Potensi Thioridazine Terenkapsulasi Nanopartikel Poly (Lactic-Co-Glycolic) Acid (PLGA) sebagai Inovasi Terapi Baru dalam Tatalaksana TB Resisten Obat

Authors

  • Steven Johanes Adrian Fakultas Kedokteran dan Ilmu Kesehatan Universitas Katolik Indonesia Atma Jaya, Jakarta, Indonesia
  • Tommy Fakultas Kedokteran dan Ilmu Kesehatan Universitas Katolik Indonesia Atma Jaya, Jakarta, Indonesia

DOI:

https://doi.org/10.55175/cdk.v46i11.411

Keywords:

Nanopartikel, poly (lactic-co-glycolic) acid, TB Resisten obat, thioridazine, tuberkulosis

Abstract

Tuberkulosis (TB) adalah penyakit infeksi dengan tingkat kematian tertinggi kedua secara global. Sebanyak 1,4 juta kematian terjadi pada tahun 2015. TB-Multi Drugs Resistance (TB-MDR) menyebabkan 200.000 kematian. Prevalensi TB resisten obat yang tinggi membutuhkan tatalaksana baru yang efektif dan efisien. Penggunaan thioridazine pada penderita TB resisten obat memberikan perbaikan dan dapat ditoleransi dengan baik. Thioridazine menghambat ekspresi berlebihan pompa efflux pada sel, sehingga obat-obatan TB yang sebelumnya telah resisten dapat bekerja kembali. Teknologi nanopartikel dapat digunakan untuk membawa obat sehingga lebih efektif dan efisien. Poly (lactic-co-glycolic) acid (PLGA) adalah salah satu nanopartikel yang telah disetujui oleh Food and Drug Administration (FDA). Penelitian menggunakan model larva zebrafish menunjukkan penggunaan thioridazine terenkapsulasi PLGA meningkatkan kemampuan rifampicin dalam mengeliminasi bakteri M.tuberculosis dan M.bovis sebanyak 6,3-7 kali. Penggunaan PLGA juga mengurangi efek samping dari thioridazine yang berbahaya seperti kardiotoksisitas. Thioridazine terenkapsulasi PLGA sebagai tatalaksana terhadap TB resisten obat mampu memberikan perbaikan yang signifikan terhadap subjek penelitian, sehingga dapat dijadikan sebagai terapi potensial dalam kasus TB resisten obat di Indonesia, namun dibutuhkan penelitian lebih lanjut tentang penggunaannya terutama karena masih terbatasnya studi atau penelitian klinis di Indonesia.


Tuberculosis (TB) is an infectious disease with the second highest mortality rate in the world. There were 1,4 million deaths in 2015. Multi-Drug Resistance Tuberculosis (MDR-TB) causes 200.000 deaths. High prevalence of drug resistant-TB needs a novel therapy which is effective and efficient. The use of thioridazine on drug resistant TB reduce morbidity and well tolerated. Thioridazine inhibits the excessive expression of cellular efflux pump, so the resistant TB drugs can function. Nanoparticle technology can be used to as drug carrier. Poly (lactic-co-glycolic) acid (PLGA) is one of the nanoparticle approved by Food and Drug Administration (FDA). Studies used zebrafish larva model showed the use of thioridazine encapsulated by PLGA increased the ability of rifampicin in eliminating M. tuberculosis and M. bovis 6,3-7 times. The use of PLGA also reduced the dangerous side effects of thioridazine such as cardiotoxicity. Thioridazine encapsulated by PLGA as the treatment for drugresistant can significantly improve the subject, thus it can be used as a potential treatment for drug-resistant TB. More studies about the use of the drug are needed because the studies are limited.

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References

WHO | Global tuberculosis report 2016 [Internet]. WHO. [cited 2017 Mar 28]. Available from: http://www.who.int/tb/publications/global_report/en/

Lisdawati V, Puspandari N, Rif’ati L, Soekarno T, M M, K S, et al. Molecular epidemiology study of Mycobacterium tuberculosis and its susceptibility to anti-tuberculosis drugs in Indonesia. BMC Infect Dis. 2015;15:366.

Pedoman TB Nasional 2014.pdf [Internet]. [cited 2017 Mar 24]. Available from: http://spiritia.or.id/dokumen/pedoman-tbnasional2014.pdf

WHO | World TB Day, 24 March 2017 [Internet]. WHO. [cited 2017 Mar 28]. Available from: http://www.who.int/campaigns/tb-day/2017/en/

Riskesdas 2013.pdf [Internet]. [cited 2017 Mar 24]. Available from: http://www.depkes.go.id/resources/download/general/Hasil%20Riskesdas%202013

Profil Kesehatan Indonesia 2015.pdf [Internet]. [cited 2017 Mar 24]. Available from: http://www.depkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/profil-kesehatan-Indonesia-2015.pdf

Mohan A, Kumar DP, Harikrishna J. Newer anti-TB drugs and drug delivery systems. Medicine update. New Delhi: Jaypee Brothers Medical Publishers (for The Association of Physicians of India). 2013:388-92.

Amaral L, Viveiros M. Thioridazine: A non-antibiotic drug highly effective, in combination with first line anti-tuberculosis drugs, against any form of antibiotic resistance of Mycobacterium tuberculosis due to its multi-mechanisms of action. Antibiotics. 2017;6(1):3.

Nasiruddin M, Neyaz MK, Das S. Nanotechnology-based approach in tuberculosis treatment. Tuberc Res Treat. 2017:e4920209.

Vibe CB, Fenaroli F, Pires D, Wilson SR, Bogoeva V, Kalluru R, et al. Thioridazine in PLGA nanoparticles reduces toxicity and improves rifampicin therapy against mycobacterial infection in zebrafish. Nanotoxicology. 2016;10(6):680–8.

Zhang Y, Yew W-W. Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015. Int J Tuberc Lung Dis. 2015;19(11):1276–89.

Dutta NK, Pinn ML, Karakousis PC. Reduced emergence of isoniazid resistance with concurrent use of Thioridazine against acute murine tuberculosis. Antimicrob Agents Chemother. 2014;58(7):4048–53.

Abbate E, Vescovo M, Natiello M, Cufré M, García A, Gonzalez Montaner P, et al. Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and Thioridazine. J Antimicrob Chemother. 2012;67(2):473–7.

Dutta NK, Pinn ML, Karakousis PC. Sterilizing activity of Thioridazine in combination with the first-line regimen against acute murine tuberculosis. Antimicrob Agents Chemother. 2014;58(9):5567–9.

Kishore KK, Ramakanth GSH, Chandrasekhar N, Kishan PV, Chiranjeevi UK, Usharani P. Thioridazine: A potential adjuvant in pharmacotherapy of drug resistant tuberculosis Ki. Int J Basic Clin Pharmacol. 2017;3(6):928–32.

Jawahar N, Reddy G, Nanoparticles: A novel pulmonary drug delivery system for tuberculosis. J Pharm Sci & Res. 2012:1901-1906

Danhier F, Ansorena E. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release. 2012:505-522

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Published

01-11-2019

How to Cite

Adrian, S. J., & Tommy. (2019). Potensi Thioridazine Terenkapsulasi Nanopartikel Poly (Lactic-Co-Glycolic) Acid (PLGA) sebagai Inovasi Terapi Baru dalam Tatalaksana TB Resisten Obat. Cermin Dunia Kedokteran, 46(11), 697–700. https://doi.org/10.55175/cdk.v46i11.411

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