Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study

Abstract

Conventional oral administration of antifilariasis drugs results in nonspecific targeting of the drugs and the intradermal delivery of nanoparticles with sizes of <100 nm could be used to improve lymphatic uptake. This study investigated the combination of nanosuspension and dissolving microneedles (MN-NS) as an alternative intradermal delivery approach for the delivery of antifilariasis drugs, namely doxycycline, albendazole, and ivermectin. NS were fabricated and optimized using a bottom-up technique. The NS were then incorporated into the MN arrays. The optimized NS were <100 nm in diameter. Furthermore, MN-NS had suitable mechanical strength and insertion capabilities. The dermatokinetic study revealed that the delivery of drugs into the dermis of excised neonatal porcine skin by MNs was significantly higher than that from a needle-free patch, with 29.29 ± 4.65%, 31.54 ± 5.35%, and 34.54 ± 4.98% of doxycycline, albendazole sulfoxide, and ivermectin retained in the dermis after 24 h. The results presented here serve as proof of concept for the significant enhancement of drug retention times in the dermis, following their formulation into NS and delivery via MN. Leading on from these studies, future work must investigate in vivo lymphatic pharmacokinetic profiling of drugs formulated into NS, in a suitable animal model.

Localised and sustained intradermal delivery of methotrexate using nanocrystal-loaded microneedle arrays: Potential for enhanced treatment of psoriasis

“…MTX release from its MTX NC and MTX Na solution (as a control) was evaluated in vitro using a dialysis method ( Permana et al., 2019 ). To mimic the conditions of the interstitial fluid in the skin, phosphate-buffered saline 10 mM (PBS, pH 7.4) was used as a release medium.…”

“…To determine the release model that best described the drug release kinetics, the in vitro release data was substituted into different mathematical release kinetic models, namely zero-order, first-order, Higuchi and Korsmeyer- Peppas, as outlined in previous studies ( Permana et al., 2019 ). …”

WITHDRAWN: Coated polymeric needles for rapid and deep intradermal delivery

“…Quantification of rhodamine B across the skin was evaluated by sectioning samples in 50 μm thickness using a Leica CM1900 Cryostat (Leica Microsystems, Nussloch, Germany) and collecting 10 consecutive slices into Eppendorf tubes. To analyse the amount of drug distribution across the skin, 1 mL of methanol was added to the tubes and samples were homogenised with a Tissue Lyser LT (Qiagen, Ltd., Manchester, UK) at 50 Hz for 15 min to extract the drug from the skin (Permana et al, 2019). Then, samples were centrifuged at 14,000 ×g for 15 min.…”

Montelukast Nanocrystals for Transdermal Delivery with Improved Chemical Stability

“…Drug nanocrystal suspension was fabricated using acid-neutralization method as reported previously [26,27], with slight modification. At first, drug alkaline solution (5-20 mg/mL as MTK) was prepared by dissolving sodium salt of MTK powder (62.4-249.6 mg) in 10 mM NaOH solution (4 mL, pH 12).…”

“…In this method, the weak-acid MTK compound dissolved in the alkaline solution (10 mM NaOH solution) was added dropwise to the stabilizer-containing acidic solution (10 mM lactic acid solution). The drug solubility was drastically diminished in the acidic condition, instigating a rapid drug re-crystallization process [27]. The drug nanocrystals formed by the nucleation and crystal growth process were then ultra-sonicated to decrease the crystal size and uniformly disperse the nanocrystals using steric stabilizers.…”