Aptamer as a Targeted Drug Delivery

  • Sadar Mayur Devsing Mayur DevsingSadar. Department of Pharmacy, PRMS’s Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.
  • Rahul Sarode Prof. Rahul JagdevSarode. Department of Pharmacy, Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.
  • Saloni Khandelwal Saloni ShitalKhandelwal. Department of Pharmacy, Anuradha College of Pharmacy, Chikhli,Dist-Buldhana,Maharashtra, India.
  • Kailash R Biyani Department of Pharmacy, Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.

Abstract

Aptamers are the synthetic oligonucleotides which are short single-stranded in nature with having three-dimensional shape or structure. From the past few years, Aptamers as inventive targeting molecules play an important role in the biomedical field. Aptamers are generated by the method termed as SELEX. Aptamers have a unique feature in which they bind to the desired targets or the receptors on the cell membrane utilizing their high affinity and specificity. So, for drug delivery as targeting ligands, aptamers can be provided. In the research field, for monitoring the environment and ensure the food safety aptamers are generally used. They also used as a therapeutic agent and plays an important role in clinical diagnosis. An Aptamer is a fascinating tool that is mainly used in molecular biology applications, as well as potential pharmaceutical agents and the reason behind this fascinating tool, is the various unique properties of the aptamer. Aptamers have more advantages over antibodies. They can be selected against bacteria and viruses. This review provides an overview of the development of Cell-Specific aptamers for targeted drugs along with the advantages, uses, and applications of aptamers.


 

Keywords: Aptamer, SELEX, Targeted Drug Delivery, Antibodies, Cell-specific.

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Author Biographies

Sadar Mayur Devsing, Mayur DevsingSadar. Department of Pharmacy, PRMS’s Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.

Mayur DevsingSadar. Department of Pharmacy, PRMS’s Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.

Rahul Sarode, Prof. Rahul JagdevSarode. Department of Pharmacy, Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.

Prof. Rahul JagdevSarode. Department of Pharmacy, Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.

Saloni Khandelwal, Saloni ShitalKhandelwal. Department of Pharmacy, Anuradha College of Pharmacy, Chikhli,Dist-Buldhana,Maharashtra, India.

Saloni ShitalKhandelwal. Department of Pharmacy, Anuradha College of Pharmacy, Chikhli,Dist-Buldhana,Maharashtra, India.

Kailash R Biyani, Department of Pharmacy, Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.

Department of Pharmacy, Anuradha College of Pharmacy, Chikhli, Dist-Buldhana, Maharashtra, India.

