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Drug Delivery Systems Based On Nano-cellulose And Liposome

Posted on:2014-11-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:L HuangFull Text:PDF
GTID:1221330425473297Subject:Biopharmaceutical works
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Bacterial cellulose (BC) is natural, easy to get, non-toxic and has a nanoscale network structure, which has the great potential applications for novel drug carriers. Liposome, as a mature drug carrier, has cell-like structure, targeting property, reducing drug side effects and other advantages. In this paper, we chose BC membrane, liposome and the BC-liposome complex as drug delivery, berberine hydrochloride and berberine sulfate with good effect on heart disease, diabetes and cancer but low bioavailability as the model drug to prepare the drug delivery systems with the properties of controlled release and good bioavailability.The naturally hyperfine nano-network structure of BC gives its sustained-release property as the novel drug carrier. The Prepared methods were screened, and freeze-dried BC membranes with the thickness of10mm were found the optimal for drug delivery. Compared to commercially available tablets, BC can significantly prolong the drug release time. Scanning electron microscopy (SEM) analysis demonstrated that the acid and alkali influenced the release behavior by swelling the BC fibers. The release curves closely followed the Ritger-Peppas model with free diffusion as the most prominent mechanism. The interaction mechanism between drug and carrier was discussed deeply.’H high-resolution magic angle spinning nuclear magnetic resonance (1H HRMAS NMR) diffusion-ordered spectroscopy (DOSY) analysis showed that hydrophobic interactions existed between BC and drug. The biocompatibility, size bio-controllability, high mechanical strength and physicochemical stability of BC makes it can be developed as a promising oral drug carrier.The drug-loaded liposomes were prepared by the thin-film evaporation and active drug-loaded method. The average size of blank liposome particle was about80nm, and after loading drug, the particle sizes were increased to110-160nm. All PDI were below0.2, which means the narrow size distributions. Liposomes were substantially electrically neutral. The encapsulation efficiency of drug was high, more than80%. The morphologies of liposomes were observed by transmission electron microscopy (TEM). They were spherical with the core-shell structure.The sustained release of drug-loaded liposomes exhibited a pH response property. The release curves closely followed the Ritger-Peppas model with both the drug free diffusion and skeleton dissolution as the most prominent mechanisms. Animal experiments demonstrated that the peak concentration of berberine (Cmax) and area under concentration-time curve (A UC) of liposome-berberine were significantly increased compared to berberine solution. Therefore, the preparation methods of liposomes were good, which can achieve the dual purpose of improving release behaviors and bioavailability of drug.In order to enhance the stability of liposomes, BC with high mechanical strength was added. Three different methods were used to synthesize BC and liposome composite, and in situ synthesis method was the best. This complex combines the advantages of BC and liposomes, with the dual advantages of cell affinity and high stability. Moreover, this complex can achieve the purposes of reducing drug release in stomach and increasing drug release in small intestine.BC as a novel oral drug carrier material, shows good performance of sustained-release, and has pH-responsive property. Liposome-based drug carrier, not only has sustained effects, but also can significantly increase the berberine absorption into the blood. The complex combined their respective strengths and started exploring the new carrier which is strong and stable, possesses sustained release capacity and can improve bioavailability of drug.
Keywords/Search Tags:Sustained-release, Bacterial cellulose, Liposome, Berberine hydrochloride, Berberine sulphate
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