QuadMedicine, Inc.

Separable and dissolvable microneedle array patch based primarily on hyaluronic acid is designed for the topical delivery of baricitinib in alopecia areata (AA) therapy. Locoregional application of a separable microneedle array patch (S-MAP) may avoid the systemic side effects of oral administration and can be administered without pain compared with typical intradermal injections. Baricitinib (which has poor aqueous solubility) is evenly suspended with sodium carboxymethylcellulose. Subsequently, the mixture is blended with other pharmaceutical excipients, such as hyaluronic acid, sucrose, and Tween 80, to fabricate the S-MAP. Crystalline baricitinib transformed into an amorphous state during the drying process, which may have contributed to complete drug dissolution in the aqueous buffer within 60 min. Proper insertion of a baricitinib-loaded S-MAP into porcine skin tissue and mouse skin is demonstrated using optical coherence tomography and near-infrared fluorescence imaging, respectively. Topical administration of the baricitinib-loaded S-MAP system to the AA lesion of mouse models resulted in significantly higher hair growth compared with the control group (S-MAP: 82 % vs. control: 31 %, p < 0.05). These findings suggest that the baricitinib S-MAP system can be used efficiently and safely, while affording pain-free and self-medication properties, for the AA therapy.

The standard process for manufacturing microneedles containing API requires a way to process the API, including dissolving the API in a co-solvent and a drying process. In this study, the authors introduce a novel microneedle system that involves physically attaching API particles to the biocompatible adhesive surface of the microneedles. To manufacture particle-attached microneedles, an adhesive surface was prepared by coating polydimethylsiloxane (PDMS) mixed with an elastomer base and a curing agent at a ratio of 40:1 (PDMS40) onto polylactic acid microneedles (PLA), and then attaching ovalbumin (OVA) particles with a mean diameter of 10 μm to the PDMS adhesive layer. The OVA particles were delivered for 5 min into porcine skin with a delivery efficiency of 93% ex vivo and into mouse skin with a delivery efficiency of over 90% in vivo. Finally, mouse experiments with OVA particle-attached microneedles showed a value of OVA antibody titer similar to that produced by intramuscular administration. Particle-attached microneedles are a novel microneedle system with a dry coating process and rapid API delivery into the skin. Particle-attached microneedles can provide a wide range of applications for administering drugs and vaccines.

Teriparatide is an effective drug for the treatment of osteoporosis. This study examines the relationship between the drug delivery properties of the solid formulation with teriparatide and the pharmacokinetic properties of teriparatide in vivo.

Teriparatide microneedles with different dissolution rates were prepared using sucrose and carboxymethylcellulose (CMC). There were three aspects of this study: (1) The dissolution rate of teriparatide from both formulations (sucrose and CMC) was measured in vitro. (2) After administration into porcine skin ex vivo, the diffusion rate of FITC-dextran was observed using a confocal microscope. (3) Pharmacokinetic studies were performed in rats and pharmacokinetic data compared with the release rate and the diffusion pattern.

In the in vitro dissolution experiment, 80% of teriparatide was released within 30 min from the CMC MNs, whereas 80% of teriparatide was released within 10 min from the sucrose MNs. After 30 min, the fluorescence intensity on the surface of the MNs was 40% of the initial intensity for sucrose MNs and 90% for CMC MNs. In the pharmacokinetic study, the C_max values of the CMC and sucrose MNs were 868 pg/mL and 6809 pg/mL, respectively, and the AUC_last values were 6771 pg*hr/mL for the CMC MNs and 17,171 pg*hr/mL for the sucrose MNs.

When teriparatide is delivered into the skin using microneedles, the release rate from the solid formulation determines the drug's pharmacokinetic properties. The diffusion pattern of fluorescence into the skin can be used to anticipate the pharmacokinetic properties of the drug.