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.2021 Oct 26;31(44):2103359.
doi: 10.1002/adfm.202103359. Epub 2021 Jun 21.

Efficient Drug Delivery into Skin Using a Biphasic Dissolvable Microneedle Patch with Water-Insoluble Backing

Affiliations

Efficient Drug Delivery into Skin Using a Biphasic Dissolvable Microneedle Patch with Water-Insoluble Backing

Song Li et al. Adv Funct Mater..

Abstract

Dissolvable microneedle patches (MNPs) enable simplified delivery of therapeutics via the skin. However, most dissolvable MNPs do not deliver their full drug loading to the skin because only some of the drug is localized in the microneedles (MNs), and the rest remains adhered to the patch backing after removal from the skin. In this work, biphasic dissolvable MNPs are developed by mounting water-soluble MNs on a water-insoluble backing layer. These MNPs enable the drug to be contained in the MNs without migrating into the patch backing due to the inability of the drugs to partition into the hydrophobic backing materials during MNP fabrication. In addition, the insoluble backing is poorly wetted upon MN dissolution in the skin, which significantly reduces drug residue on the MNP backing surface after application. These effects enable a drug delivery efficiency of >90% from the MNPs into the skin 5 min after application. This study shows that the biphasic dissolvable MNPs can facilitate efficient drug delivery to the skin, which can improve the accuracy of drug dosing and reduce drug wastage.

Keywords: dissolvable microneedle patch; drug diffusion; hydrophobic surfaces; skin delivery efficiency; transdermal drug delivery; water insoluble backing.

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Conflict of interest statement

Conflict of Interest M.P. has a financial interest in the MNP technology discussed here as a consultant, inventor, and company founder (Micron Biomedical); the associated conflict of interest is managed by Georgia Tech.

Figures

Figure 1.
Figure 1.
Design of MNP fabrication process using water-soluble or water-insoluble patch backings. In this design, each MN is attached to the patch backing containing pedestals on which the MNs are mounted. While the overall process of fabrication (mold-filling and drying, step 1–3) and skin application (applying on skin and removal, step 3–5) are the same, the two processes yield MNPs with different properties: A) Water-soluble backing causes significant drug migration from MNs to the backing layer during the drying process (step 3), and it also retains drug residue when removing the patch from the skin (step 5). B) Water-insoluble backing limits drug migration from MNs (step 3), and it also prevents retention of dissolved drug on the pedestals of the patch backing when removing from the skin (step 5).
Figure 2.
Figure 2.
Morphological examination of MNPs before and after application on porcine skin. Representative images of MNPs containing a 10 × 10 array of MNs with A) a hydrophilic backing made of PVA and sucrose or B) a hydrophobic backing made of PS. Representative side views of two MNs mounted on patch backing pedestals made of C) hydrophilic materials showing red dye in the MNs and the pedestals, or D) hydrophobic materials showing localization of the red dye only in the MNs. E) Representative image of pig skin after MNP application ex vivo and staining of micropores with gentian violet. The MN insertion sites in the skin correspond to the 10 × 10 pattern of MN in the MNP.
Figure 3.
Figure 3.
Representative fluorescence microscopy images of SRhB-loaded MNs using different backings. The MNs were made using casting solution with SRhB with red fluorescence. The water-soluble backings were prepared using casting solution with Dex-FITC and the insoluble backings were prepared using casting solution with Cou-6, both of which have green fluorescence. MNs are shown with imaging by bright field, with only the red-fluorescence channel showing the location of SRhB, with only the green fluorescence channel showing the location of Dex-FITC or Cou-6, or with both the red- and green-fluorescence channels displayed to show the yellow color representing colocalization. These images show that SRhB diffused significantly into the water-soluble backing (left column) but did not migrate into the insoluble backing (right column). Scale bar = 500 μm.
Figure 4.
Figure 4.
Representative CLSM images of MNs loaded with SRhB (panel A) or Alexa Fluor 568 labeled tetanus toxoid (TT-AF568) (panel B), showing the cross-sections of MNs and distribution of model drugs along the MNs. A) Using water-soluble backing (left column), SRhB in the MNs and Dex-FITC in the backing were colocalized to reveal the migration of SRhB from MNs to the pedestal region of the backing; while using insoluble backing (right column), a clear interface between MNs and backing was observed to indicate no migration of SRhB into the backing. B) Using soluble backing (left column), colocalization of TT-AF568 and Dex-FITC was not as significant as the case of SRhB, indicating little migration of TT-AF568 to the backing; using insoluble backing (right column), a clear interface was still observed to indicate no migration of TT-AF568 into the backing.
Figure 5.
Figure 5.
Impact of MNP backing type on the drug residue left on the backing. A) Static water contact angle (n = 6) on insoluble PS film (left) or soluble PVA/ sucrose film (right). B) Representative images comparing SRhB residue on insoluble and soluble MNP backings after dipping into aqueous solutions containing various concentrations of polyacrylic acid (PAA) and sucrose; the insoluble backing had much less SRhB residue on the surface. Scale bar = 5000 μm. C) Quantitative comparison of SRhB residue on insoluble and soluble patch backings after dipping into aqueous solutions of PAA and sucrose (100% level is the SRhB amount on the soluble backing from 15% PAA +30% sucrose). *p < 0.001 (Student’st-test). Data are shown as mean ± SD,n = 4.
Figure 6.
Figure 6.
Kinetics of delivering different-sized model drugs into porcine skin ex vivo using MNPs with water-soluble or insoluble backing: A) SRhB, B) INS, and C) TT. Drug dose in all MNPs was 5 μg per MNP. Data are shown as mean ± SD,n = 4 for SRhB,n = 6 for INS and TT.
See this image and copyright information in PMC

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