| Andrographolide is a diterpenoid lactone and it is the main active ingredient inthe Andrographis Herba, which has a reputation of natural antibiotic on the anti-tumorand immunomodulatory effects. It is a great potential drug as it shows great inhibitoryeffect on the lung cancer, stomach cancer, colorectal cancer and other cancers, but itspoor water solubility and low dissolution resulting in the low bioavailability, whichgreatly restricted its development.Mesoporous silica nanoparticles (MSNs) is a new kind of drug carriers in recentresearch, it has high specific surface area, large pore volume, good biocompatibilityand low cost, and it can be used to improve the poorly soluble drugs dissolution byloading them. Andrographolide has been loaded on the MSNs to improve the oralbioavailability by increasing the dissolution surface and improving the dissolution rate.The main contents and results of this study are as follows:MSNs were prepared with NaOH as a catalyst, CTAB as a template, TEOS as asilicon source and water as a dispersant. The MSNs were Characterized by the N2adsorption, SEM, TEM and particle size distribution, and the effects of differentstirrer and template methods were investigated. The MSNs had been prepared with auniform size and good roundness whose diameter was about100nm.The physicochemical properties of andrographolide were investigated as thefoundation for the preparation of MSNs-AND. The results showed that the solubilityof andrographolide in different organic solvents were methanol (14.21mg·mL-1)>n-butanol (8.17mg·mL-1)> ethanol (7.58mg·mL-1)> ethyl acetate (2.43mg·mL-1)>n-octanol (1.26mg·mL-1)> chloroform (0.33mg·mL-1); The maximum amount ofdissolution of andrographolide in hot ethanol at60℃was20mg·mL-1, and itincreased as temperature increased; The solubility of andrographolide in aqueoussolutions of different pH values was lower than62μg·mL-1; under acidic conditionsthe andrographolide was relatively stable within48h, but the accumulationdegradation amount at pH10was16.25%. These results indicated thatandrographolide had poor water solubility and lipophilicity, and it was stable in anacid solution, but it would be degraded in an alkaline solution. Andrographolide was Loaded on the mesoporous silica nanoparticles and thedifferent dosages of drug content were investigated. Nitrogen adsorption, SEM, DSCand XRPD were used for characterization. The results showed that the content of thedosage of10%,20%,25%and30%(i.e., MSNs-AND (10), MSNs-AND (20),MSNs-AND (25), MSNs-AND (30)) were6.89%,14.8%,19.6%and22.3%. Afterloaded, the dispersion of the sample was more uniform, but there were no significantchanges in its appearance and size. But after loaded, the specific surface area, porevolume and pore size were reduced. Combined with the DSC and the XRD, the resultsshowed that the drug was successfully loaded into the mesoporous silica nanoparticles,but the characteristic peaks of the dosage of30%was still obvious, indicating that itwas beyond the loading capacity of the material.The dissolution of the MSNs-AND was studied and the cumulative dissolutionpercentage was calculated. By visual analysis and SPSS software processing, theresult indicated that the dissolution of the MSNs-AND was higher than theandrographolide APIs and the difference was significant; the release profile of theMSNs-AND (25) was better than other formulations and it was fit to the dissolutionequation. The results showed that it was best described by the Weibull model.In conclusion, the andrographolide we have been successfully loaded in MSNsand proved that its dissolution have been improved significantly compared to the APIthrough experiments. |
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