Rapamycin-loaded
polycaprolactone nanoparticles (RAPA-PCL NPs)
with a polydispersity index of 0.006–0.073 were fabricated
by antisolvent precipitation combined with micromixing using a ringed
stainless steel membrane with 10 μm diameter laser-drilled pores.
The organic phase composed of 6 g L–1 PCL and 0.6–3.0
g L–1 RAPA in acetone was injected through the membrane
at 140 L m–2 h–1 into 0.2 wt %
aqueous poly(vinyl alcohol) solution stirred at 1300 rpm, resulting
in a Z-average mean of 189–218 nm, a drug
encapsulation efficiency of 98.8–98.9%, and a drug loading
in the NPs of 9–33%. The encapsulation of RAPA was confirmed
by UV–vis spectroscopy, XRD, DSC, and ATR-FTIR. The disappearance
of sharp characteristic peaks of crystalline RAPA in the XRD pattern
of RAPA-PCL NPs revealed that the drug was molecularly dispersed in
the polymer matrix or RAPA and PCL were present in individual amorphous
domains. The rate of drug release in pure water was negligible due
to low aqueous solubility of RAPA. RAPA-PCL NPs released more than
91% of their drug cargo after 2.5 h in the release medium composed
of 0.78–1.5 M of the hydrotropic agent N,N-diethylnicotinamide, 10 vol % ethanol, and 2 vol % Tween
20 in phosphate buffered saline. The dissolution of RAPA was slower
when the drug was embedded in the PCL matrix of the NPs than dispersed
in the form of pure RAPA nanocrystals.