Optically monitored drug delivery patch based on porous silicon and polymer microneedles

Abstract

Fabrication and characterization of an optically monitored hybrid patch for local administration of drugs, based on polymeric micro-needles and a porous silicon free-standing membrane, are reported. The micro-needles are realized by an innovative photolithographic approach that allows fine tuning of geometrical parameters, using polyethylene glycol and a commercial photo-catalyzer. The porous silicon multilayer not only increases the storage of a relevant amount of the drug, but also offers a continuous, naked-eye monitoring of the drug delivery process. As a proof-of-concept experiment, we report our results on the release of a dye molecule (fluorescein, 332 Da) in a phosphate saline buffer.

Keywords: (160.5470) Polymers; (170.0170) Medical optics and biotechnology; (310.6845) Thin film devices and applications.

Fig. 1

Microneedles array process flow: photolithographic standard approach allows low cost fabrication of large area MNs array. Steps 1-6 are recalled in text in Fabrication process paragraph.

Fig. 2

Schematic of hybrid patch assembling: the porous silicon oxidized free-standing membrane is placed on PEGDA support (a); then the active molecules are loaded in its spongy matrix (b) and the MNs array is bonded by UV exposure (c and d). In the inset, microphotograph by electron scanning microscopy of PSi real sample and a digital image of the assembled patch are reported.

Fig. 3

MNs array characterization: (a) MNs array flexibility; (b) micro-images of a single needle; (c) macroscopic view of MNs; (d) tip measurement. The MNs array on PEGDA has good flexibility useful for patch applications. The MNs have highness, shapes and curvature radii tunable by changing process parameters.

Fig. 4

Sketch of device operation: the PSiM is loaded with fluorescein molecules (a), fluorescein diffuses into the MNs nanoporous (b) and it is released into the PBS solution as effect of the MNs swelling(c).

Fig. 5

(a) Top view of the device acquired in bright field mode: the blue line underlines the profile of the porous silicon membrane placed under the microneedles (right side) with respect to the only microneedles (left side); (b) Top view of the device acquired in fluorescence mode with the same field of view of (a): the image shows that only the area overlapping the porous silicon membrane is fluorescent (right side). (c) Fluorescence intensity of areas inside the red rectangles calculated using ImageJ software; (d) Lateral view of the device acquired in fluorescence mode: the blue line underlines the profile of the porous silicon membrane placed under the microneedles. (e) A single microneedle detached from the device after fluorescein loading shows that the fluorescein is almost uniformly distributed from the base to the tip.

Fig. 6

Spectroscopic reflectometry (a) and naked eye (b) characterizations after oxidation, fluorescein loading and release.

Fig. 7

Calibration curve of fluorescein loading into Bragg mirror optical structure b); correspondent optical spectra a).

Fig. 8

Fluorescence intensity of the device changes as function of time of fluorescein release in PBS. The control shows that intensity fluorescence decreasing is not due to fluorescence decay.

Fig. 9

Comparison between the estimated fluorescein released in PBS and data of in vitro release as reported in ref [16].