Research On The Microparticles Composed Of Chitosan And Liposomes For Drug Carriers

As drug carriers,liposomes possesses the capability of target and sustained-release in some degree.It could reduce the drug dose,extenuate drug toxicity and enhance the stability of drugs.Howerer,the problem of convertional liposomes such as larging microparticle size,flocculation, leakage of drugs during the storage limits its widely application.Chitosan is a kind of polysaccharide with positively charged,which is obtained by deacetylation of chitin.It has the characteristic of hydrophilic,excellent biocompatibility,biodegradability and low toxicity and so on.Liposomes, after modified with chitosan,not only can protect the drugs,promote its permeability and raise its sustained-release,but also can increase the ability of target.Besides,it can lower the toxicity of cationic liposomes.Thus, microparticles composed of chitosan and liposomes may be a preeminently potential drug carrier.In the present research,we studied the preparation of the microparticles composed of chitosan and liposome,and took a preliminary investigation for the physical and chemical properties firstly.The results showed that the LP-CS and CS-LP,prepared by the reverse phase evaporation and the drip method respectively,had regular morphology and homogeneous size.Compared with the blank liposomes,the composite microparticles had smaller size,with the zeta potential varied from negative to positive.The disappearing of c=o(1736.6 m^-1) and p=o(1169.3 m^-1) on the infrared absorption patterns showed that the liposomes were modified by chitosan successfully.Cytotoxicity experiments in vitro showed that,the toxicity of composite microparticles reduced significantly compared with chitosan.Then,we studied the preparation of microparticles coated by chitosan and drug-containing liposomes where the fluorescent red GG was regarded as the model drug,and investigated the behavior of its cellular uptake.The result indicated that,the uptake rate of the fluorescent red GG enhanced dramatically when the composite microparticle was employed as drug carrier.Free fluorescent red GG suspension almost couldn't be intaken to the cell.After the package of liposomes(LP-GG),the fluorescence intensity increased transparently,and then coated with chitosan (CS-LP-GG),the intensity enhanced further.The increase of intracellular fluorescence intensity had a satisfactory dose-dependent manner.The results of uptake kinetics demonstrated that,the amount of the fluorescent red GG uptaked by cells was linear-increasing with the time up going in 120 min.Finally,we studied the characteristic of the microparticles composed of chitosan and liposomes as the carrier of oligonucleotide(ODN).Gel retardation adoption experiments show that,individual liposomes could't absorb ODN,while the microparticles containing CS could adsorb ODN in varies percents.The uptaken experiments indicated that,the free ODN hardly could be uptaken,and the effect of blank LP was infinitesimal,with CS for the carrier,the uptaken fluorescent amount enhanced evidently. After composited with liposomes,the introcellular fluorescence increased further with a excellent carrier concentration-dependent manner,which the concentration of 100μg/mL showed the best effects.The results of uptake kinetics proved that,the uptake of ODN increased with the time up and inclined to balance in 340 min.The uptake rate of composite microparticles was obviously faster than chitosan.Uptaken mechanism experiment showed that,the introcellular fluorescence enhanced significantly in present of chloroquine,implying that the uptaken ODN was located in lysosome,and ODN was uptaken though endocytosis.