Challenges and Strategies in Prodrug Design: A Comprehensive Review Challenges and Strategies in Prodrug Design
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Abstract
The development of prodrugs represents an indispensable paradigm in contemporary pharmaceutical sciences, enabling the circumvention of intrinsic limitations associated with conventional therapeutics. By virtue of their capacity to enhance solubility, bioavailability, metabolic stability, and tissue specificity, prodrugs facilitate the optimization of pharmacokinetic and pharmacodynamics parameters, thereby augmenting therapeutic efficacy. This review meticulously delineates the fundamental principles governing prodrug design, elucidates the intrinsic challenges encountered in their development, and explores state-of-the-art strategies employed to ameliorate these limitations. A systematic evaluation of peer-reviewed literature was undertaken, encompassing authoritative sources indexed in PubMed, Scopus, and Web of Science. The selection criteria encompassed studies that expound upon chemical modification strategies, site-specific activation mechanisms, and computational methodologies for rational prodrug design. The synthesis of data was executed with rigorous scrutiny to ensure the exclusion of biases and the inclusion of seminal advancements in nanotechnology, enzyme-targeted activation, and predictive modelling. The findings underscore the pivotal role of linker chemistry, enzymatic selectivity, and stimuli-responsive constructs in refining prodrug efficacy. The advent of artificial intelligence-driven predictive models and precision medicine approaches has further revolutionized the domain, facilitating the bespoke tailoring of prodrug candidates to individual patient profiles. Despite these advancements, formidable challenges persist, particularly in ensuring precise activation kinetics, circumventing regulatory constraints, and achieving scalable industrial synthesis. The future trajectory of prodrug research necessitates a confluence of interdisciplinary expertise, integrating computational modelling, advanced bioconjugation techniques, and sustainable synthetic methodologies. A concerted effort towards the refinement of assisted delivery and biomarker-guided activation will indubitably propel the next generation of prodrugs towards clinical and commercial fruition, thereby redefining the landscape of targeted therapeutic intervention.
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Dudhe, R., Dudhe, A., Wankhede, S., Badule, A., Chaure, S., Damahe, A., & Damahe, M. (2025). Challenges and Strategies in Prodrug Design: A Comprehensive Review. Journal of Advanced Scientific Research, 16(06), 1-20. https://doi.org/10.55218/JASR.2025160601
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Review Articles
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References
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8. Daugherty, K. K., & Hume, A. L. (1997). Enalapril: An angiotensin-converting enzyme inhibitor for treatment of heart failure. Annals of Pharmacotherapy, 31(3), 365–374.
9. Sheldon, R. A. (2017). The E factor: Fifteen years on. Green Chemistry, 9(12), 1273–1283.
10. Seoane-Viaño, I., Trenfield, S. J., Basit, A. W., & Goyanes, A. (2021). Engineering complex oral formulations: 3D printing of personalized pharmaceutical dosage forms. Advanced Drug Delivery Reviews, 174, 553–582.
11. Lee, J. Y., Tan, W. S., & Ng, S. K. (2017). 3D bioprinting of human tissues: Challenges and future directions. Trends in Biotechnology, 35(8), 777–788.
12. Stella, V. J., Charman, W. N., & Naringrekar, V. H. (1985). Prodrugs: Do they have advantages in clinical practice? Drugs, 29(5), 455–473.
13. Rautio, J., Kumpulainen, H., Heimbach, T., Oliyai, R., Oh, D., Järvinen, T., & Savolainen, J. (2008). Prodrugs: Design and clinical applications. Nature Reviews Drug Discovery, 7(3), 255–270.
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18. Roche, E. B. (1987). Design of Biopharmaceutical Properties through Prodrugs and Analogs. American Pharmaceutical Association.
19. Kwon, I. K., Lee, S. C., Han, B., & Park, K. (2012). Analysis on the current status of targeted drug delivery using nanomaterials. Journal of Controlled Release, 164(2), 108–114.
20. Torchilin, V. P. (2014). Smart stimuli-responsive pharmaceutical nanocarriers. Nanomedicine, 9(2), 245–257.
21. Krall, N., Pretto, F., Decurtins, W., Bernardes, G. J., Supuran, C. T., & Neri, D. (2014). A small-molecule drug conjugate for the treatment of carbonic anhydrase IX expressing tumors. Angewandte Chemie International Edition, 53(16), 4231-4235.
