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

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Abstract

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 t1/2 (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.

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Data Availability

All data generated or analyzed during this study are included in this published article.

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Funding

The author is grateful to the Program Kreativitas Mahasiswa (PKM), Directorate General of Higher Education, Ministry of Education and Culture of the Republic of Indonesia for their support.

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Authors and Affiliations

  1. Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia

    Nur Qadri Febrianti, Anugerah Yaumil Ramadhani Aziz, Muhamad Gilang Ramadhan Tunggeng, Indianty Dwi Ramadhany, Nur Syafika, Sumayya Binti Abd Azis, Yulia Yusrini Djabir, Rangga Meidianto Asri & Andi Dian Permana

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  1. Nur Qadri Febrianti
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  2. Anugerah Yaumil Ramadhani Aziz
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Contributions

N.Q.F.: conceptualization, methodology, and writing the manuscript. A.Y.R.A.: methodology and writing the manuscript. M.G.R.T.: methodology and writing the manuscript. I.D.R.: methodology and writing the manuscript. N.S.: methodology and writing the manuscript. S.B.A.A.: data curation and validation. Y.Y.D.: data curation and validation. R.M.A.: data curation and validation. A.D.P.: conceptualized, reviewed, finalized, funding acquisition, edited the manuscript and supervision.

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Febrianti, N.Q., Aziz, A.Y.R., Tunggeng, M.G.R. et al. Development of pH-Sensitive Nanoparticle Incorporated into Dissolving Microarray Patch for Selective Delivery of Methotrexate. AAPS PharmSciTech 25, 70 (2024). https://doi.org/10.1208/s12249-024-02777-y

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