Studies On The Oral Absorption Of Solid Lipid Nanoparticles Loading Salvianolic Acid B

Salvianolic acid B(SalB)has a significant effect to cardiovascular disease on injection,while without oral absorption nearly.In this study,salvianolic acid B,chosen as the model drug,was mixed with phospholipid of from salvianolic acid B-phospholipid complex by ionic interaction.Solid lipid nanoparticles(SLN)were prepared by solvent diffusion containing salvianolic acid B-phospholipid complex and monoglyceride.The results showed that The results indicated that salvianolic acid B and phospholipid successfully formed complexes when the mass ratio of salvianolic acid B and phospholipid were 1 to 2.The SLNs were characterized according to morphology,particle size,size distribution,and amount of encapsulated drug.The the particle size and form of SLN was determined with Zetasizer and transmission electron microscopy(TEM).The result showed that the particle size was approximately 100 nm when the mass ratio of salvianolic acid B was 10%with the decreases in the particle size as content of salvianolic acid B increases.However,the SLN with the mass ratio of salvianolic acid B was20%had the highest loading dosage.The SLN with polyethylene goycol(PEG)modification had smaller particle with a particle size of about 60 nm,which EE%was approximately 72.15%and DL%was 16%.It showed obviously that salvianolic acid B released much slower from SLN than that diffusion for salvianolic acid B from the dialysis bag.Also the SLN with polyethylene goycol(PEG)modification had the slowest drug releasing rate which released 72.02%within 96 hours.We determined Salvianolic acid B solution and the drug-containing 10%(SLN-10%),20%(SLN-20%),30%(SLN-30%)of solid lipid nanoparticles and 10%polyethylene glycol modified SLN(pSLN-20%)in rat plasma after an oral administration.The bioavailability respectively 6.32%,81.21%,123.83%,47.57%,753.98%compared to Salvianolic acid B in rats administration by injection,indicating polyethylene glycol-modified to increase oral bioavailability.Compared to Salvianolic acid B in rats administration by injection,the mean residence time of SLN-20%and pSLN-20%from 2.04 hours,respectively increased to 14.97 hours and 36.21 hours.The results showed that solid lipid nanoparticles by PEG modification can significantly increase drug transport efficiency,prolong the retention time of the drug in vivo,reduced drug elimination rate,can greatly improve the oral bioavailability of Salvianolic acid B.Cytotoxicity knot results show:Salvianolic acid B had certain role in promoting and enhancing on cell growth with the increasing concentration.The blank SLN without salvianolic acid B has certain inhibition of cell growth,but not obvious.we can concluded that SLN has no cytotoxicity.The transmembrane transport study was performed using MDCK cell.The results showed that the transfer rate of SLN-10%,SLN-20%,SLN-30%was respectively 0.31 × 10-5cm/s,0.54 × 10-5cm/s,0.80 ×10-5cm/s,0.51 × 10-5cm/s),faster than the salvianolic acid B solution(0.31 x 10-5cm/s).It explaned that soluble drug salvianolic acid B with phospholipid complex through the ion complex method entrapped by solid lipid nanoparticles can accelerate transmembrane transport.Also the transport rate showed SLN-20%>SLN-10%>SLN-30%,and PEG-modified to improve the rate of transport,where in pSLN-20%of 0.94 × 10-5cm/s greater than SLN-20%of 0.54 × 10-5cm/s.It can alter the surface properties of SLN with appropriate modifications,more likely to be taken up by cells and enhancing membrane transport efficiency.the drug uptake rate pSLN-20%>SLN-10%>SLN-30%,explained that the uptake and transport rate were connected with the content of solid particle content of lipid material and the particle size.