Rapidly Dissolving Microneedles for the Delivery of Steroid-Loaded Nanoparticles Intended for the Treatment of Inflammatory Skin Diseases

Abstract

Drug delivery through the skin has immense advantages compared to other routes of administration and offers an optimal way to treat inflammatory skin diseases, where corticosteroids are the cornerstone of topical therapy. Still, their therapeutic efficiency is limited due to inadequate skin permeability, potential side effects, and reduced patient compliance. To overcome these drawbacks, we propose a drug delivery system consisting of dexamethasone (DEX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) incorporated in sodium alginate (SA) microneedles (MNs) as a minimally invasive dosage form for controlled drug release. Drug-loaded PLGA NPs were prepared by a nanoprecipitation method with a high encapsulation yield. They exhibited a controlled release pattern over 120 h. A modified vacuum-deposition micromolding method was used to load the obtained DEX-NPs into the tips of dissolving MNs. The NP-MNs showed improved insertion capabilities into the skin-simulant parafilm model and enhanced mechanical strength when tested against different static forces compared to their counterparts (SA-MNs). The results of an MN dissolution study following application to ex vivo chicken skin and agarose gel indicate that the NP-loaded segments of MNs dissolve within 15 s, in which the NPs are released into the skin. Taken together, the incorporation of DEX-NPs into SA-MNs could be a promising approach to bypass the limitations of conventional topical treatment of skin diseases, allowing for self-administration, increased patient compliance, and controlled drug release.

Hydrogel Microneedles with Programmed Mesophase Transitions for Controlled Drug Delivery

“…As displayed in Figure , the MNs underwent deformation that can be clearly observed when compared to the original state, in which the sharp tips of MNs presented more and more bending after putting with 50 g (∼4.9 mN/needle) to 1000 g (∼98 mN/needle) weights on MNs. However, the MNs remained intact and did not break, indicating their good mechanical strength and potential competency for transdermal drug delivery. ,, …”

“…The insertion test was performed using eight stacked layers of Parafilm (∼140 μm each) as a skin simulant to investigate the penetration ability of the MN arrays as well as the insertion depth. − This skin-simulant model was developed and validated by Larrañeta et al, showing that the insertion profiles obtained are consistent with the insertion depths obtained with optical coherence tomography (OCT), and the force that was used in this test gave insertion profiles equivalent to those obtained using neonatal pig skin . Briefly, the obtained MNs were inserted manually into the Parafilm layers, held for 30 s, and then removed.…”

“…MN arrays were prepared based on our previous work, using a modified vacuum-deposition casting method . Silicone MN molds were used to fabricate MN arrays of 10 × 10 pyramid-shaped microneedles, with 500 μm needle height, 200 μm base diameter, and interspacing of 500 μm.…”

“…However, the MNs remained intact and did not break, indicating their good mechanical strength and potential competency for transdermal drug delivery. 26,52,53 Taken together, incorporating PEG with high molecular weights into the MN formulations led to an improvement in the mechanical properties due to the increased polymeric chain density at the MN tips. 26,54 Furthermore, PEG was previously found to increase the entanglement of the polymeric chains, 23 and this was further reinforced by the analysis of the thermal behavior of the polymer blend of the triblock polymer and PEG 35 kDa using differential scanning calorimetry (DSC).…”

“…These MNs would transform into enzymatically degradable drug eluting hydrogels upon their penetration into the skin and absorption of interstitial fluid, followed by their in situ transition into gel microparticles, which can enhance drug release and be fully degraded by target enzymes into soluble hydrophilic polymers. Herein, as a proof of concept, the triblock polymeric amphiphile is composed of a central hydrophilic poly(ethylene glycol) (PEG, 10 kDa) block conjugated with two hydrophobic dendritic branching units functionalized with ester-based nonyl end-groups (Tri-C9), which can potentially be cleaved by skin esterases 25 (Figure 1), and dexamethasone (DEX) was used as a model drug.…”