A temperature-sensitive drug release system based on phase-change materials

Abstract

Phase-change materials (PCMs), including 1-tetradecanol with a melting point at 38–39 °C and dodecanoic acid with a melting point at 43–46 °C were exploited as thermosensitive materials to demonstrate a new temperature-regulated drug release system. In this approach, colloidal particles containing FITC-dextran were embedded in the PCM matrix and processed as spheres or rods. When temperature was below the melting point of the PCM, there was no release of FITC-dextran due to the hydrophobic nature of the PCM. As the temperature was increased beyond the melting point, the PCM began to melt, the encapsulated particles leached out, and eventually FITC-dextran was released from the colloidal particles. By using colloidal particles made of gelatin, chitosan, and poly(lactic-co-glycolic acid) that have different solubility in water, we could manipulate the release pattern of FITC-dextran. We also demonstrated a dual temperature-regulated drug release system by incorporating two different PCMs into the same device. As an attractive feature, we could easily alter the initiation temperature and release pattern of drugs by judiciously selecting different combinations of PCMs and materials for the colloidal particles.

Figure 1

a) Fluorescence and b) confocal micrographs of uniform 1-tetradecanol beads containing gelatin particles loaded with FITC-dextran. c) Time-lapse fluorescence micrographs showing melting of the 1-tetradecanol bead and release of FITC-dextran from the gelatin particles as the temperature was gradually increased by adding warm water (60 °C) under gentle stirring. The insets are schematic diagrams showing the three major steps involved in the release of FITC-dextran: melting of 1-tetradecanol beads, leaching out of gelatin particles, and release of FITC-dextran as gelatin is being dissolved.

Figure 2

Optical micrographs of a) gelatin, b) chitosan, and c) PLGA microbeads containing FITC-dextran. d) Schematic diagram for fabricating a PCM-based block containing the uniform microbeads loaded with FITC. The scale bars are 100 μm.

Figure 3

a) Time-lapse fluorescence micrographs showing the release of FITC-dextran from gelatin microbeads encapsulated in a 1-tetradecanol block. The temperature was gradually increased by adding warm water (60 °C) under gentle stirring. b) Release profiles at 37 and 39 °C for FITC-dextran from gelatin, chitosan, and PLGA microbeads encapsulated in the 1-tetradecanol blocks (n = 3). Cumulative FITC-dextran release (%) was defined as the ratio of released amount of FITC-dextran at a given time divided by the theoretical initial amount encapsulated.

Figure 4

Release profiles (n = 3) at 37, 39, and 44 °C for FITC-dextran from gelatin microbeads encapsulated in a dual PCM block fabricated from 1-tetradecanol and dodecanoic acid.