Development of pH-Sensitive Nanoparticle Incorporated into Dissolving Microarray Patch for Selective Delivery of Methotrexate

• Published in: AAPS PharmSciTech Vol. 25; no. 4; p. 70
• Main Authors: Febrianti, Nur Qadri, Aziz, Anugerah Yaumil Ramadhani, Tunggeng, Muhamad Gilang Ramadhan, Ramadhany, Indianty Dwi, Syafika, Nur, Azis, Sumayya Binti Abd, Djabir, Yulia Yusrini, Asri, Rangga Meidianto, Permana, Andi Dian
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 27.03.2024
• Subjects: Animals; Arthritis, Rheumatoid - drug therapy; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chickens; Drug Carriers - therapeutic use; Female; Hemolysis; Humans; Hydrogen-Ion Concentration; Methotrexate; Nanoparticles; Pharmacology/Toxicology; Pharmacy; Research Article; methotrexate; pH-sensitive nanoparticle; rheumatoid arthritis; targeting delivery; dissolving microarray patch
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-024-02777-y

Purpose Rheumatoid arthritis (RA) is a systemic autoimmune disease that attacks human joints. Methotrexate (MTX), as one the most effective medications to treat RA, has limitations when administered either orally or by injection. To overcome this limitation, we formulated MTX through a smart nanoparticle (SNP) combined with dissolving microarray patch (DMAP) to achieve selective-targeted delivery of RA. Methods SNP was made using the combination of polyethylene glycol (PEG) and polycaprolactone (PCL) polymers, while DMAP was made using the combination of hyaluronic acid and polyvinylpyrrolidone K-30. SNP-DMAP was then evaluated for its mechanical and chemical characteristics, ex vivo permeation test, in vivo pharmacokinetic study, hemolysis, and hen’s egg test-chorioallantoic membrane (HET-CAM) test. Result The results showed that the characteristics of the SNP-DMAP-MTX formulas meet the requirements for transdermal delivery, with the particle size of 189.09 ±12.30 nm and absorption efficiency of 65.40 ± 5.0%. The hemolysis and HET-CAM testing indicate that this formula was non-toxic and non-irritating. Ex vivo permeation shows a concentration of 51.50 ± 3.20 µg/mL of SNP-DMAP-MTX in PBS pH 5.0. The pharmacokinetic profile of SNP-DMAP-MTX showed selectivity and sustained release compared with oral and DMAP-MTX with values of t 1/2 (4.88 ± 0 h), Tmax (8 ± 0 h), Cmax (0.50 ± 0.04 μg/mL), AUC (3.15 ± 0.54 μg/mL.h), and mean residence time (MRT) (9.13 ± 0 h). Conclusion The developed SNP-DMAP-MTX has been proven to deliver MTX transdermal and selectively at the RA site, potentially avoiding conventional MTX side effects and enhancing the effectiveness of RA therapy. Graphical Abstract