Formulation of liposomes for protective functions for the human dental enamel
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AbstractThe present work concerns the development of liposomal formulations that can adsorb to the human dental enamel. The overall aim of this pharmaceutical approach is to physically protect the teeth against detrimental processes, such as tooth wear, acidic challenges and dental caries. Adsorption experiments of different liposomal formulations to hydroxyapatite (HA), a model substance for the dental hard tissue, and the human dental enamel were performed. To find which liposomal formulations are promising for the adsorption to teeth, formulation factors important for the interaction were initially mapped by the use of experimental design and multivariate analysis (Paper I). The type of surface charge became the most significant factor for the adsorption process. Positively charged liposomes adsorbed better than the negatively charged liposomes to HA in phosphate buffer, pH 6.8-7. However, the adsorption of positively charged liposomes to HA in a salivary environment was interfered as they were found to aggregate with components of saliva (Paper II). To overcome problems related to the positively charged liposomes, the surface of the liposomes was modified with the polymer pectin. Three types of pectin were investigated for the surface coating of liposomes: LM-, HM- and amidated pectin (Paper III). Pectin coating of positively charged liposomes was successfully prepared, and a reproducible method was established. Pectin coated liposomes did not seem to interact with salivary components (Paper IV), and were therefore promising for use in the oral cavity. Pectin coated liposomes adsorbed to HA in saliva, and liposomes coated with LMand HM-pectin were selected for further investigation with the dental enamel (Paper IV). Both uncoated negatively charged liposomes and pectin coated liposomes adsorbed onto enamel specimens in a salivary environment (Paper IV), indicating their potential use in the protection of the teeth. The adsorption was examined by exposing a flow on the enamel surfaces for certain time intervals. Pectin coated liposomes seemed to retain better than uncoated negatively charged liposomes at longer time intervals. It was hypothesized that pectin may help to prolong the adhesion of liposomes on the tooth surfaces.
List of papers
|Paper I Nguyen S, Solheim L, Bye R, Rykke M, Hiorth M, Smistad G The influence of liposomal formulation factors on the interactions between liposomes and hydroxyapatite. Colloids and Surfaces B: Biointerfaces 76 (2010) 354-361 The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1016/j.colsurfb.2009.11.020|
|Paper II Nguyen S, Hiorth M, Rykke M, Smistad G The potential of liposomes as dental drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics 77 (2011) 75-83 The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1016/j.ejpb.2010.09.010|
|Paper III Nguyen S, Alund SJ, Hiorth M, Kjøniksen AL, Smistad G Studies on pectin coating of liposomes for drug delivery Colloids and Surfaces B: Biointerfaces 88 (2011) 664-673 The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1016/j.colsurfb.2011.07.058|
|Paper IV Nguyen S, Hiorth M, Rykke M, Smistad G Adhesion of liposomes to the enamel surface for potential protective functions Submitted, not yet published. The paper is removed from the thesis in DUO due to publisher restrictions.|