References

1. Tuerk,C;Gold,L.Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990; 249,505-510.
2. Ellington,A.D.;Szostak, J.W. In vitro selection of RNA molecules that bind specific ligands. Nature 1990; 346,818-822.
3. ZhenjianZhuo, Yuanyuan Yu, Maolin Wang, Zongkang Zhang, Jin Liu, Xiaohao Wu, Aiping Lu, Ge Zhang, Baoting Zhang. Recent Advances in SELEX Technology and Aptamer Applications in Biomedicine. Int. J. Mol. Sci. 2017; 18:2142; doi:10.3390/ijms18102142
4. Hicke, B.J., and Stephens, A.W. (2000). Escort aptamers: a delivery service for diagnosis and therapy. J. Clin. Invest. 106,923-928.
5. Jiehua Zhou and John J. Rossi. Cell-Specific Aptamer-Mediated Targeted Drug Delivery. Oligonucleotides. 2011; 21(1):1-10; doi:10.1089/oli.2010.0264
6. Conrad RC et.al. In vitro selection of nucleic acid aptamers that bind proteins. Combinatorial Chemistry. 1996; 267:336-367.
7. Vater A, Kleussmann S. Toward third generation aptamers: Spiegelmers and their therapeutic prospects. Current Opinion in Drug Discovery and Development. 2003; 6(2):253-261.
8. Hamm J. Characterisation of antibody-binding RNAs selected from structurally constrained libraries. Nucleic acid Research. 1996; 24(12):2220-2227.
9. Mohammad Gayoor khan, UmamaYezdani, Aartisinghkushwah. Case study on multiple tuberculomas, Pott's Spine with Pulmonary Koch's. JOCRIMS,5(1):16-20,2019
10. Wang C et.al. Strategies for combination of Aptamer and targeted drug delivery. Journal of Nanoscience and Nanotechnology. 2014; 14(1):501-512.
11. Joyce GF. In Vitro evolution of nucleic acids. Current Opinion in Structural Biology. 1994; 4(3):331-336.
12. Gopinath SCB. Methods developed for SELEX. Analytical and bioanalytical Chemistry. 2007; 387(1):171-182.
13. Mendonsa S.D, Bowser M.T. In Vitro evolution of functional DNA using capillary electrophoresis. J. Am. Chem. Soc. 2004; 126:20-21.
14. Mendonsa S.D., Bowser M.T. In vitro selection of high affinity DNA ligands for human ige using capillary electrophoresis. Anal. Chem. 2004; 76:5387-5392.
15. Daniels D.A., Chen H., Hicke B.J., Swiderek K.M., Gold L. A tenascin-c Aptamer identified by tumour cell selex: Systematic evolution of ligands by exponential enrichment. Proc. Natl. Acad. Sci. USA. 2003; 100:15416-15421.
16. Hicke B.J., Martin C., Chan Y.F., Gould T., Lynott C.K., Parma D., Schmidt P.G., Warren S. Tenascin-C aptamers are generated using tumour cells and purified protein. J. Biol. Chem. 2001; 276:48644-48654.
17. Phillips JA., Lopez-Colon D, Zhu Z, Xu Y, Tan W. Applications of aptamers in cancer cell biology. Anal. Chim. Acta. 2008; 621:101-108.
18. Fang X., Tan W. Aptamers generated from Cell SELEX for molecular medicine: a chemical biology approach. Acc. Chem. Res. 2010;43(1):48-57: doi: 10.1021/ar900101s.
19. Gold L, Brody E , Heilig J, Singer B. One, two, infinity: genomes filled with aptamers. Chem Biol. 2002; 9(12):1259-64.
20. Matsugami A, et.al. Structural basis of the highly efficient trapping of the HIV Tat protein by an RNA Aptamer. Structure. 2003; 11(5):533
21. AnnamariaRuscito and Maria C. DeRosa. Small Molecule Binding Aptamers: Selection Strategies, characterization, and Applications. Front. Chem. 2016; 4:14.
22. Vinkenborg JL , Karnowski N , Famulok M. Aptamers for allosteric regulation. Nat. Chem. Biol. 2011;7(8):519-27: doi: 10.1038/nchembio.609.
23. Li Xu , Zhen Zhang , Zilong Zhao , Qiaoling Liu , Weihong Tan , Xiaohong Fang. Cellular Internalization and Cytotoxicity of Aptamers Selected from Lung Cancer Cell. Am. J. Biomed. Sci. 2013; 5(1):47-58: doi: 10.5099/aj130100047.
