from 166 to 180 cm (mean,173 cm),and blood glucose levels from 4.0 to 5.9 mmol/L (mean,4.3 mmol/L) participated in the study.The concentrations of metformin in plasma were determined using a ion-pair liquid chromatographic method. Results In single-dose study,the mean residence time (MRT),Tmax,and apparent elimination half-life (T1/2) for SRM were significantly longer and Cmax significantly lower than the corresponding values determined for IRM.The similar results were also demonstrated in multiple-dose study.The mean values of the relative bioavaibility of SRM compared with IRM in two administration ways were (85.95±0.97)% and (86.44±7.88)%,respectively.The single-dose and multiple-dose administration of the 90% confidence interval for the ratio of the logarithmic transformed AUC values of SRM over those of IRM were calculated to lie between 0.83 and 0.88,0.83 and 0.89,respectively,being within the acceptable bioequivalence limit of 0.80～1.25. Conclusion SRM was of the characteristic of sustained-release pharmacokinetics.The relative bioavailability for single dosing was similar to that of multiple dosing,and both of the administration ways demonstrated bioequivalence in absorption between SRM and IRM.