Formulation and characterization of a stable vinorelbine-PAMAM conjugate loaded liposomes

The cancer activity of vinorelbine is primarily due to inhibition of mitosis during metaphase of cell division process and its interaction with tubulin. The aqueous solubility of the vinorelbine is > 1000 mg/mL in distilled water. Prolonged vinorelbine exposure is resulted in improved antineoplastic effects, as evident by improved response rate during patients receiving a continuous infusion of the drug. A phase-I pharmacokinetic study of the vinorelbine liposomal injection has been reported and concluded well tolerated and exhibited more favourable pharmacokinetic profiles than free vinorelbine. Dendrimers are new class of artificial macromolecules. Dendrimer possess a well-defined topological structure, are versatile candidates as scaffolds or vehicles for nanomedicine the field of cancer diagnosis and therapy. Dendrimers can be used for conjugating of anticancer compounds and by non-covalent interactions (ionic, hydrophobic, hydrogen-bond interactions) and spacer-mediated conjugates. Also, they can be used for targeting to cancer cells, tumour tissues or abnormal vessels adjacent to the disease focus based on the molecular ‘‘hooks’’ conjugated on the surface of dendrimer through active targeting, and can be accumulated in tumours via the enhanced permeability and retention (EPR) effect of the nanosized dendrimer through passive targeting effect of the nanosized dendrimer through passive targeting. Targeting to tumour tissues & prolonged release profile can further improved by encapsulating vinorelbine-PAMAM conjugated inside liposome. In this study we formulated and characterized a stable vinorelbine-PAMAM conjugate liposomal formulation.