24. Hongguang Sun, Xun Zhu, Patrick Y Lu, Roberto R Rosato , Wen Tan , and YouliZu. Oligonucleotides Aptamers: New Tools for Targeted Cancer Therapy. Mol. Ther. Nucleic Acids. 2014; 3(8):e182.
25. Zhang Y., et.al. Tumour Targeted Drug Delivery with Aptamers. Curr. Med. Chem. 2011; 18(27):4185-94.
26. Mohd. Gayoor Khan. The Novel Drug Delivery System. World J Pharm Pharm Sci., 2017; 6(7):477-487.
27. Dr. H.S Chandel., Sharad P. Panday, Arvind Dangi, Ashish chaurasia, Mohd.Gayoor khan et al. Development of Targeted Drug Delivery. International Journal of research methodology Ijrm. Human., 2017; 1(2):30-34.
28. A. Davydova et al. Aptamers against pathogenic microorganisms. Crit Rev Microbiol. 2016; 42(6):847-865
29. Cheng Wang, Biao Liu, Jun Lu , Ge Zhang , and Aiping Lu. Strategies for combination of Aptamer and Targeted Drug Delivery. J. Nanosci. Nanotechnol. 2014; 14:501-512: doi: 10.1166/jnn.2014.8746.
30. MuslumIlgu, RezzanFazlioglu, MericOzturk, YaseminOzsurekci and Marit Nilsen-Hamiltonn (April 10th 2019). Aptamers for Diagnostics with applications for Infectious Diseases, Recent Advances in Analytical Chemistry, MuharremInce and Olcay Kaplan Ince, Intech Open, DOI: 10.5772/intechopen.84867.
31. Lee KH, Zeng H. Aptamer based ELISA assay for highly specific and sensitive detection of Zika NS1 protein. Analytical Chemistry. 2017; 89(23):12743-12748: doi: 10.1021/acs.analchem.7b02862.
32. Kwon HM, Lee KH, Han BW, Han MR, Kim DE. An RNA Aptamer that specifically binds to to the glycosylated hemagglutinin of avian influenza virus and suppresses viral infection in cells. PLOS One. 2014; 9(5):e97574.
33. Liu J., Yang Y, Hu B, Ma ZY, Huang HP, Yu Y, et.al. Development of HBsAg-binding aptamers that bind HepG2.2.15 cells via HBV surface antigen. VirologicaSinica. 2010; 25(1):27-35.
34. Tombelli S, Minunni M, Luzi E, Mascini M. Aptamer-based biosensors for the detection of HIV-1 Tat protein. Bioelectrochemistry. 2005; 67(2):135-141.
35. Minuni M, Tombelli S, Gullotto A, Luzi E, Mascini M. Development of biosensors with aptamers as bio-recognition element: The case of HIV-1 Tat protein. Biosensors and Bioelectronics. 2004; 20(6):1149-1156.
36. Zhang Y, Yu Z, Jiang F, Fu P, Shen J, Wu W, et al. Two DNA aptamers against avian influenza H9N2 virus prevent viral infection in cells l. PLos One. 2015; 10(3):e0123060: doi: 10.1371/journal.pone.0123060.
37. Lai HC, Wang CH, Liou TM, Bin LG. Influenza A virus-specific aptamers screened by using an integrated Microfluidic system l. Lab on a Chip. 2014; 14(12):2002-2013.
38. Rahim Ruslinda A, Tanabe K, Ibori S, Wang X, Kawarada H. Effects of diamond-FET-based RNA aptamer sensing for detection of real sample of HIV-1 Tat protein. Biosensors and Bioelectronics. 2013; 40(1):277-282.
39. Zhou J, Swiderski P, Li H, Zhang J, Neff CP, Akkina R, et al. Selection, characterisation and application of new RNA HIV gp 120 aptamers for facile delivery of Dicer substrate siRNAs into HIV infected cells. Nucleic Acids Research. 2009; 37(9):3094-3109. DOI: 10.1093/nar/gkp185.
40. Turek C, MacDougal S, Gold L. RNA pseudoknots that inhibit human immunodeficiency virus type 1 reverse transcriptase. Proceedings of the National Academy of Sciences of the United States of America. 1992; 89(15):6988-6992.
41. Somasunderam A, Ferguson MR, Rojo DR, Thiviyanathan V, Li X, O'Brien WA, et al. Combinatorial selection, inhibition, and antiviral activity of DNA thioaptamers targeting the RNase H domain of HIV-1 reverse transcriptase. Biochemistry. 2005; 44(30):10388-10395.