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26. Cleland, J. G., McGowan, J., Clark, A. L., & Dargie, H. J. (1991). ACE inhibitors and prodrugs: Differences and consequences. European Heart Journal, 12(1), 2–9.
27. Wiviott, S. D., Braunwald, E., McCabe, C. H., et al. (2007). Prasugrel versus clopidogrel in patients with acute coronary syndromes. New England Journal of Medicine, 357(20), 2001–2015.
28. Payne, C. D., Li, Y. G., Small, D. S., et al. (2008). Inhibition of ADP-induced platelet aggregation by prasugrel compared with clopidogrel and ticlopidine in healthy subjects American Journal of Cardiology, 101(4), 616–621
29. Miwa, M., Ura, M., Nishida, M., Sawada, N., Ishikawa, T., Mori, K., & Hattori, N. (1998). Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumors. European Journal of Cancer, 34(8), 1274–1281.
30. Twelves, C., Glynne-Jones, R., Cassidy, J., et al. (2002). Capecitabine as first-line treatment in colorectal cancer: A phase III study comparing capecitabine with 5-fluorouracil/folinic acid. Journal of Clinical Oncology, 20(1), 1519–1526.
31. Mathijssen, R. H., van Alphen, R. J., Verweij, J., et al. (2001). Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clinical Cancer Research, 7(8), 2182–2194.
32. Slatter, J. G., Su, P., Sams, J. P., Schaaf, L. J., & Wienkers, L. C. (2000). Bioactivation of irinotecan to SN-38 by human hepatic microsomes: Role of carboxylesterases and UDP-glucuronosyltransferase 1A1. Cancer Research, 60(5), 1471–1477.
33. Fahn, S. (1999). The history of levodopa as it relates to Parkinson’s disease. Neurology, 50(6), S2–S10.
34. Olanow, C. W., Koller, W. C. (1998). An algorithm for the management of Parkinson’s disease: Treatment guidelines. Neurology, 50(5), S1–S57.
35. EMA (2020). Guideline on the clinical development of fixed-dose combination medicinal products. European Medicines Agency Publications.
36. FDA (2018). Assessing the effects of food on drugs in INDs and NDAs – Clinical pharmacology considerations. U.S. Food and Drug Administration.
37. Vig, B.S., Huttunen, K.M., Laine, K. and Rautio, J., 2013. Amino acids as promoieties in prodrug design and development. Advanced Drug Delivery Reviews, 65(10), pp.1370-1385.
38. Jana, S., Mandlekar, S. and Marathe, P., 2010. Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists. Current medicinal chemistry, 17(32), pp.3874-3908.
39. Supuran, C. T. (2018). Peptide prodrugs and their applications in targeted therapies. Molecules, 23(8), 1927.
40. Kumar, R., Shin, W. S., Sunwoo, K., et al. (2019). Smart cancer therapy based on pH-responsive prodrugs and nanomedicine. Biomaterials, 226, 119545.
41. Hessler, G., & Baringhaus, K.H. (2018). Artificial intelligence in drug design. Molecular Informatics, 37(12), 170011
42. Abet, V., Filace, F., Recio, J., Alvarez-Builla, J., & Burgos, C. (2017). Prodrug approach: An overview of recent cases. European journal of medicinal chemistry, 127, 810–827.
43. Gudin, J. A., & Nalamachu, S. R. (2016). An overview of prodrug technology and its application for developing abuse-deterrent opioids. Postgraduate medicine, 128(1), 97–105.
44. Prakash, C., Shaffer, C. L., & Nedderman, A. (2008). Role of biotransformation studies in reducing attrition and improving drug safety. Chemical Research in Toxicology, 21(1), 172–191.
45. Meyer, J. H., & Sluggett, G. W. (2004). Resurrecting failed drugs: The role of prodrug design. Journal of Pharmaceutical Sciences, 93(5), 1255–1271.
46. Illum, L. (2000) 'Transport of drugs from the nasal cavity to the central nervous system', European Journal of Pharmaceutical Sciences, 11(1), pp. 1–18.
47. Shojaei, A. H. (1998) 'Buccal mucosa as a route for systemic drug delivery: A review', Journal of Pharmacy & Pharmaceutical Sciences, 1(1), pp. 15–30.
48. Rao, V. M., Mandal, T. K., & Palem, C. R. (2013) 'Transdermal prodrug delivery strategies: Recent advances and future perspectives', Journal of Controlled Release, 172(3), pp. 849–865.
