Authors : Dr. Binny Mehta; SaadHusain Shaikh; Zaid Saiyed

Volume/Issue : Volume 11 - 2026, Issue 4 - April

Google Scholar : https://tinyurl.com/3ujynrj2

Scribd : https://tinyurl.com/ypse55fj

DOI : https://doi.org/10.38124/ijisrt/26apr1847

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Controlled drug delivery (CDD) is a specialized pharmaceutical strategy in which engineered carrier systems are employed to modulate the speed, timing, and anatomical site of drug release within the body. Conventional immediate-release formulations frequently fall short due to inadequate bioavailability, imprecise targeting, and poor patient adherence. In contrast, CDD platforms are designed to sustain drug concentrations within the therapeutic window over prolonged intervals, thereby curtailing the plasma fluctuations that otherwise precipitate either toxicity or subtherapeutic outcomes. Among their chief advantages are the reduction of dosing frequency and the promotion of patient adherence, particularly in the long-term management of chronic illnesses. This article surveys recent progress in CDD, focusing on three major technological frontiers: (i) nanotechnology-based CDD, which harnesses nanocarriers such as liposomes and polymeric nanoparticles for site-selective cancer targeting via passive and active mechanisms; (ii) stimuli-responsive drug delivery systems (SRDDS), which are engineered to release their therapeutic payload in response to biological or physicochemical cues including pH shifts, thermal gradients, and redox states; and (iii) targeted drug delivery strategies, including novel approaches that exploit the endocannabinoid system. Advanced fabrication methods such as microfluidics and electrospinning have further propelled the field by enabling more reproducible, uniform drug carriers. Notwithstanding this considerable progress, several obstacles continue to impede broader clinical adoption. These encompass navigating intrinsic biological barriers such as the blood-brain barrier and mucosal interfaces, resolving safety and toxicity concerns around biomaterial compatibility and erratic release kinetics, and closing the clinical translation gap that persists due to overly simplified preclinical models and complex scale-up requirements. Prospectively, CDD is well-positioned to underpin personalised and precision medicine, enabling treatment regimens calibrated to individual genomic profiles. The discipline will be further transformed by the incorporation of Artificial Intelligence and Machine Learning, which promise to accelerate formulation optimization and strengthen predictive modelling.

Keywords : Controlled Drug Delivery, Sustained Release, Bioavailability, Patient Compliance, Targeted Delivery, Polymers, Liposomes, Nanoparticles, Biodegradable Materials, Diffusion, Degradation, Stimuli-Responsive Systems, Nanotechnology, Microfluidics, Electrospinning, Artificial Intelligence, Machine Learning, Cancer Therapy, Personalized Medicine, Passive Targeting, Active Targeting, Biological Barriers, Blood-Brain Barrier, Toxicity, Biocompatibility, Clinical Translation, Regulatory Challenges, Smart Drug Delivery Systems.

References :