42. Kumar PKR, Machida K, Urvil PT, Kakiuchi N, Vishnuvardhan D, Shimotohno K, et al. Isolation of RNA aptamers specific to the NS3 protein of hepatitis C virus from a pool of completely random RNA. Virology. 1997; 237(2):270-282. DOI: 10.1006/viro.1997.8773.
43. Bellecave P, Andreola M-L, Ventura M, Tarrago-Litvak L, Litvak S, Astier-Gin T. Selection of DNA aptamers that bind the RNA-dependent RNA polymerase of hepatitis C virus and inhibit viral RNA synthesis in vitro. Oligonucleotides. 2003; 13(6):455-463. DOI: 10.1089/154545703322860771.
44. Bellecave P, Cazenave C, Rumi J, Staedel C, Cosnefroy O, Andreola ML, et al. Inhibition of hepatitis C virus(HCV) RNA Polymerase by DNA aptamers: Mechanism of inhibition of in vitro RNA synthesis and effect on HCV-infected cells. Antimicrobial Agents and Chemotherapy. 2008; 52(6):2097-2110.
45. Lee SH, Ahn JY, Lee KA, Um HJ, Sekhon SS, Sun Park T, et al. Analytical bioconjugates, aptamers, enable specific quantitative detection of Listeria monocytogenes. Biosensors and Bioelectronics. 2015; 68:272-280.
46. Nishikawa F, Funaji K, Fukuda K, Nishikawa S. In vitro selection of RNA aptamers against the HCVNS3 helicase domain. Oligonucleotides. 2004; 14:114.
47. Shi S, Yu X, Gao Y, Xue B, Wu X, Wang X, et al. Inhibition of hepatitis C virus production by aptamers against the core protein. Journal of virology. 2015; 88(4):1990-1999.
48. Yuan S, Zhang N, Singh K, Shuai H, Chu H, Zhou J, et al. Cross-protection of influenza A virus infection by a DNA aptamer targeting the PA endonuclease domain. Antimicrobial Agents and Chemotherapy. 2015; 5 9(7):4082-4093.
49. Belyaeva T, Nicol C, Cesur O, Trave G, Blair G, Stonehouse N. An RNA Aptamer targets the PDZ-binding motif of the HPV16 E6 oncoprotein. Cancers (Basel). 2014; 6(3):1553-1569. DOI: 10.3390/cancers6031553.
50. Shubham S, Hoinka J, Banerjee S, Swanson E, Dillard JA, Lennemann NJ, et al. A 2’FY-RNA motif defines an Aptmaer for Ebolavirus secreted protein. Science Reports. 2018; 8(1):12373. DOI: 10.1038/s41598-018-30590-8.
51. Suenaga E, Kumar PKR. An aptamer that binds efficiently to the hemagglutinins of highly pathogenic avian influenza viruses ( H5N1 and H7N7 ) and inhibits hemagglutinin-glycan interactions. ActaBiomaterialia. 2014; 10(3):1314-1323. DOI: 10.1016/j.actbio.2013.12.034.
52. Mohd. Gayoor Khan, NileshKushwaha, Fazal Khan, Vipul Patel. Microencapsulation. International journal of research methodology Ijrm. Human., 2017; 1(2):35-42.
53. YezdaniUmama, Venkatajah G, RavShourabh, Roshan Kumar, Arvind Verma, Ayush Kumar, Md. Khan Gayoor et al. The scenario of pharmaceuticals and development of microwave assisted extraction technique. World J Pharm Pharm Sci., 2019; 8(7):1260-1271.
54. Mohd. Gayoor khan et al. Radiopharmaceuticals Drug interactions. IJCRP. 2017; 1(5):40-47.
55. KushwahNilesh, YezdaniUmama , Mohammad Gayoor khan, Manish Kushwah, Kumar Ayush. The fundamental of Novel Drug Delivery System: Methodology, Role of Nanotechnology; Nanoparticles in Pharmaceutical Research. International Journal Of Emerging Technologies and Innovative Research. ISSN:2349-5162, June-2019; 6(6):140-146. DOI: http://doi.one/10.1729/Journal.21510.
56. Chen HL, Hsiao WH, Lee HC, Wu SC, Cheng JW. Selection and characterization of DNA aptamers targeting all four serotypes of dengue viruses. PLoS One. 2015; 10(6):e0131240. DOI: 10.1371/journal.pone.0131240.
57. Choi SK, Lee C, Lee KS, Choe SY, Mo IP, Seong RH, et al. DNA aptamers against the receptor binding region of hemagglutinin prevent avian influenza viral infection. Molecules and Cells. 2011; 32(6):527-533. DOI: 10.1007/s10059-011-0156x.
58. Misono TS, Kumar PKR. Selection of RNA aptamers against human influenza virus hemagglutinin using surface plasmon resonance. Analytical Biochemistry. 2005; 342(2):312-317.