49. Lee, S. L., O’Connor, T. F., Yang, X., et al. (2015) 'Modernizing pharmaceutical manufacturing: From batch to continuous production', Journal of Pharmaceutical Innovation, 10(3), pp. 191–199
50. Reimer, D., & Bode, H. B. (2014). A natural prodrug activation mechanism in the biosynthesis of nonribosomal peptides. Natural product reports, 31(2), 154–159.
51. Yao, Q., Lin, F., Lu, C., Zhang, R., Xu, H., Hu, X., Wu, Z., Gao, Y., & Chen, P. R. (2023). A Dual-Mechanism Targeted Bioorthogonal Prodrug Therapy. Bioconjugate chemistry, 34(12), 2255–2262.
52. Struwe, M. A., Scheidig, A. J., & Clement, B. (2023). The mitochondrial amidoxime reducing component-from prodrug-activation mechanism to drug-metabolizing enzyme and onward to drug target. The Journal of biological chemistry, 299(11), 105306.
53. Markovic, M., Ben-Shabat, S., & Dahan, A. (2020). Computational Simulations to Guide Enzyme-Mediated Prodrug Activation. International journal of molecular sciences, 21(10), 3621.
54. Sotriffer, C. A. (2006) 'Molecular Dynamics Simulations in Drug Design', Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine, Springer, Berlin, Heidelberg. doi: 10.1007/3-540-29623-9_0820【207】.
55. Reddy, M. R., Erion, M. D. & Agarwal, A. (2000) 'Free energy calculations: use and limitations in predicting ligand binding affinities', Reviews in Computational Chemistry, 16, pp. 217–304.
56. Kiso, Y., & Nagai, U. (1993). Protecting groups in peptide synthesis. Chemical Reviews, 93(7), 2567–2581.
57. Lakka, N. S., & Naik, H. (2021). Analytical techniques for impurity profiling in pharmaceuticals. Critical Reviews in Analytical Chemistry, 51(2), 175–191.
58. Alsante, K. M., Ando, A., Brown, R., et al. (2007). The role of degradant profiling in active pharmaceutical ingredients and drug products. Advanced Drug Delivery Reviews, 59(1), 29–37
59. Hamman, J. H., Steenekamp, J. H., & Kotzé, A. F. (2015). Absorption mechanisms of peptide and protein drugs and strategies to improve absorption. Scientific World Journal, 2015, 1–14.
60. Sharpless, K. B., Kolb, H. C., & Finn, M. G. (2001). Click chemistry: A concept for functional group transformations. Angewandte Chemie International Edition, 40(11), 2004–2021.
61. Bochet, C. G. (2002). Photolabile protecting groups and linkers. Journal of the Chemical Society, Perkin Transactions 1, 125–142.
62. Rizvi, I., Anbil, S., Alagic, N., et al. (2018). Photochemical internalization-based enhancement of chemotherapeutic drug efficacy. Frontiers in Pharmacology, 9, 587.
63. Thomas, A., Teicher, B. A., & Hassan, R. (2016). Antibody–drug conjugates for cancer therapy. The Lancet Oncology, 17(6), e254–e262.
64. Pola, R., & Dwek, M. V. (2020). Bioconjugation strategies for therapeutic delivery. Bioconjugate Chemistry, 31(2), 487–509.
65. Bajorath, J. (2013). Computational approaches in medicinal chemistry: Current and future perspectives. Molecules, 18(12), 13604–13621.
66. Ferreira, M. M. C., & Cramer, S. M. (2004). QSAR modeling of drug solubility and permeability. Journal of Pharmaceutical Sciences, 93(2), 297–310.
67. Mirnezami, R., Nicholson, J., & Darzi, A. (2012). Preparing for precision medicine. New England Journal of Medicine, 366(6), 489–491.
68. Chuang, J. C., & Levine, A. D. (2013). Genomics and personalized medicine: Future directions. Current Opinion in Biotechnology, 24(4), 643–648.
69. Prasad, L. K., Smyth, H. (2016). 3D printing technologies for drug delivery: A review. Drug Development and Industrial Pharmacy, 42(7), 1019–1031.
2. Stella, V. J., & Nti-Addae, K. W. (2007). Prodrug strategies to overcome poor water solubility. Advanced Drug Delivery Reviews, 59(7), 677–694.
