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Non-viral vectors are a safe, efficient and non-toxic alternative to viral vectors for gene therapy against many diseases ranging from genetic disorders to cancers. Polyamidoamine (PAMAM), a positively charged dendrimer has a tendency to complex with nucleic acids (to form dendriplexes) like plasmid DNA (pDNA) and small interfering RNA (siRNA) and can shield them from enzymatic degradation, thereby facilitating endocytosis and endosomal release. In this study, we developed an advanced variant of the dendriplexes by encapsulating them within liposomes to enhance their gene delivery efficiency. This liposome encapsulated dendriplex system can further reduce unwanted cytotoxicity and enhance cellular uptake of nucleic acids. A broad range of lipid combinations were used to optimize the lipodendriplexes in terms of their physicochemical characteristics including size, shape and zeta potential. The …