59. Sung HJ, Kayhan B, Ben-Yedidia T, Arnon R. A DNA aptamer prevents influenza infection by blocking the receptor binding region of the viral hemagglutinin. The Journal of Biological Chemistry. 2004; 279(46):48410-48419.
60. Gopinath SCB, Misono TS, Kawasaki K, Mizuno T, Imak M, Odagiri T, et al. An RNA Aptamer that distinguishes between closely related human influenza viruses and inhibits haemagglutinin-mediated membrane fusion. The Journal of General Virology. 2006; 87(3):479-487.
61. Shum KT, Tanner JA. Differential inhibitory activities and stabilisation of DNA aptamers against the SARS coronavirus helicase. Chembiochem. 2008; 9(18):3037-3045.
62. Yang M, Peng Z, Ning Y, Chen Y, Zhou Q, Deng L. Highly specific and cost-efficient detection of Salmonella Paratyphi A combining aptamers with single – walled carbon nanotubes. Sensors (Switzerland). 2013; 13(5):6865-6881.
63. Huang Y, Chen X, Duan N, Wu S, Wang Z, Wei X, et al. Selection and characterization of DNA aptamers against Staphylococcus aureus enterotoxin C1. Food Chemistry. 2015; 166:623-629: doi: 10.1016/j.foodchem.2014.06.039.
64. Hong KL, Battistella L, Salva AD, Williams RM, Sooter LJ. In Vitro selection of single-stranded DNA molecular recognition elements against S. Aureus alpha toxin and sensitive detection in human serum. International Journal Of Molecular Sciences. 2015; 16(2):2794-2809. DOI: 10.3390/ijms16022794.
65. Ferreira IM, de Souza Lacerda CM, de Faria LS, Correa CR, de Andrade ASR. Selection of peptidoglycan-specific aptamers for bacterial cells identification. Applied Biochemistry and Biotechnology. 2014; 174(7):2548-2556. DOI: 10.1007/s12010-014-1206-6.
66. Borsa BA, Tuna BG, Hermandez FJ, Hernandez LI, Bayramoglu G, Arica MY, et al. Staphylococcus aureus detection in blood samples by silica nanoparticles-oligonucleotides conjugates. Biosensors and Bioenergetics. 2016; 86:27-32.
67. Stoltenburg R, Schubert T, Strehlitz B. In vitro selection and interaction studies of a DNA aptamer targeting Protein A. PLoS One. 2015; 10(7):e0134403. DOI: 10.1371/journal.pone.0134403.
68. DeGrasse JA. A single-stranded DNA aptamer that selectively binds to Staphylococcus aureus enterotoxin B. PLoS One. 2012; 7(3):e33410. DOI: 10.1371/journal.pone.0033410.
69. Han SR, Lee SW. In Vitro selection of RNA aptamer specific to Salmonella Typhimurium. Journal of Microbiology and Biotechnology. 2013; 23(6):878-884. DOI: 10.4014/jmb.1212.12033
70. Moon J, Kim G, Lee S, Park S. Identification of Salmonella typhimurium-specific DNA aptamers developed using whole-cell SELEX and FACS analysis. Journal of Microbiological Methods. 2013; 95(2):162-166.
71. Lavu PSR, Mondal B, Ramlal S, Murali HS, Batra HV. Selection and characterization of aptamers using a modified whole cell bacterium SELEX for the detection of Salmonella entericaSerovar Typhimurium. ACS Combinatorial Science. 2016; 18(6):292-301. DOI: 10.1021/acscombsci.5b00123
72. Duan N, Wu S, Chen X, Huang Y, Xia Y, Ma X, et al. Selection and characterization of aptamers against Salmonella typhimurium using whole bacterium systemic evolution of ligands by exponential enrichment (SELEX). Journal of Agricultural and Food Chemistry. 2013; 61(13):3229-3234. DOI: 10.1021/jf400767d
73. Bayrac C, Eyidogan F, AvniOktem H. DNA aptamer-based colorimetric detection platform for Salmonella enteritidis. Biosensors and Bioelectronics. 2017; 98:22-28. DOI: 10.1016/j.bios.2017.06.029
