Preparation Of Modified Konjac Glucomannan Nanospheres/Microcapsules And Their Application As Drug Carriers

Konjac glucomannan(KGM),a kind of abundant polysaccharide in nature,not only has good biocompatibility and biodegradability,as well as the activities of anti-tumor,cholesterol lowering,anti-hyperglycemia,anti-inflammatory and immune regulation,thus exhibits great potential in biomedical field.In this study,KGM was chemically modified,and then prepared nanospheres and microcapsules as drug delivery carriers.Ovalbumin(OVA)was used as a model antigen to explore the impacts of nanospheres as vaccine adjuvants on immune responses in mice,and 5-aminosalicylic acid(5-ASA)was used as a model drug to explore the ability of microcapsules to encapsulate small molecules and the drug controlled release mechanism.1.KGM was firstly acid-hydrolysed to reduce its molecular weight,and then anionic carboxymethylated konjac glucomannan(CKGM)and cationic quaternized konjac glucomannan(QKGM)were synthesized by chemical modification of acid-hydrolysed KGM.Subsequently,two types of nanospheres,CKGM/QKGM and sodium tripolyphosphate(TPP)/QKGM,were prepared through polyelectrolyte complexation and ionic cross-linking methods,respectively.The thus-synthesized nanospheres were then loaded with OVA to further evaluate their effects on immune responses in mice.The encapsulation efficiency of OVA for CKGM/QKGM/OVA and TPP/QKGM/OVA nanospheres were 49.2% and 67.7%,respectively,while the drug loading capacity reached 10.9% and 60%.The nanospheres showed irregular spherical shape and exhibited good sustained-release properties.MTT assay revealed that both the blank and OVA-loaded nanospheres were not toxic to cells.The results of immune experiments in mice showed that TPP/QKGM and CKGM/QKGM nanospheres are promising to be used as vaccine adjuvants to enhance the humoral and cellular immune responses of mice.TPP/QKGM/OVA nanospheres could induce stronger humoral immune response,while CKGM/QKGM/OVA nanospheres could enhance the cellular immune response more effectively.2.CKGM/CS/TPP/5-ASA microcapsules were prepared by polyelectrolyte composite through anionic CKGM and cationic chitosan(CS)in aqueous solution using TPP as a cross-linking agent and 5-ASA as a model drug.The preparation conditions was optimized by the single factor method.When the CKGM concentration was 15 mg/mL,TPP concentration was 5 mg/mL,CS concentration was 30 mg/mL,the pH value of CS was 3.5,and the 5-ASA concentration was 100 mg/mL,the highest encapsulation of 5-ASA in the microcapsules was 82.3%,the drug loading capcity was 495.5 μg/mg,and the average particle size was 1.78 ± 0.02 mm.The characterization of FT-IR,SEM and XRD results showed that the polyelectrolyte composite CKGM/CS/TPP microcapsules was formed through the interaction between ions of CKGM,TPP and CS.It showed a capsule/nuclear-bilayer membrane structure with a tight internal structure,and 5-ASA is successfully loaded in microcapsules in the form of crystals.The swelling tests and in vitro drug release studies showed that the CKGM/CS/TPP/5-ASA microcapsules can be degraded by β-mannanase.5-ASA can be continuously released in simulated colon fluid(SCF,pH 7.0)and phosphate buffered saline(PBS,pH 7.0)for 8 h,and the release rate in the SCF was faster than that in the PBS.5-ASA in the microcapsules diffuses out in an irregular manner.The results indicate that CKGM/CS/TPP microcapsules may serve as a potential oral colon targeting drug delivery carrier.