Studies On Liposome Entrapped Andrographolide Inclusion Complex Targeting Drug Delivery System

Andrographolide has many pharmacological actions such as antibiosis, relieving fever,anti-inflammatory, antivirus, antineoplastic, hepatic protecetant and cholagogic. In clinicliposome is widely applied for treating pneumonia, common cold, upper respiratory tractinfection, cardiovascular diseases, bacillary dysentery and so on. In recent years, theantineoplastic action of andrographolide has been broadly researched. However, because of thepoor solubility and extremely bitterness, it is limited in clinical application. Besides, the formsof andrographolide are just stay at capsule and troche and so on; the studies of long-circulatingand targeting drug delivery system are far behind.Liposome targeting drug delivery system is a significant and hot topic in modernpharmaceutics field. Liposome is a kind of drug delivery system which is composed byphospholipids and cholesterol. Liposome could be easily degrading in vivo and usually haveno toxicity. The bilayer structure of liposome could make both entrap lipid solubility and watersolubility drugs. Also liposome has nice histocompatibility and cellular affinity, but liposomehas no immunogenicity. Besides the targeting and delayed releasing advantages, liposomecould be embellished and could have initiative targeting and long circulating characters.Studying on liposome entrapped andrographolide inclusion complex targeting drug deliverysystem could improve the absorption and clinical effectiveness.However, the liposome drug delivery system is not stable and low drug-loading ratebecause of the poor solubility of andrographolide. For that, we design andrographolide andHP-β-CD supramolecular inclusion complex to increase solubility. Then we makeandrographolide-HP-β-CD supramolecular inclusion complex entrapped in liposome.Liposome entrapped andrographolide inclusion complex targeting system not only solve thestability and drug-loading rate of liposome, but also keep the targeting and controlled-releaseadvantages of liposome. When developing the drug delivery system we connect PEG on thesurface of liposome that prolong the in vivo circling time, in order to further increase thebioavailability of andrographolide.Our study could divide into three parties: firstly, we study on andrographolide-HP-β-CDsupramolecular inclusion complex; secondly, we develop the liposome entrappedandrographolide-HP-β-CD supramolecular inclusion complex targeting drug delivery system; at last, we study on the targeting of drug delivery system on rats.In the first part of the study, we use the results of phase solubility test are that thesolubility of andrographolide is obviously increased in HP-β-CD aqueous solution; the rate oftwo molecular in the supramolecular is1:1. The preparation is aqueous solution. Theentrapment rate of andrographolide-HP-β-CD supramolecular inclusion complex is92.7%.X-ray, IR, and NMR spectroscopy were used to confirm the formation of theandrographolide-HP-β-CD supramolecular, and the results infer that guest molecules enter intothe HP-β-CD molecules from their bigger side of the cavity structure. The solubility ofandrographolide has been obviously increased by HP-β-CD.In the second part of the study, the preparation of liposome entrapped andrographolide-HP-β-CD supramolecular inclusion complex method is diaphragm ultrasound. The entrapmentrate is87.9%and the drug-loading rate is10.8%by using HPLC; the diameter is445.8nm;Zeta-potential is-10.33mV. After presering freeze-drying powder60days, the diameter is445.8nm; Zeta-potential is-10.33mV; the drug-loading rate is10.8%. The results show thatthe drug delivery system is stable. The structure of liposome entrapped andrographolide-HP-β-CD supramolecular inclusion complex should be that the supramolecular inclusioncomplex is in the hydrophile room of the liposome; the added crude andrographolide shouldbe in the hydrophobic bilayer structure of liposome. For that the drug-loading rate is raisedand the system is stable.In the third part of the study, we use HPLC to constitute the analyzing method. Theliposome entrapped andrographolide-HP-β-CD supramolecular inclusin complex is tailintravenous injected into rats. The results show that after injected andrographolide parenteralsolution, the Andrographolide is mainly distributing in liver, spleen, kidney andgastrointestinal tract. Meanwhile after injected the liposome entrapped andrographolide-HP-β-CD supramolecular inclusion complex, the target tissue is lung. And the concentration ofandrographolide in lung is obviously higher than in other tissues. After injected36h, theandrographolide could still be tested in lung and plasma. The reason is that the liposomeconnected with PEG. That obviously prolong the circulating time in vivo, and make drugdelivery system has excellent long residual action.In this study, we make andrographolide as object drug, and develop liposome targetingdrug delivery system combined the inclusion complex and liposome. The drug delivery systemnot only solve the forming drug, stability and drug-loading rate of andrographolide liposome,but also keep the targeting and long-circulating advantages of liposome. When developing the drug delivery system we connect PEG on the surface of liposome that prolong the in vivocircling time, in order to further increase the bioavailability of andrographolide.