engleski

Improved trapping efficiency of hydrophilic compounds into liposomes prepared by polyol dilution method

The goal of this study was to find an optimal preparation method for liposomes containing hydrophilic drugs. Since a majority of classical drugs are of low molecular weight, calcein (Mr 622.5) was chosen as a model compound. In order to find optimal conditions with regards to trapping efficiency of liposomes, different liposome preparation methods were used: film, detergent dialysis, high pressure homogenization, proliposome and polyol dilution. On all pre-formed liposomes a freeze-thaw procedure (five cycles) was applied. Prior to their characterisation, all liposomal preparations (before and after freeze-thawing) were extruded once through 400 nm polycarbonate membrane filters. As lipid membrane components egg phosphatidylcholine and egg phosphatidylglycerol-sodium in the molar ratio 9:1 were used. Total lipid amount of 12.8 mM and calcein concentration (200 µM) were kept constant in all preparations. Liposomes prepared by proliposome, polyol dilution and conventional film method were of similar mean diameter (between 280 and 300 nm). They were bigger than those prepared by detergent removal (70 nm) and high-pressure homogenisation (155 nm). Despite the evidence that larger multilamellar vesicles often entrap a lower amount of hydrophilic substance than smaller large unilamellar vesicles, the highest tapping efficiency was obtained for liposomes prepared by polyol dilution method (63%). Even after freeze-thawing procedure was applied to improve trapping efficiency, only 10% of calcein was trapped in liposomes prepared by other conventional methods. The results of our study have confirmed the polyol dilution method as a valuable technique for production liposomes in the laboratory conditions and for possible scalling up. The method is easy and produces liposomes which are stable over longer period of time.

Liposomes; Entrapment; Hydrophilic; Preparation methods

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