Fat Soluble Vitamins in Liposomes: Studies on Incorporation Efficiency and Bile Salt Induced Vesicle Disintegration

AbstractA systematic investigation has been undertaken to study the possible role of liposomes in facilitating the absorption of fat soluble vitamins (FSV) after oral administration in situations where FSV absorption is impaired. Conditions for the optimal incorporation of vitamins A, D3 and E individually or in combination, into multilamellar liposomes composed of egg phosphatidylcholine, dipalmitoyl phosphatidylcholine or distearoyl phosphatidylcholine (total vitamin to phospholipid molar ratios of 0.5:1, 0.75:1 and 0.9:1) have been studied. When two or three FSVs were incorporated simultaneously, FSV molar ratios used were based on the daily allowances (RDA) recommended for human males by the US Food and Nutrition Board. [Monitoring of FSV incorporation was carried out by the assay of 3H radioactivity (vitamins D3 or E, incorporated either individually or together with vitamin A), fluorometrically (vitamin A) or by an HPLC method developed in the present study for the assay of all three FSV simultaneously.] Incorporation yield of FSV used alone or in combination was found to decrease with increasing total vitamin to phospholipid molar ratio and to broadly depend on the phospholipid used. Although a vitamin to phospholipid molar ratio of 0.5:1 was found optimal in terms of percent vitamin incorporation (up to about 94% of the amount used), greater absolute amounts of FSV were recovered in most of the formulations with higher molar ratios. Moreover, when two or three FSV were incorporated simultaneously, amounts recovered with liposomes were reasonably similar to the RDA used initially. Results from exposure of liposome formulations containing all three FSV to the biologically relevant sodium deoxycholate at 37°C, indicate that vesicle stability is greater for phospholipids with a high gel-liquid crystalline transition temperature and is enhanced by the presence of FSV.