Study On The Novel PH-Sensitive And Sustainable Drug Delivery System

Mesoporous silica materials are known as ideal drug supports due to their high pore volume and high surface area, good biocompatibilities, non toxicity and pharmacological activity. Mesoporous silica materials facilitate the adsorption of high pharmaceutical drug amount whether the drug is hydrophilic or poorly soluble drug, and mesoporous materials can achieve sustained/controlled drug delivery. The human body is a complex environmental system, and exhibits variations in pH in different parts, pH-sensitive drug delivery system is important for human. Alginate/chitosan hydrogels (AC hydrogels) is pH-sensitive, which can achieve pH-sensitive controlled drug delivery.This paper proposed a strategy to combine mesoporous silica and AC hydrogel together to prepare a novel pH-sensitive and sustainable drug delivery system-AC gel beads doped by different mesoporous silica (AC/MPS gel beads) for pH-sensitive sustainable drug release system, this system not only overcome the shortcoming of the two types of materials, but also have special characteristic, and the preparation is simple and convenient. we have mainly studied the contents as follows:1. In this paper, mesoporous silica MCM-41 and SBA-15, which have different pore size: the pore size of MCM-41 and SBA-15 is 3.6nm and 9.8nm respectively, were synthesized and functionalized by amine group via post-grafting synthesis. Indomethacin(IDM), a poorly soluble drug, as the model drug. The mesoporous silica materials were used as a carrier for IDM. The loading of IDM in mesoporous materials was studied.2. The release performance of IDM loaded in mesoporous materials in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) were studied. The results suggested that IDM loaded mesoporous silicas showed a sharp initial burst; the release rate of the drug from MCM-41 with small pore size was slower than that from SBA-15 with large pore size; the release rate of the drug from amine-functionalized mesoporous materials was slow in comparison with that from unfunctionalized mesoporous materials; Because of the electrostatic repulsion in SIF and hydrogen bonds in SGF between mesoporous materials, so the release speed of IDM in SGF was slightly slower than that in SIF.3. The encapsulation efficiency of AC/MPS gel beads were higher than that of AC gel beads, and the addition of mesoporous silica didn't affect the swelling rate of AC gel beads. The release performance of IDM loaded in AC/MPS gel beads in SIF and SGF suggested that the release of drug showed significant pH-dependence, In SIF, the release rate of IDM was fast, and in SGF, the release rate was slow. The release speed of drug loaded in AC/MPS gel beads was slower than that in AC gel beads. The initial burst of the AC/MSP gel beads was reduced significantly in comparison with that of the mesoporous silica.4. The release mechanism of IDM was studied. The results suggested that the data of release kinetics in SIF and SGF from mesoporous silica can be well fitted by the classic Higuchi model, the mechanism of drug release was a diffusion-controlled process. The data of release kinetics from the AC/MPS gel beads can be well fitted by the classic Higuchi model in SGF, Ritger-peppas model in SIF. The mechanism of drug release in SIF was non-Fickian diffusion-controlled process, that is, the drug diffusion was main process, and skeleton corrosion synergy.The AC/MPS gel beads system have achieved pH-controlled drug release successfully in the gastro-intestinal tract. This gel beads can overcome the shortcoming of seriously gastric irritation and side effects of some drug taken orally, protect the drug from absorption by the stomach or break by the enzyme present in the stomach, and prolong therapeutic efficiency, enhance drug stability. Furthermore, the preparation of this gel beads is simple, time-saving and economical. We believe that this new pH-sensitive sustainable drug release system used for sustainable drug release in intestinal tract have big potential.