Preparation and evaluation of alginate-pectin-poly-l-lysine particulates for drug delivery and evaluation of melittin as a novel absorption enhancer

Liu, Ping (1998) Preparation and evaluation of alginate-pectin-poly-l-lysine particulates for drug delivery and evaluation of melittin as a novel absorption enhancer. Masters thesis, Memorial University of Newfoundland.

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Abstract

I -- Drug delivery particulates were prepared using alginate (ALG), poly-l-lysine (PLL) and pectin (PEC). Theophylline, chlorothiazide and indomethacin were used as the model drugs for in vitro dissolution, and mannitol was used as the model for assessing paracellular drug absorption across Caco-2 cell monolayers. ALG and PEC served as the core polymers; PLL helped to strengthen the particulate and PEC also helped to modulate the release profiles of the encapsulated model drugs. In vitro dissolution tests of ALG-PEC-PLL in acidic and alkaline media showed sustained drug release of the model drugs. In vitro bioadhesive tests indicated that the particulates had good bioadhesive properties. ALG and PEC also enhanced paracellular absorption of mannitol across Caco-2 monolayers by about three times. Use of ALG-PEC-PLL particulates is expected to combine the advantages of bioadhesion, absorption enhancement, and sustained release. This particulate system may have potential use as a carrier for poorly absorbed drugs by the oral route of administration. -- II -- In this study, the possibility of using melittin as a novel absorption enhancer was investigated. The membrane fusion peptide, melittin, is the major active ingredient of honey bee venom. Its action as a membrane fusion peptide on membrane has a strong concentration dependency. By incorporating melittin, which is itself a peptide, along with the drug in a particulate system, such as ALG-PEC-PLL particulates, we anticipate that a sufficient quantity of the drug and the enhancer will be delivered at the absorption site. Caco-2 cell line was used as the model cell line and mannitol was used as the model drug for transport study. MTT assay was performed to evaluate the cytotoxicity of melittin. The results indicated that at a concentration below 2.42 μM melittin did not show any cytotoxic effects on Caco-2 cells. Transport study showed that 1.20 - 1.50 μM of melittin was able to increase the absorption of mannitol across Caco-2 cell monolayer by a factor of 3.5. -- Linking part I and II of the project -- The particulate system developed in part lf could be used to carry a drug and melittin (as an enhancer). It is envisaged that the pectin-alginate-poly lysine particulate will protect melittin (a peptide compound) in a biological environment that is 'hostile' to peptide molecules, thus enabling melittin to exercise its action as an absorption enhancer. This is an ongoing project and further work will be done in our laboratory.

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