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Development of Methotrexate and Minocycline-Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis

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A Correction to this article was published on 19 February 2020

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Abstract

Rheumatoid arthritis is an autoimmune disease that leads to cartilage destruction, synovial joint inflammation, and bacterial joint/bone infections. In the present work, methotrexate and minocycline-loaded nanoparticles (MMNPs) were developed with an aim to provide relief from inflammation and disease progression/joints stiffness and to control the bacterial infections associated with rheumatoid arthritis. MMNPs were developed and optimized by solvent evaporation along with high-pressure homogenization technique using poly(lactic-co-glycolic acid) (50:50%) copolymer. FTIR spectrometric results showed the compatibility nature of methotrexate, minocycline, and poly(lactic-co-glycolic acid). The MMNPs showed particle size ranging from 125.03 ± 9.82 to 251.5 ± 6.23 nm with charge of around − 6.90 ± 0.8 to − 34.8 ± 4.3 mV. The in vitro release studies showed a sustained release pattern with 75.11% of methotrexate (MTX) release and 49.11% of minocycline hydrochloride (MNC) release at 10 h. The developed MMNPs were found to be stable at refrigerated condition and non-hemolytic nature (< 22.0%). MMNPs showed superior cytotoxicity for studied concentrations (0.1 to 1000 μM) compared with free MTX at both 24 and 48 h treatment period in a dose/time-dependent manner in inflammatory RAW 264.7 cells. Anti-bacterial studies indicate that the efficacy of the developed MMNPs to control infections was compared with pure MNC. In vivo anti-arthritis showed effective arthritis reduction potential of the developed MMNPs upon intravenous administration. This proof of concept implies that MTX with MNC combined nanoparticles may be effective to treat RA associated with severe infections.

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Acknowledgments

The authors gratefully acknowledge the support received from the Department of Science and Technology (DST) (GoI), New Delhi, the National Facility for Drug Development for Academia, Pharmaceutical and Allied Industries (NFDD) (Ref No. VI- D&P/349/10-11/TDT/1 Dt: 21.10.2010), and DST, New Delhi supported National Facility for Bioactive Peptides from Milk (NFBP) Project (Ref No. VI-D&P/545/2016-17/TDT; Dt: 28.02.2017). The authors gratefully acknowledge DSC instrumentation facility acquired through Defence Research and Development Organization supported project (Ref No. ERIP/ER/1403185/M/01 /1627 Dt: 29.07.2016). The financial support (Senior Research Fellowship) received from the Indian Council of Medical Research, New Delhi (Ref No. 45/21/2018/NAN/BMS. Dt.05.06.2018) is gratefully acknowledged by one of the authors, Mr. J. Kumar.

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Authors and Affiliations

  1. Centre for Excellence in Nanobio Translational REsearch (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University, BIT Campus, Tiruchirappalli, Tamil Nadu, 620024, India

    Kumar Janakiraman, Venkateshwaran Krishnaswami, Vaidevi Sethuraman, Subramanian Natesan, Vijaya Rajendran & Ruckmani Kandasamy

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  1. Kumar Janakiraman
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  2. Venkateshwaran Krishnaswami
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  3. Vaidevi Sethuraman
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Correspondence to Vijaya Rajendran or Ruckmani Kandasamy.

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Janakiraman, K., Krishnaswami, V., Sethuraman, V. et al. Development of Methotrexate and Minocycline-Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis. AAPS PharmSciTech 21, 34 (2020). https://doi.org/10.1208/s12249-019-1581-y

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