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There have been a few studies on the safety of cancer therapeutic drugs delivered by cationic lipids. However, most of these have been confined to intravenous administration and have concentrated on toxic effects due to massive killing of normal cells. Our study addresses the issue of cellular damage induced by the delivery of anticancer drugs from LNs. The results of this study indicate that even though LNs are capable of depositing a lethal dose of drugs, the drug-loaded LNs do not induce significant cellular damage. Unlike drug-loaded micelles (e.g., DSPC-DSPE-PEG2000), which form large aggregates in blood due to the positive charge of their constituent cationic block, LN-drugs do not produce such a large aggregation. In addition, unlike injection of the free drug at the same dosage, liposomal drug delivery minimizes adverse effects related to large aggregates of the drug-loaded LNs, which have been implicated in the adverse effects of nanomaterials.^[@ref24],[@ref43]^

In conclusion, we have demonstrated that the lipid composition of a LN-based delivery system can be optimized to reduce the probability of drug leakage and ensure targeted delivery of anticancer drugs. The resulting LN-based drug delivery systems provide a novel method of cancer therapy and minimize the adverse effects of free-drug therapies due to the large aggregates of the drug in blood.

Experimental Section {#sec4}
====================

Instrumentation and Methods {#sec4.1}
—————————

Optical spectrophotometry, dynamic light scattering, zeta potential measurements, fluorescence spectroscopy, and HPLC were conducted using a Cary 50 spectrophotometer (Varian), Zetasizer Nano ZS (Malvern Instruments), Cary Eclipse fluorescence spectrophotometer (Varian), Zetasizer Nano ZS (Malvern Instruments), and Shimadzu HPLC, respectively.

The lipids used in this study were purchased from Avanti Polar Lipids: 1,2-dioleoyl-*sn*-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-*sn*-gly

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