Study On Preparation And Release Of Bilayered Chitosan Particles With Short-term Storage Stability And Colon Targeting

With the improvement of living standards,functional foods have received extensive attention.How to improve and balance the storage stability and bioavailability of the functional factors is an important issue in the research and development of functional food.Functional factors that have special physiological functions need carrier material to protect them,to avoid the function factors being eroded by acid and enzyme in the upper digestive tract of the human body,transfer them to the colon,and improve their bioavailability by the special physiological environment of the colon.Therefore,we selected cross-linked chitosan with slight differences in properties and structure was used to prepare double-layered cross-linked chitosan particles.With the help of internal and external carrier materials,the problems caused by changes in environmental conditions during storage and digestion were successively solved,and the short-term storage stability and bioavailability of functional factors were improved.In this paper,chitosan with different molecular weights was modified with sodium tripolyphosphate(STPP)and sodium hexametaphosphate(SHMP),and bovine serum albumin(BSA)was used as a model functional factor to prepare cross-linked chitosan particle.The effects of pH of acetic acid-sodium acetate buffer,the mass ratio of chitosan and crosslinker,the concentration of crosslinker and BSA,and the preparation time on the BSA entrapment rate of crosslinked chitosan particles were investigated.At the same time,the average particle size,Zeta potential,surface morphology,aggregation structure,and changes in storage and digestion properties of cross-linked chitosan particles with different structures were studied.The experimental results showed that the cross-linked chitosan particles can basically achieve controlled release of functional factors in the colon(the STPP cross-linked medium viscosity chitosan(M-STPP)was not released in the upper gastrointestinal tract and its release rate in the colonic environment was 30.69%),and the tighter the internal ordered aggregate structure of the cross-linked chitosan particles(analysis dimension of STPP cross-linked low-viscosity chitosan(L-STPP),M-STPP,SHMP cross-linked low-viscosity chitosan(L-SHMP)and SHMP cross-linked medium-viscosity chitosan(M-SHMP)were 1.253,1.329,1.551 and 1.985,respectively),the better the storage property of BSA(compared with the above tightness,the maximum leakage rates of L-STPP,M-STPP,L-SHMP,and M-SHMP for 30 days were 82.96%,65.08%,63.92%,and 45.85%,respectively).The leak rate of BSA in PBS buffer increased with the lengthening of storage time,and then affected the colonic release of functional factors(among them,the leakage rate of L-STPP stored for one day was 28.49%,and the leak rate for storage 30 days was 78.08%).And it is difficult to achieve both the storage stability and the targeted colonic delivery of the active functional factors by only relying on a single layer of carrier material.On the basis of single-layer cross-linked chitosan particles,6 kinds of bilayer-crosslinked chitosan particles,such as STPP cross-linked low-viscosity chitosan/SHMP cross-linked low-viscosity chitosan(L-STPP/L-SHMP)?STPP cross-linked medium-viscosity chitosan/SHMP cross-linked low-viscosity chitosan(M-STPP/L-SHMP)?STPP cross-linked low-viscosity chitosan/SHMP cross-linked medium-viscosity chitosan(L-STPP/M-SHMP)?STPP cross-linked medium-viscosity chitosan/SHMP cross-linked medium-viscosity chitosan(M-STPP/M-SHMP)? SHMP cross-linked low-viscosity chitosan/STPP cross-linked low-viscosity chitosan(L-SHMP/L-STPP)and SHMP cross-linked medium-viscosity chitosan/STPP cross-linked low-viscosity chitosan(M-SHMP/L-STPP),were constructed.Through Attenuated Total internal Reflectance Fourier Transform Infrared spectroscopy(ATR-FTIR),it was clear that the two layers of carrier material inside and outside are sequentially coated to form double-layer particles.Compared with chitosan particles,the leakage rate of BSA decreased during the short-term storage of bilayer-crosslinked chitosan particles in PBS buffer at different pH(the M-STPP in the monolayer is the most compact,with a minimum leakage rate of 46.47% and the M-SHMP/L-STPP in the double layer was the most compact,and the minimum leakage rate was 43.59%).After being stored in PBS buffer and then digested,double-crosslinked chitosan particles can also achieve colon-target controlled release of functional factors(L-STPP/L-SHMP did not release in the upper gastrointestinal tract and its release rate in colonic fluid was 43.44%).By means of the characterization of the average particle size,Zeta potential,morphology,and internal ordered aggregate structure of six bilayer cross-linked chitosan particles,the results showed that L-STPP/M-SHMP and L-SHMP/L-STPP double-layer cross-linked chitosan particles have good protective effect on functional factors during short-term storage.In neutral environment,the Zeta potential of particles was close to 0,and the structure of particles was stable.At the same time,according to the analysis of SAXS results,the change of the ordered aggregate structure inside the particles was mainly on the surface.It indicated that a relatively stable structure system helped the functional factors in particles to have both storage stability and colon targeted delivery.In this dissertation,the cross-linking modification of chitosan was used to obtain carrier materials suitable for the embedding of functional factors.The storage performance and the release regularity of simulated digestive tract from human body of single-layer/double-layered cross-linked chitosan particles were obtained.Combined with the structural information of single-layer/double-layer cross-linked chitosan particles,we had a preliminary grasp of its regulatory mechanism.The results of relevant research have made some explorations for solving the problems of consideration to both storage stability and bioavailability of functional factors in the functional food field.