Table 5.
Design characteristics and the reported findings of non-transdermal insulin microneedles.
| Insulin microneedles | Polymers/excipients added | Morphological dimensions | Penetration force | Mechanical strength | MN (grind) insertion angle | Insulin loading | Findings | Reference |
|---|---|---|---|---|---|---|---|---|
| Intraoral MN | Biodegradable PVP | 750 μm long and 200 μm wide (up to 1 mm length) | 10 N | Strong enough to penetrate the palate. | – | Could load up to 2 mg of INS. 1.0 ± 0.2 mg was localized on the MN tips. |
1.0 mg INS delivered within 5–30 s (swine) | Caffarel-Salvador et al. (2021) |
| Intragastric SOMA (self-orienting millimeter scale applicator) | Biodegradable HPMC, polyethylene oxide (PEO 200 K), and dissolvable sucrose. | Conical MN; 1.7 mm in height and 1.2 mm in diameter. Total millipost length: 7 mm |
1 N | 20.0 ± 0.7 MPa | 10° angle | 0.3–0.7 mg per pill. | Bioavailability: 10% (10–70 pM INS for 3.5 h). INS delivery coefficient: 111.1 pM/mg m−M. INS plasma concentration was comparable to S.C. INS injection. Zero-order release kinetics. Penetrated until muscularis mucosa above the submucosal layer of the stomach. |
Abramson et al. (2019) |
| Intragastric l-SOMA (liquid-injectable SOMA) | MN: polyoxymethylene (non-biodegradable) Plunger: polyphenylene ether (non-biodegradable) Elastomer: Kraiburg |
Needle length optimized to 4.5 mm penetration depth. | 5.7 ± 2.7 N for 4.5 mm penetration depth | 4.7 N | 12.5 ± 2° angle | Up to 4 mg could be loaded. In vivo analysis done with 4 IU of INS (0.14 mg), injection flow rate: 21 μL/s |
Bioavailability: 51 ± 16% for 2 h (30–81% in 2 h; n = 7) (80 μL delivered into the submucosal space) The set-up is made of non-biodegradable materials and should be eliminated from the body. Liquid insulin creates instability issues |
Abramson et al. (2019) |
| Intestinal LUMI (luminal unfolding microneedle injector) | Arm with MNs: 75% 200 kDa PEO and 25 % Soluplus®, a biodegradable polymer. Elastomer: Mediprene Coating: Eudragit L-100/55 (20 μm thick dissolves at pH 5.5) |
1 mm length and 0.4 mm base diameter. | 0.20–0.28 N (human tissue) or 3 N for 30 MNs. | 0.41 ± 0.06 N (13 mN per microneedle) | 30° angle | 0.5 mg per LUMI | LUMI in vivo: 40% systemic uptake. Directly applied MN intestinal patch: 80% systemic uptake. INS delivery coefficient: 81.8 pM/mg·m−M. Safe deployment of LUMI in the small intestinal mucosa. Delayed release due to gastric emptying time. Long-acting INS could be delivered in this way. |
Abramson et al. (2019) |
| Intestinal IMNMs (insulin microneedle micro motors) | MN: 30% methacryloyl gelatin (GelMA) and 15% PVA: MW 89,000–98,000 Separator: PVA 30%, MW 13,000–23,000 |
30 μm of tip diameter and 500 μm in height. | Penetration depth is 240 μm | 0.34 N | – | ≈18 U of INS administered as per 6 U/kg rabbit weight. | Degradation time for MN: 40 min. Separator removal after 30 min of implantation. INS released rapidly for 2 h and then a sustained release pattern was seen for 24 h. The whole set up to be enclosed in an enteric-coated capsule to deliver the micromotor MNs intact to the intestine. |
Zhang et al. (2022) |
| Colonic robotic micro injectors | INS-loaded chitosan gel coats | 450 μm length and INS-chitosan coating thickness 5 μm. | – | 0.4–0.5 MPa | – | Each microinjector holds 300 μIU of INS | INS delivery coefficient of 1036.5 pM/mg·m−M. | Ghosh et al. (2022) |
| Tumbler-inspired self-orienting MN for colon delivery | Detachable layer: PVA and PVP degradable in colonic juice (within 6 min) Degradable MN: PVA, chitosan, maleilated dextran, and polycaprolactone |
– | Full penetration 0.058 N/needle for a penetration depth of 240 μm | – | @90° fall the reorientation of the device is within 0.35 s | Mechanistic study | The low center of gravity on the robotic shell makes the device self-orient vertically to its solid bottom and gets anchored to the colon mucosa for the MN to penetrate and release INS. Polymer-based dissolving MN used for long-term drug release. |
Huang et al. (2023) |
| Powder-carrying microneedles (PCM) for transdermal implant | Micro-shells: carboxymethyl cellulose (10%)-biodegradable, biocompatible and viscous. | 800.3 ± 1.4 μm height and 450.5 ± 2.1 μm diameter. Above CMC protective layer thickness 30 μm |
100% micro shells penetration | PCM: 0.040 ± 0.008 N DMN: 0.033 ± 0.005 N |
– | PCM carries 225.5 ± 8.6 μg of INS. DMN carries 90.4 ± 3.1 μg of INS |
Increasing CMC concentration reduced the polymer microcavity dimension and increased its thickness. The amount of encapsulated cargo increased in PCM than the amount in dissolvable MN (DMN) prepared with reconstituted drug. Tmax: 5.40 ± 1.17 h Cmax: 0.96 ± 0.15 ng/mL AUC: 2.56 ± 0.94 ng·h/mL Bioavailability: 61.51% |
Kim et al. (2020) |