Preparation and characterization of Vancomycin liposomes

Vankomicin je glikopeptidni antibiotik koji se koristi kod infekcija meticilin-rezistentnim Staphilococcom aureusom (MRSA). Vankomicin može uzrokovati nefrotokičnost u ovisnosti o primjenjenoj dozi, do 40% slučajeva. Primjena vankomicina u formulaciji s liposomom, sfernom lipidnom vezikulom, pokazuje smanjeno zadržavanje vankomicina u bubregu i stoga smanjenu nefrotoksičnost. Liposomi s vankomicinom pripravljeni su metodom hidratacije filma te metodom smrzavanja. Karakterizirani su koristeći optičku mikroskopiju, mikroskopiju atomskih sila (AFM), diferencijalnu skenirajuću kalorimetriju (DSC), dinamičko raspršenje svjetlosti (DLS) te elektokinetiku. Optičkom mikroskopijom dokazano je postojanje liposoma. DSC-om je pokazano kako metode priprave značajno utječu na termička svojstva liposoma. DLS-om je pokazano kako prazni liposomi imaju sličnu raspodjelu u veličini kao i liposomi s uklopljenim vankomicinom. ζ-potencijal praznih liposoma veći je od ζ-potencijala liposoma s uklopljenim vankomicinom što ukazuje na veću nestabilnost i sklonost agregacije liposoma s vankomicinom, što je potvrđeno i AFM-om. Enkapsulacijska efikasnost vankomicina najveća je u lipsomima pripravljenima metodom smrzavanja mjerena 30 dana nakon priprave.Vancomycin is a glicopeptide antibiotic used for treatment of infections caused by methicillin-resistent Staphylococcus aureus. Nephrotoxicity is observed in up to 40% of cases, depending on the dosis. In formulation with liposomes, lipid vesicles, vancomycin’s concentration in the kidney lowers faster, reducing the nephrotoxicity. Vancomycin liposomes were prepared using thin film hydratation and freeze-thaw method. Characterization was made by optical mycroscopy, atomic force microscopy (AFM), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and electrokinetics. Using optical microscopy, the existence of liposomes was proved. DSC results suggest that thermodynamic properties of liposomes significalntly depend of the preparation method. DLS showed that empty liposomes and vancomycin liposomes have almost the same size distribution. ζ-potential was greater for empty liposomes in comparison to vancomycin liposomes, suggesting that vancomycin lipsomes are less stable and more prone to aggregation, which was confirmed by AFM. Encapsulation efficiency of vancomycin was the highest in liposomes prepared by the freez-thaw method when the analysis was performed 30 days after preparation