Potensi Polimer Poly-Lactic-co-Glicolyc Acid untuk Terapi Kanker dan Perkembangan Uji Kliniknya
Abstract
Penyakit kanker merupakan salah satu penyebab kematian utama di seluruh dunia. Pada tahun 2012, kanker menjadi penyebab kematian sekitar 8,2 juta orang. Poly-Lactic-co-Glicolyc Acid (PLGA) merupakan salah satu polimer yang mampu terurai secara biologis (biodegradable) yang sering digunakan sebagai nanokarier yang efektif untuk penghantaran obat ke dalam sel. PLGA bersifat biodegradable karena diuraikan menjadi senyawa endogen yaitu asam laktat dan asam glikolat dan mudah dimetabolisme oleh tubuh melalui siklus Krebs sehingga memiliki sifat toksisitas sistemik yang rendah serta telah disetujui Food and Drug Administration (FDA) untuk terapi pada manusia. Banyak obat antikanker yang dienkapsulasi menggunakan PLGA dan telah dilakukan uji in vitro, in vivo dan uji klinik. Artikel review ini bertujuan untuk mengetahui potensi PLGA untuk terapi kanker dan perkembangan uji kliniknya saat ini. Metode penulisan artikel review ini dilakukan melalui penelusuran pustaka. Hasil review dari 38 artikel menunjukkan bahwa polimer PLGA sangat berpotensi dalam penghantaran obat antikanker baik secara pasif maupun aktif. Beberapa produk sedang berada dalam tahap uji in vitro, in vivo dan klinik. Namun, produk yang telah beredar di pasaran menunjukkan bahwa PLGA terbukti berpotensi dan aman sebagai polimer untuk menghantarkan obat ke sel kanker prostat.
Kata kunci: PLGA, uji klinik, polimer, biodegradable, kanker
Biodegradable Polymer Potential of Poly-Lactic-co-Glicolyc Acid for Cancer Therapy and Its Clinical Trial
Cancer is one of the leading causes of death worldwide. In 2012, cancer causes death of about 8.2 million people. Poly-Lactic-co-Glicolyc Acid (PLGA) is one of the biodegradable polymers that is often used as an effective nanocarrier for drug delivery into cells. PLGA is biodegradable because it is decomposed into endogenous compounds namely lactic acid and glycolic acid and easily metabolized by the body through the Krebs cycle, so it has low systemic toxicity properties and has been approved by Food and Drug Administration (FDA) for human therapy. Many anticancer drugs are encapsulated using PLGA and have been tested in vitro, in vivo and clinical trial. This review article aimed to determine the potential of PLGA for cancer therapy and the development of current clinical trials. Data in this review article is obtained from library search. The review result of 38 articles indicate that the PLGA polymer is highly potential in delivering anticancer drugs either passively or actively. Some products are undergoing in vitro test, in vivo test, and clinical trials. However, marketed products show that PLGA is proven to be potential and safe as a polymer to deliver drugs into prostate cancer cells.
Keywords: PLGA, clinical study, polymer, biodegradable, cancer
Keywords
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Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality wordlwide: Sources, methods, and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5):E359–86. doi: 10.1002/ijc.29210
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. Cancer J Clin. 2018;68(1): 7–30. doi: 10.3322/caac.21442
Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release. 2012; 161 (2):505–22. doi: 10.1016/j.jconrel.2012.01.043.
Hillaireau H, Couvreur P. Nanocarriers’ entry into the cell: Relevance to drug delivery. Cell Mol Life Sci. 2009;66(17): 2873–96. doi: 10.1007/s00018-009-0053-z
Peres C, Matol AL, Conniot J, Sainz V, Zupancic E, Silva JM, et al. Poly (lactic acid)-based particulate systems are promising tools for immune modulation. Acta Biomater. 2017;48:41–57. doi: 10.1016/j.actbio.2016.11.012.
Locatelli E, Franchini MC. Biodegradable PLGA-b-PEG polymeric nanoparticles: Synthesis, properties, and nanomedical applications as drug delivery system. J Nanoparticle Res. 2012;14(12):1–17. doi: 10.1007/s11051-012-1316-4.
Ratzinger G, Agrawal P, Körner W, Lonkai J, Sanders HM, Terreno E, et al. Surface modification of PLGA nanospheres with Gd-DTPA and Gd-DOTA for high-relaxivity MRI contrast agents. Biomaterials. 2010;31(33):8716–23. doi: 10.1016/j.biomaterials.2010.07.095.
