Hardly water-soluble drug-loaded gelatin nanoparticles sustaining a slow release: preparation by novel single-step O/W/O emulsion accompanying solvent diffusion

摘要

Paclitaxel (PTX)-loaded gelatin nanoparticles (NPs) were prepared, for the first time, by novel O/W/O emulsion with a single-step emulsion process accompanying solvent diffusion, in contrast to the conventional double-step emulsion processes. Linoleic acid was chosen among the natural fatty acids as the exterior medium for the single-step emulsion process accompanying solvent diffusion. The size mean and zeta potential of the PTX-loaded gelatin NPs in their suspension were 164.95 nm (+/- 6.43 nm) distributed with a polydispersity of 0.074 (+/- 0.046) and -23.85 mV (+/- 12.66 mV), respectively. The size of the PTX-loaded gelatin NPs prepared in this study was the smallest among the reported sizes of PTX-loaded gelatin NPs, which would contribute to the enhanced permeability and retention (EPR). In addition, TEM showed that the loaded PTX was located mostly inside the gelatin NPs unlike previous investigations. Accordingly, the conceptual model of the designed PTX-loaded gelatin nanoparticle was introduced. Sustaining a slow PTX release on a day-time scale without an initial burst release into a release medium was observed along with a delay of more than 2 days (i.e., 50 h) before a bursting PTX release from 50 to 70 h despite the addition of a protein degrading enzyme. The observed PTX-loading efficiency was 54.5%. This loading efficiency was greater than that of previous study using gelatin of bloom 75-100 of Lu et al. to prepare PTX-loaded gelatin NPs using a desolvation method.