Fabrication Of Pulsatile Delivery Device Based On Liesegang Periodic Pattern

The periodic and concentric Liesegang rings(LRs)of CaHPO4 were engineered by employing CaCl2 and Na2HPO4 as the inner and outer electrolyte,respectively,in the new medium of gelatin mixed with the surfactant,sodium dodecyl benzene sulfonate(SDBS).Utilizing the obstacle of precipitated crystals in ring layer to the enzymolysis of gelatin and capsulation of water-insoluble drugs with SDBS,it was anticipated to fabricate a multi-pulsed drug delivery device by LRs.Oil-soluble cholesterol was selected as the model drug.Various factors possibly affecting the formation of LRs under the existence of SDBS were investigated,evaluating with the ring numbers,distance of adjacent rings and ring width.As a result,two critical initial concentrations of SDBS were observed.[SDBS]0<10 mM,the effect of SDBS was insignificant to the formation of LRs.16 mM>[SDBS]0>10 mM,the effect of SDBS was serious.The number of rings increased and the ring width decreased as[SDBS]0 increased.However,the distance of adjacent rings changed insignificantly.As we know,the spacing law of LRs formation in the absence of surfactant tells that the distance of adjacent rings increases as the ring number increases.Hence,the results obtained in the presence of SDBS indicated that it did not obey the normal spacing law.At[SDBS]0=15 mM,the isometric LRs formed.However,[SDBS]0>18 mM,the whole gelatin became white as the reaction of CaCl2 and Na2HPO4 progressed.It implies that the rings with the infinite short distance of adjacent rings formed.Since SDBS interacted with gelatin molecules,the mechanism was unclear so far.However,it was clear that the concentrations applied to prepare the isometric LRs were much higher than the critical micellization concentration(CMC)of SDBS(1.2 mM).It indicated that most of SDBS in gelatin should exist in form of micelles.Moreover,pH of gelatin solution greatly impacted on the morphologies of LRs.When pH<3.4 or>8,the gelatin could not be gelated,thus LRs was just formable at the pHs ranging from 3.4 to 8.As pH decreased,the number of rings increased,and the ring width decreased.It indicated that the acidic condition benefited the formation of LRs.Under the acidic condition,H+ interacted with amino groups on the gelatin chains,replacing Ca2+.Hence,the diffusion of Ca2+ was relieved.At meanwhile,the high concentration of H+ increased the critical concentration of CaHPO4 deposition,thus the number of rings increased,but the distance of adjacent rings decreased as pH increased.On the basis of above results,replacing SDBS with the nano-capsules of SDBS/cholesterol,the isometric LRs was prepared and applied for the enzymolysis.The results indicated that the rings consisted of CaHPO4 crystals were applicable to be used as blocks to the enzymolysis of gelatin in LRs.