3. Huttunen, K. M., Raunio, H., & Rautio, J. (2011). Prodrugs—from serendipity to rational design. Pharmacological Reviews, 63(3), 750–771.
4. Kratz, F., Müller, I. A., Ryppa, C., & Warnecke, A. (2008). Prodrug strategies in anticancer chemotherapy. ChemMedChem, 3(1), 20–53.
5. Ahlawat, J., Henriquez, G., & Narayan, M. (2021). Enhancing the delivery of chemotherapeutics: Role of biodegradable polymeric nanoparticles. Molecules, 26(14), 3963.
6. Zhou, J., Rossi, J. (2017). Aptamers as targeted therapeutics: Current potential and challenges. Nature Reviews Drug Discovery, 16(3), 181–202.
7. Liu, C., Zhang, W., Li, Y., Chang, J., Tian, F., Zhao, F., Ma, Y., & Zhao, Y. (2021). RNA-based therapeutics for colorectal cancer: Updates and future directions. Journal of Experimental & Clinical Cancer Research, 40(1), 226.
8. Daugherty, K. K., & Hume, A. L. (1997). Enalapril: An angiotensin-converting enzyme inhibitor for treatment of heart failure. Annals of Pharmacotherapy, 31(3), 365–374.
9. Sheldon, R. A. (2017). The E factor: Fifteen years on. Green Chemistry, 9(12), 1273–1283.
10. Seoane-Viaño, I., Trenfield, S. J., Basit, A. W., & Goyanes, A. (2021). Engineering complex oral formulations: 3D printing of personalized pharmaceutical dosage forms. Advanced Drug Delivery Reviews, 174, 553–582.
11. Lee, J. Y., Tan, W. S., & Ng, S. K. (2017). 3D bioprinting of human tissues: Challenges and future directions. Trends in Biotechnology, 35(8), 777–788.
12. Stella, V. J., Charman, W. N., & Naringrekar, V. H. (1985). Prodrugs: Do they have advantages in clinical practice? Drugs, 29(5), 455–473.
13. Rautio, J., Kumpulainen, H., Heimbach, T., Oliyai, R., Oh, D., Järvinen, T., & Savolainen, J. (2008). Prodrugs: Design and clinical applications. Nature Reviews Drug Discovery, 7(3), 255–270.
14. Müller, C. E. (2009). Prodrug approaches for enhancing the bioavailability of drugs with low solubility. ChemMedChem, 4(3), 281–290.
15. Fleisher, D., Li, C., Zhou, Y., & Pao, L. H. (1996). Drug–enzyme interactions in prodrug therapy. Advanced Drug Delivery Reviews, 19(2), 115–130.
16. Stella, V. J., & Himmelstein, K. J. (1980). Pharmaceutical and biochemical considerations in prodrug design and evaluation. Advanced Drug Delivery Reviews, 4(1), 1–32.
17. Stella, V. J. (2004). Prodrugs as therapeutics. Expert Opinion on Therapeutic Patents, 14(3), 277–280.
18. Roche, E. B. (1987). Design of Biopharmaceutical Properties through Prodrugs and Analogs. American Pharmaceutical Association.
19. Kwon, I. K., Lee, S. C., Han, B., & Park, K. (2012). Analysis on the current status of targeted drug delivery using nanomaterials. Journal of Controlled Release, 164(2), 108–114.
20. Torchilin, V. P. (2014). Smart stimuli-responsive pharmaceutical nanocarriers. Nanomedicine, 9(2), 245–257.
21. Krall, N., Pretto, F., Decurtins, W., Bernardes, G. J., Supuran, C. T., & Neri, D. (2014). A small-molecule drug conjugate for the treatment of carbonic anhydrase IX expressing tumors. Angewandte Chemie International Edition, 53(16), 4231-4235.
22. Wagstaff, A. J., Faulds, D., & Goa, K. L. (1994). Valaciclovir: A review of its antiviral activity, pharmacokinetic properties, and therapeutic efficacy in herpesvirus infections. Drugs, 47(2), 250–279.
23. Beutner, K. R. (1995). Valacyclovir: A review of its use for the management of genital herpes. Drugs, 50(1), 7–13.
24. Sofia, M. J., Bao, D., Chang, W., et al. (2010). Discovery of a β-D-2′-deoxy-2′-α-fluoro-2′-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus. Journal of Medicinal Chemistry, 53(19), 7202–7218.
