Encapsulation and Controlled Release of Rapamycin from Polycaprolactone Nanoparticles Prepared by Membrane Micromixing Combined with Antisolvent Precipitation.

Abstract

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.