Factors affecting the penetration in microneedles and PLGA nanoparticle-assisted drug delivery: Importance of preparation and formulation

Abstract Purpose Oral administration of the first-line antidepressant paroxetine (PAX) has certain limitations, including difficulty in reaching the brain due to oral absorption. Although there are many invasive and non-invasive strategies available to cross the blood–brain barrier (BBB), they run counter to long-term administration and convenience for patients. Methods We herein designed a simple PAX-loaded nanoparticle-integrated dissolving microneedles system (PAX-NP-DMNs), aiming to improve the bioavailability of PAX through the synergistic permeation-enhancing effect of microneedles (MNs) and nanoparticles (NPs). Results We assessed the NPs characteristics before and after MNs preparation and confirmed the successful construction of PAX-NP-DMNs based on differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. In the mechanical strength test, the addition of NPs increased the mechanical strength of dissolving MNs by 0.43 times and prolonged the release of PAX from 1 h to 48 h; PAX-NP-DMNs has over 40 times than PAX solution in the isolated skin penetration in permeability experiments. Moreover, PAX-NP-DMNs has good biocompatibility and does not cause adverse reactions. Conclusion Loading PAX into polylactic glycolic copolymer NPs and adding them into MNs can effectively improve the bioavailability of PAX and the mechanical strength problem of dissolving MNs. PAX-NP-DMNs can easily penetrate the skin to provide rapid and painless delivery without causing adverse effects, thus offering a more convenient and effective method for the treatment of central nervous diseases.