25. Kohli, A., Shaffer, A., Sherman, A., & Kottilil, S. (2014). Sofosbuvir for the treatment of hepatitis C virus infection. Clinical Infectious Diseases, 58(4), 512–521.
26. Cleland, J. G., McGowan, J., Clark, A. L., & Dargie, H. J. (1991). ACE inhibitors and prodrugs: Differences and consequences. European Heart Journal, 12(1), 2–9.
27. Wiviott, S. D., Braunwald, E., McCabe, C. H., et al. (2007). Prasugrel versus clopidogrel in patients with acute coronary syndromes. New England Journal of Medicine, 357(20), 2001–2015.
28. Payne, C. D., Li, Y. G., Small, D. S., et al. (2008). Inhibition of ADP-induced platelet aggregation by prasugrel compared with clopidogrel and ticlopidine in healthy subjects American Journal of Cardiology, 101(4), 616–621
29. Miwa, M., Ura, M., Nishida, M., Sawada, N., Ishikawa, T., Mori, K., & Hattori, N. (1998). Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumors. European Journal of Cancer, 34(8), 1274–1281.
30. Twelves, C., Glynne-Jones, R., Cassidy, J., et al. (2002). Capecitabine as first-line treatment in colorectal cancer: A phase III study comparing capecitabine with 5-fluorouracil/folinic acid. Journal of Clinical Oncology, 20(1), 1519–1526.
31. Mathijssen, R. H., van Alphen, R. J., Verweij, J., et al. (2001). Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clinical Cancer Research, 7(8), 2182–2194.
32. Slatter, J. G., Su, P., Sams, J. P., Schaaf, L. J., & Wienkers, L. C. (2000). Bioactivation of irinotecan to SN-38 by human hepatic microsomes: Role of carboxylesterases and UDP-glucuronosyltransferase 1A1. Cancer Research, 60(5), 1471–1477.
33. Fahn, S. (1999). The history of levodopa as it relates to Parkinson’s disease. Neurology, 50(6), S2–S10.
34. Olanow, C. W., Koller, W. C. (1998). An algorithm for the management of Parkinson’s disease: Treatment guidelines. Neurology, 50(5), S1–S57.
35. EMA (2020). Guideline on the clinical development of fixed-dose combination medicinal products. European Medicines Agency Publications.
36. FDA (2018). Assessing the effects of food on drugs in INDs and NDAs – Clinical pharmacology considerations. U.S. Food and Drug Administration.
37. Vig, B.S., Huttunen, K.M., Laine, K. and Rautio, J., 2013. Amino acids as promoieties in prodrug design and development. Advanced Drug Delivery Reviews, 65(10), pp.1370-1385.
38. Jana, S., Mandlekar, S. and Marathe, P., 2010. Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists. Current medicinal chemistry, 17(32), pp.3874-3908.
39. Supuran, C. T. (2018). Peptide prodrugs and their applications in targeted therapies. Molecules, 23(8), 1927.
40. Kumar, R., Shin, W. S., Sunwoo, K., et al. (2019). Smart cancer therapy based on pH-responsive prodrugs and nanomedicine. Biomaterials, 226, 119545.
41. Hessler, G., & Baringhaus, K.H. (2018). Artificial intelligence in drug design. Molecular Informatics, 37(12), 170011
42. Abet, V., Filace, F., Recio, J., Alvarez-Builla, J., & Burgos, C. (2017). Prodrug approach: An overview of recent cases. European journal of medicinal chemistry, 127, 810–827.
43. Gudin, J. A., & Nalamachu, S. R. (2016). An overview of prodrug technology and its application for developing abuse-deterrent opioids. Postgraduate medicine, 128(1), 97–105.
44. Prakash, C., Shaffer, C. L., & Nedderman, A. (2008). Role of biotransformation studies in reducing attrition and improving drug safety. Chemical Research in Toxicology, 21(1), 172–191.
45. Meyer, J. H., & Sluggett, G. W. (2004). Resurrecting failed drugs: The role of prodrug design. Journal of Pharmaceutical Sciences, 93(5), 1255–1271.
46. Illum, L. (2000) 'Transport of drugs from the nasal cavity to the central nervous system', European Journal of Pharmaceutical Sciences, 11(1), pp. 1–18.
47. Shojaei, A. H. (1998) 'Buccal mucosa as a route for systemic drug delivery: A review', Journal of Pharmacy & Pharmaceutical Sciences, 1(1), pp. 15–30.