74. Peng Z, Ling M, Ning Y, Deng L. Rapid fluorescent detection of Escherichia coli K88 based on DNA aptamer library as direct and specific reporter combined with immuno-magnetic sepration. Journal of Fluorescence. 2014; 24(4):1159-1168.
75. Amraee M, Oloomi M, Yavari A, Bouzari S. DNA aptamer identification and characterization for E.coli O157 detection using cell based SELEX method. Analytical Biochemistry. 2017; 536:36-44.
76. Ohk SH, Koo OK, Sen T, Yamamoto CM, Bhunia AK. Antibody-aptamer functionalized fibre-optic biosensor for specific detection of Listeria monocytogenes from food. Journal of applied Microbiology. 2010; 109(3):808-817.
77. UmamaYezdani, Mohd. Gayoor khan, NileshKushwah, Arvind Verma, Fazal Khan. Application of nanotechnology in Diagnosis and treatment of various disease and it’s future advances in medicine. World J Pharm Pharm Sci. 2018; 7(11):1611-1633.
78. UmamaYezdani, Mohd. Gayoor khan, Fazal khan, Arvind Verma, NileshKushwah, RohitVerma. The Drug Targeting in Alzheimer’s or Applications and it’s Hazards. World J Pharm Pharm Sci. 2017; 7(11):1532-1549.
79. Gayoor khan, UmamaYezdani, RohitVerma, RaqshanJabeen, Pradeep Sintha. Detection of Phlebovirus by using qualitative Real time (RT)- PCR and application of silver nanoparticles to control it. World J Pharm Pharm Sci., 2018; 7(11):936-52.
80. D.J. Stickler, J.B. King, C Winters, S.L. Morris. Blockage of urethral catheters by bacterial biofilms. Journal of Infection. 1993; 27(2):133-135.
81. Li Y, Lee HJ, Corn RM. Detection of protein biomarkers using RNA aptamer microarray and enzymatically amplified surface tension plasmon resonance imaging. Anal Chem. 2007; 79(3):1082-1088.
82. Eissa S., Zourob M. In vitro selection of DNA aptamers targeting B-lactoglobulin and their integration in graphene-based biosensor for detection of milk allergen. Biosensor. 2017; 91:169-174.
83. Weiwei Hu, Quansheng Chen, Huanhuan Li, Qin Ouyang, Jiewen Zhao. Fabricating a novel label-free aptasensons for acetamiprid by fluorescence resonance energy transfer between NH2-NaYF4:Yb, Ho@SiO2 and Au nanoparticles. Biosensors and Bioelectronics. 2016; 80:398-404.
84. Xu G, Huo D, Hou C, Zhao Y, Bao J, Yang M, Fa H. A regenerative and selective electrochemical aptasensor based on copper oxide nanoflowers-single walled carbon nanotubes nanocomposite for chorpyrifos detection. Talanta. 2018; 178:1046-1052.
85. zinha J, Reyes S.J., Gallivan J.P. Reprogramming bacteria to seek and destroy an herbicide. Nat. Chem. Biol. 2010; 6:464-470: doi: 10.1038/nchembio.369.
86. Fan L., Zhao G., Shi H., Liu M., Li Z. A highly selective electrochemical impedance spectroscopy-based aptasensor for sensitive detection of acetamiprid. Biosens. Bioelectron. 2013; 43:12-18.
87. McCauley TG, Hamaguchi N, Stanton M. Aptamer-based biosensor arrays for detection and quantification of biological macromolecules. Analytical Biochemistry. 2003; 319(2):244-250.
88. Pothoulakis G, Ceroni F, Reeve B, Ellis T. The spinach RNA Aptamer as a characterization tool for synthetic biology. ACS Synth Biol. 2014; 3(3):182-7: doi: 10.1021/sb400089c.
89. Scott D Seiwert, Theresa StinesNahreini, Stefan Aigner, Natalie G Ahn, Olke C Uhlenbeck. RNA Aptamers as pathway-specific MAP kinase inhibitors. Cell Chem Biol. 2000;7(11):833-843.
90. Paige JS, Wu KY, Jaffrey SR. RNA mimics of green fluorescent protein. Science. 2011; 333(6042):642-6. DOI: 10.1126/science.1207339.
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How to Cite
Devsing, S., Sarode, R., Khandelwal, S., & Biyani, K. (2020). Aptamer as a Targeted Drug Delivery. Asian Journal of Pharmaceutical Research and Development, 8(4), 150-159. https://doi.org/https://doi.org/10.22270/ajprd.v8i4.790