Liposomes with improved drug retention for treatment of cancer

A - Human Necessities – 61 – K

Patent

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Details

A61K 47/02 (2006.01) A61K 9/127 (2006.01) A61K 31/4745 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2582949

The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

La présente invention concerne l'utilisation d'ions de cuivre pour mieux retenir un agent thérapeutique dans un liposome. L'invention peut être utilisée pour administrer plus efficacement un agent thérapeutique encapsulé dans un liposome vers un site cible in vitro et in vivo dans une thérapie anticancéreuse ou analogue. Le liposome peut contenir une solution tampon renfermant un agent thérapeutique, la solution ayant un pH inférieur à 6,5 et de préférence proche de 3,5. Au moins une partie des ions de cuivre sont retenus dans ladite solution. Dans un mode de réalisation particulier, l'agent thérapeutique peut être un produit chimiothérapeutique, tel que de l'irinotecan. L'invention peut également comprendre l'utilisation d'un ionophore pour faciliter l'introduction du médicament dans le liposome. Dans un mode de réalisation particulier, la combinaison du ionophore A23187 et du cuivre divalent encapsulé (Cu2+) permet d'obtenir une préparation d'irinotecan présentant des caractéristiques de rétention du médicament étonnamment supérieures.

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