Table 2.
Ex vivo and in vitro studies assessing the efficacy and permeability of micronutrient delivery transdermal patches.
| First author | Origin | Study type | Tested nutrient | Micronutrient delivery form | Delivery method | Samples | Control | Temperature control | Results | Issues |
|---|---|---|---|---|---|---|---|---|---|---|
| Juluri [33] | USA | in vitro | Iron | ID | ID patch (transdermal Polyolefin foam patch loaded with 200 μL of 50 mg/mL ID) with skin pretreated with MNs (2′) | Male hairless rat skin (Charles River, Wilmington, MA) |
ID via IP delivery | ✓ | The cumulative amount of ID permeated at the end of 6 h was 10.28 ± 0.45 μg/cm2. After 6 h of permeation 2.48 μg/mg of ID was retained in the skin. | |
| Hutton [35] | UK | in vitro | Vitamin K | Vitamin K | Vitamin K MN dissolving arrays (using an aqueous blend of Gantrez® S-97 and Tween® 80) | Neonatal porcine skin | – | ✓ | Permeation of vitamin K through porcine skin occurred throughout the 24 h experiment, with MN arrays delivering 1.80 ± 0.08 mg of vitamin K during this time (35% of the administered dose). | Small study duration. Did not measure the time needed to dissolve MN arrays. |
| Kim [14] | S. Korea | ex vivo | Vitamin D3 | PLGA nanoparticles loaded with Vitamin D3 and PVA stabilizer | Coated MN patch | Porcine skin (Cronex, Hwasung, South Korea) | Transdermal cream with identical vitamin D3 amounts and a penetration enhancer [45] |
– | Despite the fact that the transdermal cream contained a chemical penetration enhancer, the MN system showed 5-fold better delivery performance. | Is the encapsulation capacity able to carry daily human needs? 25 μg were used |
| Maurya [30] | India | ex vivo | Iron | FPP loaded HA | MN (polydimethylsiloxane micromold) patch | Excised rat skin | – | – | The mean Fe recovered from the skin after 5′ application of the patch was 130.5 ± 18.6 mg (66% of the MN total load). | |
| Modepalli [31] | USA | ex vivo | Iron | 1) FPP patches 2) FPP patches with skin pretreated with MN injection 3) FPP patches + IN 4) FPP patches + IN, with skin pretreated with MN injection |
Patch: FPP loaded HPMC transdermal patch MN: AdminPen 600 stainless steel with an area of 1 cm2 and 187 MNs with a height of 500 μm (nanoBioScience LLC. Alameda, CA) applied for 2′ |
Excised rat abdominal skin | – | ✓ | The lowest amount of FPP was permeated at patches alone, followed by patches with IN, MN pretreated patches and finally the MN + IN pretreated patches induced the greatest (~ 44-fold) enhancement in the flux (51.24 ± 7.55 μg/cm2/h) over passive permeation. | |
| Modepalli [29] | USA | in vitro | Iron | FPP in soluble MN arrays | Soluble (15% w/w PMVE/MA) MN arrays patch | Human HDF [CCD1093Sk (ATCC® CRL2115™)] cell lines (ATCC, Manassas, VA) | – | – | Based on the safety and toxicity study, the amount of FPP in the patches was safe and non-toxic. | Feasibility study |
FPP: ferric pyrophosphate; HA: hyaluronic acid; HDF: Human Skin Fibroblast; HPMC: Hydroxypropyl methyl cellulose; ID: iron-dextran; IN: iontophoresis at a current strength of 0.15 mA/cm2; MN: Microneedle; MTS: mitochondrial activity; PLGA: Poly (lactic-co-glycolic acid); PMVE/MA: poly methylvinylether/maleic acid; PVA: polyvinyl alcohol.