PMC

Dissolving microneedles for transdermal drug delivery. (a) Microneedle master-structure (600 μm in height and 300 μm wide at base) used to mold dissolving microneedles made of (b) CMC, (c) amylopectin and (d) BSA. The master-structure was imaged by scanning electron microscopy and the molded microneedles were imaged by brightfield microscopy.

Dissolution kinetics of microneedles after insertion in skin. (a) CMC pyramidal microneedles imaged by brightfield microscopy before insertion and (b) 10 sec, (c) 1 min, (d) 15 min, and (e) 1 h after insertion into pig cadaver skin.

Swelling of dissolving microneedle patch backing layer after insertion into skin using a Franz cell. (a) A patch of CMC pyramidal microneedles containing sulforhodamine inserted into skin for 15 h shows extensive swelling of the backing layer. (b) A backing layer of CMC that contains no microneedles (negative control) placed on the surface of skin for 15 h shows little swelling. Human epidermis was used. Imaging was by brightfield microscopy.

Dissolving microneedles for sustained release. (a) CMC pyramidal microneedles encapsulating sulforhadamine only in the backing layer. (b) Skin surface showing sulforhodamine delivered into the skin by insertion of the microneedles shown in part (a) for 12 h imaged by brightfield microscopy. (c) Cross-sectional histological image of skin pierced by the microneedles shown in part (a) for 12 h and imaged by an overlay of brightfield and fluorescence microscopy. Pig cadaver skin was used.

Protein stability after encapsulation and release from dissolving microneedles. (a) Circular dichroism spectrum of untreated lysozyme (negative control); lysozyme encapsulated in CMC microneedles and released by dissolution in PBS; lysozyme encapsulated in CMC microneedles and released by dissolution in PBS after 2 months storage at room temperature; and lysozyme denatured at 80ºC for 30 min (positive control). (b) Enzymatic activity of untreated lysozyme (A, negative control); lysozyme mixed with dissolved placebo CMC microneedles (B, negative control); lysozyme encapsulated in CMC microneedles and released by dissolution in PBS (C); lysozyme encapsulated in CMC microneedles and released by dissolution in PBS after 2 months storage at room temperature (D).

Transdermal release profile from dissolving microneedles patches. (a) Cumulative release of sulforhodamine encapsulated at 10 wt% in the pyramidal microneedles and the backing layer of patches made of CMC and amylopectin. (b) Cumulative release during the initial release period of sulforhodamine encapsulated at 0 wt% in the pyramidal microneedles and at 10 wt% or 30 wt% in the backing layer of CMC patches. Human cadaver epidermis was used. Average values are shown with standard error bars based on 3 replicate measurements.

Mechanical behavior of dissolving microneedles. Force measured as a function of microneedle displacement while pressing against a rigid surface for (a) CMC and PLA microneedles having conical and pyramidal geometries and (b) pyramidal microneedles made of PLA, amylopectin, BSA, CMC, and a mixture of 80/20 wt% CMC/BSA. Conical microneedles measured 800 μm in height and 200 μm in base diameter. Pyramidal microneedles measured 600 μm in height and 300 μm in base width. The graphs contain data representative of 5 replicate measurements each.

Imaging microneedle insertion into pig cadaver skin. (a) View of the back side of a CMC microneedle patch applied onto the surface of the skin. (b) CMC pyramidal microneedles after insertion into the skin for 3 s. (c) Skin stained with tissue marking dye to identify the sites of needle penetration after insertion of CMC pyramidal microneedles. (d) Cross-sectional image of H&E-stained skin at a site of microneedle penetration (SC: stratum corneum, VE: viable epidermis, and D: dermis). All images viewed by brightfield microscopy.

Dissolving microneedles for bolus delivery into skin. (a) CMC pyramidal microneedles encapsulating sulforhodamine B within the microneedle shafts, but not in the backing layer. (b) Skin surface showing sulforhodamine delivered into the skin by insertion of the microneedles shown in part (a) for 5 min imaged by brightfield microscopy. (c) Cross-sectional histological image of skin at the penetration site of two adjacent microneedles shown in part (a) inserted for 5 min and imaged by brightfield (c1) and fluorescence (c2) microscopy. (d) Cross-sectional histological image of skin pierced by an array of sulforhodamine-containing microneedles for 1 h and imaged by an overlay of brightfield and fluorescence microscopy. Pig cadaver skin was used.