| Summary: | 碩士 === 國立宜蘭大學 === 生物技術研究所碩士班 === 97 === Since the injection administration as the peptides and proteins delivery system, it imposes discomfort and inconvenience on patients, particularly for a long-term treatment. Therefore, the goal of this thesis is to find out an oral delivery system for improving the absorption of therapeutic protein drugs.
Emulsion is one of strategies known delivery vehicles for those oral medicines. Water-in-oil -in-water (W/O/W) multiple emulsion has been known to be possible to protect protein drugs from enzyme degradation and enhance the absorption of hydrophilic drugs to systemic circulation. Therefore, we tried to use granulocyte colony-stimulating factor (G-CSF) as the indicator to test the emulsion formulation for the oral delivery system in the study.
In this two-step emulsification procedure, the data of the droplet size (2 μm of diameter), encapsulation efficiency (40±5%), stability (at pH 1.2 for 2 hrs and 60°C for 5 days), permeability (into Caco-2 cell monolayer with 30 min) and in vitro cytotoxicity studies all showed that the emulsion formulation was indicated to promote the absorption of proteins drugs by oral administration. Thus, we used the E. coli expression system to express and purify the recombinant human G-CSF (rhG-CSF). And then, rhG-CSF was incorporated into the inner aqueous phase of the emulsion for the test of oral bioavailability. After 6 hrs of oral administration of various dosages of rhG-CSF in solution or in emulsion for 7 days, the proliferations of leukocytes in the two treatments with the highest dose of rhG-CSF (2,500 μg/kg/day) were significantly higher than the blank emulsion (p < 0.01). However, two of them, rhG-CSF in emulsion and not in emulsion, were not different. After 12 hrs of oral administration, mice, administrated by 50, 500, and 2500 μg/kg/day rhG-CSF emulsion, all presented a significant elevation in leukocyte numbers when compared to the blank emulsion (p < 0.01). Finally, it was indicated about the advantages of the W/O/W multiple emulsions with encapsulation efficiency, penetrating ability, and stability to resist acid pH (1.2) and high temperature (60°C). In the future, it could be potential for protein drugs delivery by oral administration.
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