Mir M, Ahmed N, Rehman AU. Recent applications of PLGA based nanostructures in drug delivery. Colloids Surf B Biointerfaces. 2017;159:217–31. doi: 10.1016/j.colsurfb.2017.07.038
Danhier F, Lecouturier N, Vroman B, Jerome C, Marchand-Brynaert J, Feron O, et al. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation. J Control Release. 2009;133(1):11–7. doi: 10.1016/j.jconrel.2008.09.086
Derakhshandeh K, Erfan M, Dadashzadeh S. Encapsulation of 9-nitrocamptothecin, a novel anticancer drug, in biodegradable nanoparticles: Factorial design, characterization and release kinetics. Eur J Pharm Biopharm. 2007;66(1):34–41. doi: 10.1016/j.ejpb.2006.09.004
Choi SH, Park TG. G-CSF loaded biodegradable PLGA nanoparticles prepared by a single oil-in-water emulsion method. Int J Pharm. 2006;311(1–2):223–8. doi: 10.1016/j.ijpharm.2005.12.023
Luo G, Jin C, Long J, Fu D, Yang F, Xu J, et al. RNA interference of MBD1 in BxPC-3 human pancreatic cancer cells delivered by PLGA-poloxamer nanoparticles. Cancer Biol Ther. 2009;8(7):594–8. doi: 10.4161/cbt.8.7.7790
Braden AR, Kafka MT, Cunningham L, Jones H, Vishwanatha JK. Polymeric nanoparticles for sustained down-regulation of annexin A2 inhibit prostate tumor growth. J Nanosci Nanotechnol. 2009;9(5):2856–65. doi: 10.1166/jnn.2009.028
Chittasupho C, Xie SX, Baoum A, Yakovleva T, Siahaan TJ, Berkland CJ. ICAM-1 targeting of doxorubicin-loaded PLGA nanoparticles to lung epithelial cells. Eur J Pharm Sci. 2009;37(2):141–50. doi: 10.1016/j.ejps.2009.02.008
Liang C, Yang Y, Ling Y, Huang Y, Li T, Li X. Improved therapeutic effect of folate-decorated PLGA-PEG nanoparticles for endometrial carcinoma. Bioorg Med Chem. 2011;19(13):4057–66. doi: 10.1016/j.bmc.2011.05.016
Luo G, Yu X, Jin C, Yang F, Fu D, Long J, et al. LyP-1-conjugated nanoparticles for targeting drug delivery to lymphatic metastatic tumors. Int J Pharm. 2010; 385(1–2):150–6. doi: 10.1016/j.ijpharm.2009.10.014
Dhar S, Gu FX, Langer R, Farokhzad OC, Lippard SJ. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGAPEG nanoparticles. Proc Natl Acad Sci U. S. A. 2008:105(45)17356–61. doi 10.1073/pnas.0809154105
Danhier F, Vroman B, Lecouturier N, Crokart N, Pourcelle V, Freichels H, et al. Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with paclitaxel. J Control Release 2009;140(2):166–73. doi: 10.1016/j.jconrel.2009.08.011
Guo J, Gao X, Su L, Xia H, Gu G, Pang Z, et al. Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials. 2011; 32(31):8010–20. doi: 10.1016/j.biomaterials.2011.07.004
Chen, H Gao J, Lu Y, Kou G, Zhang H, Fan L, et al. Preparation and characterization of PE38KDEL-loaded anti-HER2 nanoparticles for targeted cancer therapy. J Control Release. 2008;128(3):209–16. doi: 10.1016/j.jconrel.2008.03.010
FDA. Lupron depot® [Accessed on: 4th December 2017]. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020011s040lbl.pdf
Malik K, Singh I, Nagpal M, Arora S. Atrigel: A potential parenteral controlled drug delivery system. Der Pharm Sin. 2010;1(1):74–81.
Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185–98. doi: 10.1146/annurev-med-040210-162544
Prabhakar U, Maeda H, Jain RK, Eva M, Sevick-muraca, Zamboni W, et al. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res. 2013;73(8):2412–7. doi: 10.1158/0008-5472.CAN-12-4561
Guo S, Huang L. Nanoparticles containing insoluble drug for cancer therapy. Biotechnol Adv. 2014;32(4):778–88. doi: 10.1016/j.biotechadv.2013.10.002
Wolinsky JB, Colson YL, Grinstaff MW. Local drug delivery strategies forcancer treatment: gels, nanoparticles, polymeric films, rods, and wafers. J Control Release 2012;159(1):14–26. doi: 10.1016/j.jconrel.2011.11.031
Prokop A, Davidson JM. Nanovehicular intracellular delivery systems. J Pharm Sci. 2008;97(9):3518–90. doi: 10.1002/jps.21270
Vert M, Mauduit J, Li S. Biodegradation of PLA/GA polymers: Increasing complexity. Biomaterials. 1994;15(15):1209–13. doi: 10.1016/0142-9612(94)90271-2
Alshamsan A. Nanoprecipitation is more efficient than emulsion solvent evaporation method to encapsulate cucurbitacin I in PLGA nanoparticle. Saudi Pharm J. 2014; 22(3):219–22. doi: 10.1016/j.jsps.2013.12.002
Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75(1):1–18. doi: 10.1016/j.colsurfb.2009.09.001
Vasir JK, Labhasetwar V. Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev. 2007;59:718–28. doi: 10.1016/j.addr.2007.06.003
Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011;63(3):170–83. doi: 10.1016/j.addr.2010.10.008
Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46:6387 –92.
Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135–46. doi: 10.1016/j.jconrel.2010.08.027
Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med. 1971;285(21):1182–6. doi: 10.1056/NEJM197111182852108
Wohlfart S, Khalansky AS, Gelperina S, Maksimenko O, Bernreuther C, Glatzel M, et al. Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers. PLoS One. 2011;6(5):e19121. doi: 10.1371/journal.pone.0019121.
Fonseca C, Simoes S, Gaspar R. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Control Release. 2002;83(2):273–86.
Zhang Z, L.S. Huey LS, Feng SS. Folate-decorated poly(lactide-co-glycolide)-vitamin E TPGS nanoparticles for targeted drug delivery. Biomaterials. 2007;28(10):1889–99. doi: 10.1016/j.bio materials.2006.12.018
DOI: https://doi.org/10.15416/ijcp.2018.7.1.59
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