Characterization of polymeric microneedle arrays for transdermal drug delivery

Abstract

Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs) were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS), where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN) precision was ranging from ± 0.18 to ± 1.82% for microneedle height, ± 0.45 to ± 1.42% for base diameter, and ± 0.22 to ± 0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.

Figure 1. Digital photographs of PDMS micromold parts, and chemical formulas of PDMS.

(A) Digital photograph of a 10×10 PDMS micromold fabricated from the pyramidal master template. (B) Top view of the PDMS microholes. (C) Digital representation of the cross-section of the PDMS micromold assembled by conventional micromolding techniques from pyramidal master templates (scanned with an Olympus SZX7 Stereo Microscope; captured using an Olympus C5060 WZ digital camera, Olympus Corporation, Lake Success, NY; and sorted with Adobe® Photoshop® CS5 Extended, Version 12.0×64, Adobe Systems Inc., San Jose, CA). (D) Digital image of a 2×3 needle PDMS micromold. (E) Chemical formulas for polysiloxane and PDMS (Drafted with Chem Sketch Freeware 12; Advanced Chemistry Development, Inc., Ontario, Canada).

Figure 2. Digital photographs of sections from 10×10 dissolvable MNs fabricated from PDMS micromolds.

(A) SA MNs. (B) HPC-M MNs. (C) HPC-H MNs. (D) Cross-linked swellable PVA-gelatin MNs. (E) Chitosan MNs. (F) PLGA MNs.

Figure 3. SEM photographs of parts from 10×10 MN arrays.

(A)–(E) show polymeric MN arrays that were replicated from the pyramidal master template. (A) SA MNs. (B) HPC-M MNs. (C) HPC-H MNs. (D) Cross-linked PVA-gelatin MNs. (E) Chitosan MNs.

Figure 4. Micrographs of polymeric MN axial fracture and transverse fracture tests.

(A) Digital photograph of SA MN pressed against the metal mill during axial fracture force measurement with the micromechanical tester (Instron® Model 5969; Instron, Norwood, MA). (B) MN shafts were transversely pressed against the metal mill for measurement of the transverse fracture force by way of the micromechanical tester (Instron® Model 5969, Instron, Norwood, MA).

Figure 5. Results of mechanical analysis of SA and PLGA MN.

(A) Mechanical analysis of polymeric 10% (w/w) SA MNs under axial loading. MN failure was interpreted as the sudden decrease in force. (B) Mechanical analysis of polymeric PLGA (50∶50) MNs under axial loading. MN failure was interpreted as the point at which the force became saturated. (C) Mechanical analysis of polymeric 10% (w/w) SA MNs under transverse loading. MN failure was interpreted as the sudden decrease in force. (D) Mechanical analysis of polymeric PLGA (50∶50) MNs under transverse loading. MN failure was interpreted as the sudden decrease in force