Salidroside-loaded IPN Microspheres Of CS And MC:Preparation,Characterization And In-vitro Release Evaluation

Salidroside,a medicinal and edible natural substance with diverse health and pharmacological activities,is becoming a research hotspot in pharmaceutical,food and health industry.Presently,kinds of functional food products containing salidroside have been developed,but none of them could avoid problems like the subsequent fluctuations in blood concentration,poor sustained-release effect,requirement of high intake frequency,all of which lead to the low bioavailability of salidroside and limit its application in pharmaceutical and food area to some extent.Interpenetrating polymer network(IPN)is a concept derived from materials field.It provides a method for the blending modification of polymer materials and can integrate their advantageous properties,combined with its excellent swelling,mechanical and thermodynamic properties,it has been used in drug delivery applications in recent years.This research attempts to build IPN microspheres composed of two biodegradable materials-chitosan(CS)and methyl cellulose(MC)for the encapsulation of salidroside,in order to improve its stability,achieve controlled and sustained-release effect,and improve its bioavailability.Firstly,a synchronized emulsion chemical cross-linking method was employed in the preparation of placebo CS-MC IPN microspheres,the influences of six major factors on the spherical property,dispersity,particle size and swelling degree of IPN microspheres were investigated.Under the optimized conditions:reaction time for 3 h,stirring speed at 500 rpm,oil-water ratio of 5:1,3 mL of crosslinker,2 mL of emulsifier,material concentration ratio of 4:1,highly spherical microspheres with smooth surface,good dispersity and particle size from 10 to 20?m were obtained.The detection wavelength of salidroside was determined as 275 nm by UV scanning spectrum,the standard curve equation was A=5.3467C+0.0086,R2=0.9996,method recovery reached 99.78%.Salidroside-loaded IPN microspheres were successfully prepared,the impact of initial addition of salidroside on encapsulation efficiency(EE)and particle size was examined,results showed that both of EE and particle size increased with the increase of initial addition.Microspheres were characterized by following method:FT-IR was used to conform the formation of IPN structure and chemical stability of salidroside;DSC and X-RD to analyze the compatibility of materials and existing form of salidroside in microspheres;SEM to observe the surface morphology and internal structure of microspheres;results were as follows:crosslinked reaction took place between CS,MC and glutaraldehyde to form IPN structure;chemical stability of salidroside was fine;CS and MC had blended evenly,salidroside was dispersed molecularly or amorphously in microspheres;salidroside-loaded microspheres were spherical with pleated surface,thick wall,and hollow structure,their mean particle size was slightly larger than the placebo microspheres.Salidroside-loaded CS microspheres were prepared and compared with IPN microspheres on EE and particle size,mean particle size of IPN microspheres was larger than CS microspheres while EE was a little lower.In-vitro release of the two kinds of microspheres were performed to study and compare their release characteristics,results indicated that IPN structure contributed to a reduction of initial burst release,extending release time,thus achieved better sustained-release effect.The effect of different release medias on release of salidroside-loaded IPN microspheres was investigated.The amount of burst release and early release rate in simulated gastric fluid(SGF)was higher than that in the other two medias,but there was a lag period after 12 h.Release in simulated intestinal fluid(SIF)was similar to that in phosphate buffer solution(PBS),both of which showed preferable sustained-release effect.The release results of microspheres were fitted using several common mathematical models,the first order model and Higuchi model showed good fitting efficiency,Higuchi model was relatively satisfactory.The fitting results of Peppas model together with Higuchi model gave an evidence that the release of salidroside microspheres follow Fickian diffusion mechanism.Weibull probability distribution model fitted the release data very well,goodness of fit exceeded 0.99.The release mechanism of salidroside-loaded IPN microspheres was discussed combined with the fitting results.The initial stage of release was salidroside dissolved from the surface,followed by a stable diffusion release stage,salidroside diffused from swollen polymer network or porous structures in this stage,within time extended,release was mainly affected by erosion of microspheres,thus release rate slowed gradually,which suggested that IPN microspheres are effective sustained-release carrier.