Co-precipitation of asiatic acid and poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) using rapid expansion of subcritical solutions into liquid solvents

Poly(l-lactide) (PLLA) nanoparticles loaded with asiatic acid (AA) were successfully produced by rapid expansion of a subcritical solution into an aqueous receiving solution containing a dispersing agent. A mixture of carbon dioxide (CO₂) and ethanol (EtOH) with a weight ratio of 1:1 was used as the solvent for AA and PLLA. Two surfactants, Pluronic F127 and sodium dodecyl sulfate were employed. The former was found to be more effective for stabilizing AA-loaded PLLA nanoparticles, as a rapid expansion into a 0.1 wt% Pluronic F127 solution produced a stable nanosuspension consisting mainly of well-dispersed, individual nanoparticles. The effects of rapid expansion-processing conditions—AA to PLLA weight ratio and pre-expansion temperature (T_pre)—on the size and morphology of composite nanoparticles, and the loading capacity and entrapment efficiency of AA in PLLA nanoparticles, were systematically investigated. It was found that AA-loaded PLLA nanoparticles with a size range of 30–100 nm were consistently fabricated by rapid expansion at T_pre of 70–100 °C and AA to PLLA weight ratios of 1:2 and 1:4, and with a constant pre-expansion pressure of 330 bar. The T_pre and AA to PLLA weight ratio had no significant effects on the size of the nanoparticles. The AA to PLLA weight ratio is a controlling parameter for both the loading capacity and the entrapment efficiency of AA in PLLA nanoparticles. The loading capacity and entrapment efficiency increased from 8–11 to 16–21 wt%, and 38–57 to 50–62 wt%, respectively, when the AA to PLLA weight ratio changed from 1:4 to 1:2. However, increasing the T_pre from 70 to 100 °C decreased both the loading capacity and entrapment efficiency of AA in PLLA nanoparticles by ~20–30%.