Modulation of Drug Release from Polymeric Carriers and Systems

Controlled drug delivery systems, which are intended to deliver drugs at predetermined rates for predefined periods of time, have been used to overcome the shortcomings of conventional drug formulations. Injectable drug-loaded matrices and controlled release technology offer numerous advantages compared to conventional dosage. However, one of the greatest challenges in applying this system to the clinical phase is the relatively large initial burst release. To reduce this effect of large initial burst release, a new drug delivery system was fabricated in this thesis. Both alginate and gelatin are biocompatible nature polymers and have been largely used as biomaterials for long time. By cross-linking alginate solution carrying drug-loaded uncross-linked gelatin microbeads, the initial burst release was reduced significantly, compared with drug directly releasing from gelatin or cross-linked alginate matrix. Firstly, a series of gelatin microbeads were prepared in a water-in-oil (W/O) emulsion by a traditional emulsification method. The effects of the concentration of gelatin solution, volumetric ratio of water-to-oil phase, stirring speed and emulsifying time on the particle size and dispersity of gelatin microbeads were studied. Secondly, drug-loaded gelatin microbeads were encapsulated into the cross-linked sodium alginate macro-beads. The release behavior of drug-loaded gelatin microbeads encapsulated within cross-linked alginate gel was characterized both at room temperature and 37°C and compared with the release from gelatin microbeads and cross-linked alginate gel alone. This system represents a promise for the development of novel and versatile injectable drug delivery systems. Thirdly, a dual-drug delivery system was fabricated by encapsulating drug-loaded gelatin microbeads into the mixture of cross-linkable sodium alginate and another drug. The effects of preparation methods of drug-loaded gelatin microbeads and ratio between gelatin microbeads and alginate on drug release behaviors of both drugs were studied. This system shows a significant potential in dual drug delivery field due to the synergistic effect between gelatin and alginate. Additionally, combination of multi-drugs in one system has been revealed as a promising application in the drug delivery systems. Therefore, in the fifth chapter of this thesis, an idea for the multi-drug delivery system was simply demonstrated. Rods of gelatin gels loaded with different drugs were separated by the agarose gel in a polycarbonate tube. The effects of the length of agarose gel and temperature on the drug release profiles were investigated. The results suggested the feasibility to employ this idea to the practical applications.