Novel Long-Circulating Lipid Nanocapsules

Abstract

Purpose. To develop and evaluate novel long-circulating lipid nanocapsules (LN) designed for tumor delivery of lipophilic drugs.

Methods. Nanocapsules were produced by a solvent-free phase inversion process and were coated with polyethylene glycol-distearoylphosphatidylethanolamine conjugate (DSPE-PEG) during preparation or by a post-insertion step. In vivo studies were conducted in rats to assess LN pharmacokinetics and biodistribution.

Results. Post-insertion of DSPE-PEG appeared to be a convenient and effective method of obtaining LN of controlled sizes with high PEG density at their surface. After intravenous injection to rats, PEGylated lipid nanocapsules obtained by the post-insertion method exhibited long-circulating properties. Up to 50% of the injected dose was still present in the blood 8 h after administration for LN containing 6 mol% PEG 5000 or 10 mol% PEG 2000. This represented an area under the blood concentration-time curve of almost 70% that of liposomes used in the Doxil® formulation.

Conclusion. With a simple solvent free-process, it was possible to produce long-circulating LN of controlled sizes. Such LN could prove useful for the passive delivery of lipophilic anticancer drugs to solid tumors.