Studies On Rapamycin-loaded PH-sensitive Nanoparticlulate Drug Delivery System For Oral Administration

Objective: Rapamycin, also know as Sirolimus, is belong to macrolides antibiotics. Rapamycin as an immunosuppressant drug and anti-cancer agent has good therapeutic effect and low renal toxicity. According to literatures, RAPA, well soluble in various organic solvents such as methanol and ethanol but poorly soluble in water, has poor oral absorption, and incomplete bioavailability. At present, the marketed formulation of RAPA is emulsion, which contains considerable quantities of surfactants and co-surfactants, which may cause mucosa damage of the gastrointestinal tract for frequent long-term use. This study was to prepare pH sensitive nanoparticles drug delivery system which consisting of the nanosized and micronsized silicon dioxides as carrier materials with coated by the Eudragit? polymer.Methods: Mono-factor analysis and Orthogonal experimental design were used to screen the optimum formulation and technology. In the condition of laboratory, the final optimum solid preparation was prepared and investigated, including in vitro release, scanning electron microscope(SEM), X-ray diffraction and FT-IR spectrum. The pharmacokinetics study of the final solid preparation of RAPA was performed after administered orally in normal SD rats.Result: The results of in vitro release experiments showed that the nanoparticulate drug delivery system has perfect pH dependant sensitivity, a little drug was released in mimic gastric fluid, but a large drug was released quickly in mimic intestinal fluid. It was shown from X-ray diffraction and FT-IR spectrum that there is no chemical reaction between drug and carriers. It suggested that drug molecule was evenly dispersed in the polymeric matrix of the solid preparation. The pharmacokinetics study reveals that the relative bioavailability and the oral absorption ability markedly increased to 266.05 %, respectively when compared with the RAPA microemulsion.Conclusion: In conclusions, the nanoparticulate solid preparation might be a potential carrier for improving the oral bioavailability of water insoluble drugs, with simple preparation technology and easy industrial production.