The analgesic effect of liposomal formulations of a local anesthetic and narcotic could be enhanced by their combined encapsulation. We approach the development of the combined liposomal encapsulation of bupivacaine and morphine by assessing with conformational analysis techniques their stability in the lipid bilayers. We synthesize multilamellar phospholipid vesicles for encapsulation of bupivacaine and morphine based on these theoretical data and at different concentrations of each drug in the phospholipid bilayers of the same liposome. Both compounds will be included as apolar molecules or as cations in the preliposomal lipid film. The encapsulation efficiency of morphine and bupivacaine are confirmed by HPLC. We study the release of the two drugs entrapped in a closed system at pshysiological pH to determine if both drugs are able to leak out of the liposomes following a gradient of concentration, and to measure the time needed for drugs clearence from an intraliposomal medium. We select the formulation with an appropriate slow release in vitro corresponding to clinical needs and perform the necessary quality controls for integrety, structure, sizing and oxidation of the liposomes. We study the pharmacokinetics of such vesicles in animals following their epidural administration and establish the interaction profile of the release of the two drugs for their pharmacodynamic analgesic effects.
Effective start/end date1/01/9831/12/01

    Research areas

  • medicine, pharmacology

    Flemish discipline codes

  • Basic sciences

ID: 2926248