48. Rao, V. M., Mandal, T. K., & Palem, C. R. (2013) 'Transdermal prodrug delivery strategies: Recent advances and future perspectives', Journal of Controlled Release, 172(3), pp. 849–865.
49. Lee, S. L., O’Connor, T. F., Yang, X., et al. (2015) 'Modernizing pharmaceutical manufacturing: From batch to continuous production', Journal of Pharmaceutical Innovation, 10(3), pp. 191–199
50. Reimer, D., & Bode, H. B. (2014). A natural prodrug activation mechanism in the biosynthesis of nonribosomal peptides. Natural product reports, 31(2), 154–159.
51. Yao, Q., Lin, F., Lu, C., Zhang, R., Xu, H., Hu, X., Wu, Z., Gao, Y., & Chen, P. R. (2023). A Dual-Mechanism Targeted Bioorthogonal Prodrug Therapy. Bioconjugate chemistry, 34(12), 2255–2262.
52. Struwe, M. A., Scheidig, A. J., & Clement, B. (2023). The mitochondrial amidoxime reducing component-from prodrug-activation mechanism to drug-metabolizing enzyme and onward to drug target. The Journal of biological chemistry, 299(11), 105306.
53. Markovic, M., Ben-Shabat, S., & Dahan, A. (2020). Computational Simulations to Guide Enzyme-Mediated Prodrug Activation. International journal of molecular sciences, 21(10), 3621.
54. Sotriffer, C. A. (2006) 'Molecular Dynamics Simulations in Drug Design', Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine, Springer, Berlin, Heidelberg. doi: 10.1007/3-540-29623-9_0820【207】.
55. Reddy, M. R., Erion, M. D. & Agarwal, A. (2000) 'Free energy calculations: use and limitations in predicting ligand binding affinities', Reviews in Computational Chemistry, 16, pp. 217–304.
56. Kiso, Y., & Nagai, U. (1993). Protecting groups in peptide synthesis. Chemical Reviews, 93(7), 2567–2581.
57. Lakka, N. S., & Naik, H. (2021). Analytical techniques for impurity profiling in pharmaceuticals. Critical Reviews in Analytical Chemistry, 51(2), 175–191.
58. Alsante, K. M., Ando, A., Brown, R., et al. (2007). The role of degradant profiling in active pharmaceutical ingredients and drug products. Advanced Drug Delivery Reviews, 59(1), 29–37
59. Hamman, J. H., Steenekamp, J. H., & Kotzé, A. F. (2015). Absorption mechanisms of peptide and protein drugs and strategies to improve absorption. Scientific World Journal, 2015, 1–14.
60. Sharpless, K. B., Kolb, H. C., & Finn, M. G. (2001). Click chemistry: A concept for functional group transformations. Angewandte Chemie International Edition, 40(11), 2004–2021.
61. Bochet, C. G. (2002). Photolabile protecting groups and linkers. Journal of the Chemical Society, Perkin Transactions 1, 125–142.
62. Rizvi, I., Anbil, S., Alagic, N., et al. (2018). Photochemical internalization-based enhancement of chemotherapeutic drug efficacy. Frontiers in Pharmacology, 9, 587.
63. Thomas, A., Teicher, B. A., & Hassan, R. (2016). Antibody–drug conjugates for cancer therapy. The Lancet Oncology, 17(6), e254–e262.
64. Pola, R., & Dwek, M. V. (2020). Bioconjugation strategies for therapeutic delivery. Bioconjugate Chemistry, 31(2), 487–509.
65. Bajorath, J. (2013). Computational approaches in medicinal chemistry: Current and future perspectives. Molecules, 18(12), 13604–13621.
66. Ferreira, M. M. C., & Cramer, S. M. (2004). QSAR modeling of drug solubility and permeability. Journal of Pharmaceutical Sciences, 93(2), 297–310.
67. Mirnezami, R., Nicholson, J., & Darzi, A. (2012). Preparing for precision medicine. New England Journal of Medicine, 366(6), 489–491.
68. Chuang, J. C., & Levine, A. D. (2013). Genomics and personalized medicine: Future directions. Current Opinion in Biotechnology, 24(4), 643–648.
69. Prasad, L. K., Smyth, H. (2016). 3D printing technologies for drug delivery: A review. Drug Development and Industrial Pharmacy, 42(7), 1019–1031.