Preparation Of Albemdazole Solid Dispersions-chitosan Microspheres And Albendazole Chitosan Nanoparticles

Objective: In this paper, Preparation of albendazole solid dispersions-chitosanmicrospheres and albendazole chitosan nanoparticles were studied by usingChitosan(CS)as carriers and albendazole(ABZ) as model medicine. In-Vivo ImagingSystem was applied to investigate targeting of hepatic with two groups of nude miceexposed in fluorescence and X-ray. The main purpose of this paper was to developsustained-microsphere and a new formultion albendazole-loaded nanoparticles,investigate on the physico-chemical characteristics and pharmacokinetics to enhanceintestinal absorption and improve hepatic targeting in rats, aim to provide scientificbasis for the further research and clinical.Mthhods:(1)Microspheres were prepared by emulsion cross-linking techniquewith the orthogonal design was applied to optimize the technology of preparation; X-raydiffraction and Fourier infrared chromatography were used to analyza their structuralcharacteristics; Dynamic dialysis system was adopted to study the drug release frommicrospheres in vitro.(2)Albendazole-associated chitosan nanoparticles (ABZ-CS-NPs)were prepared by emulsion crosslinking–volatile technique and studied for entrapmentefficiency by HPLC; In vitro drug release study were also studied and kineticmodellings were employed to find out the mechanisms; The cryoprotectants of2%,3%and5%sucrose, lactose, mannitol were studied in freeze-drying test in order to evaluatethe protection of nanoparticles and choose the best cryoprotectant.(3)The targetingabilities of the ABZ-CS-NPs was demonstrated using a near-infrared (NIR) fluorescenceimaging system with cy7-CS as contrast group. The NIR fluorescence signals weremonitored at scheduled points after oral administration of the NPS and cy7-CS in nudemice, respectively.(4)The liquid-liquid extraction method was applied in biologicalsamples extraction with mebendazole (MBZ) as internal standard. Then, RP-HPLCmethod was established to determine the concentration of ABZ and ABZSX in bloodsamples. Pharmacokinetics parameters were calculated by3P97program.(5)Set up an animal model,80liver lesions rats were divided into four grous to observe thepathological and histological change.Results:(1)The loading drug content and encapsulated efficiency ofmicrospheres were (6.42±0.32)%and (37.86±0.74)%; Microspheres were sphere,uniform and less of adhere with average diameter was (210±8)μm and60%of the allmicrospheres in100-300μm; Reaction between chitosan and glutaraldehyde wereanalysised with FT-IR and X-ray, indicating ABZ-PEG6000was dispersed in chitosanmatrix; The release behavior of ABZ-PEG6000-MS in medium followed Higuchi model.(2) ABZ-CS-NPs showed non aggregated and spherical characteristics with averageparticle size was (157.82.82) nm in diameter and the loading drug content andencapsulated efficiency were (13.380.44)%and (79.570.96)%; the release behaviorfound to be affected by pH level in solution, and the rate of drug release followedHiguchi model.(3)After overlaying the x-ray and fluorescence image, cy7-cs weregradually distributied and were diffused during the48h post-administration. Meanwhile,Nps gradually concentrated to the liver besides the normal hepatic metabolism.(4)Theplasma concentration versus time curve was coincident with two compartment model;Compared with abz-suspension, the relative bioavailability of ABZ and ABZSX were146.05%and222.15%. and AUC, tmax, T1/2of NPs was higher than that ofABZ-suspension (P0.05).(5)Compared with the model group, three ways ofadministration all had good treatment effect, notably, the treatment of nanoparticles inPortal venous infusion had best resistance to echinococcosis.Conclusions: The optimized technology presented good stability and excellentrepeatility and the pH sensitivity and sustained drug release characteristic ofABZ-CS-NPs were revealed. CS-based nanoparticles exhibit the potential of widelydistributed and low bioavailability to comprise a safe liver-targeting delivery system,and the ensuing accumulation of ABZ and ABZSX in the liver showed the prospectiveof the albendazole-loaded nanoparticles with hepatic targeting for the treatment ofhydatid cysts effectively in the future.