1. Siepmann J, Siepmann F. Modeling of diffusion controlled drug delivery. J Controlled Release. 2012 July 20;161(2):351–62.
2. Loke YH, Jayakrishnan A, Razif MRFM, Yee KM, Kee PE, Goh BH, et al. A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies. http://www.eurekaselect.com [Internet]. [cited 2025 Sept 1]; Available from: https://www.eurekaselect.com/article/143781
3. Virmani T, Kumar G, Sharma A, Pathak K. An overview of ocular drug delivery systems—conventional and novel drug delivery systems. In: Nanotechnology in Ophthalmology [Internet]. Elsevier; 2023 [cited 2025 Sept 1]. p. 23–48. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780443152641000075
4. Novel Drug Delivery Systems: An Important Direction for Drug Innovation Research and Development [Internet]. [cited 2025 Sept 1]. Available from: https://www.mdpi.com/1999-4923/16/5/674
5. Hamzy IA, Alqhoson AI, Aljarbou AM, Alhajri MA. An in-depth overview of controlled drug delivery systems: Present developments and prospective advancements. Int J Health Sci. 2022 Jan 15;6(S10):1755–70.
6. http://www.eurekaselect.com [Internet]. [cited 2025 Sept 1]. Controlled Drug Delivery Systems: Concepts and Rationale. Available from: http://www.eurekaselect.com/chapter/23899
7. Chaudhary NK, R. Rajbhar MrR, Dr. RashidIqbal DrR. “Controlled Drug Delivery System.” Int J Pharm Res Appl. 2025 Apr;10(4):277–88.
8. Swarnalatha KM, Iswariya VT, Akash B, Bhandari S, Shirisha R, Ramarao T. A Comprehensive Review of Controlled Drug Release Delivery Systems: Current Status and Future Directions. Int J Pharm Phytopharm Res. 2024;14(2–2024):24–30.
9. Kanaujia I. ADVANCED DRUG DELIVERY SYSTEM. In: Philip DrS, Vatsa DrE, Prajapati R, R Karthi, B GBhavani, Swain MP, et al., editors. Futuristic Trends in Pharmacy & Nursing Volume 3 Book 10 [Internet]. First. Iterative International Publisher, Selfypage Developers Pvt Ltd; 2024 [cited 2025 Oct 15]. p. 163–82. Available from: https://www.iipseries.org/viewpaper.php?pid=3056&pt=advanced-drug-delivery-system
10. Kumari S, R Rajbhar MrR. Controlled drug delivery systems. Int J Pharm Res Appl. 2025 Apr;10(4):309–16.
11. Mehrotra S, Pathak K. Chapter 1 - Controlled release drug delivery systems: principles and design. In: Nayak AK, Sen KK, editors. Novel Formulations and Future Trends [Internet]. Academic Press; 2024 [cited 2025 Oct 15]. p. 3–30. Available from: https://www.sciencedirect.com/science/article/pii/B978032391816900014X
12. Guo X, Luo Z, Cui H, Wang J, Jiang Q. A novel and reproducible release mechanism for a drug-delivery system in the gastrointestinal tract. Biomed Microdevices. 2019 Feb 27;21(1):25.
13. Sinha VR, Sharma S, Silki, Kaur M, Sarwal A. 6 - Current Polyesteric Systems for Advanced Drug Delivery. In: Holban AM, Grumezescu AM, editors. Nanoarchitectonics for Smart Delivery and Drug Targeting [Internet]. William Andrew Publishing; 2016 [cited 2025 Oct 15]. p. 143–68. Available from: https://www.sciencedirect.com/science/article/pii/B9780323473477000069
14. Saranya S, Radha KV. Review of Nanobiopolymers for Controlled Drug Delivery. Polym-Plast Technol Eng. 2014 Oct 30;53(15):1636–46.
15. Narasimhan B, Kipper MJ. SURFACE-ERODIBLE BIOMATERIALS FOR DRUG DELIVERY. In: Advances in Chemical Engineering [Internet]. Academic Press; 2004 [cited 2025 Oct 15]. p. 169–218. (Advances in Chemical Engineering: Molecular and Cellular Foundations of Biomaterials; vol. 29). Available from: https://www.sciencedirect.com/science/article/pii/S0065237703290062
16. Bao H, Wang N, Guo J, Han X. Applications of Biodegradable Polymeric Nanomaterials as Drug Delivery Systems. http://www.eurekaselect.com [Internet]. [cited 2025 Oct 15]; Available from: https://www.eurekaselect.com/article/149750
17. Faculty of Pharmacy Kampala International University Uganda, Nankya W. Nanotechnology in Cancer Treatment: Targeted Drug Delivery. Res Output J Public Health Med. 2024 Nov 23;4(2):38–42.
18. Pranita Sanjay Dudhe, Rutuja Thakare. Targeted Drug Delivery in Cancer Therapy. Int J Adv Res Sci Commun Technol. 2024 Dec 4;109–24.
19. Sengar A. The Role of Nanotechnology in Revolutionizing Cancer Treatment [Internet]. Preprints; 2025 [cited 2025 Oct 15]. Available from: https://www.preprints.org/manuscript/202503.0713/v1
20. Mittal M, Juneja S, Pandey N, Mittal R. Nanoparticle-Based Drug Delivery Systems: Current Advances and Future Directions. Curr Drug Targets. 26:1–23.
21. Nandhini Chitikela, Chaitanya B. Current Advances in Nanotechnology-Based Drug Delivery Systems: Review Article. J Pharma Insights Res. 2025 Feb 5;3(1):327–34.
22. Kallepalli B, Garg U, Jain N, Nagpal R, Malhotra S, Tiwari T, et al. Intelligent Drug Delivery: Pioneering Stimuli-Responsive Systems to Revolutionize Disease Management- An In-depth Exploration. Curr Drug Deliv. 22(2):195–214.
23. Lopes JR, Santos G, Barata P, Oliveira R, Lopes CM. Physical and Chemical Stimuli-Responsive Drug Delivery Systems: Targeted Delivery and Main Routes of Administration. http://www.eurekaselect.com [Internet]. [cited 2025 Oct 15]; Available from: https://www.eurekaselect.com/article/56368
24. Subramanian J, Padhy R, Arun J, Murthannagari VR, Gnk G. STIMULI-RESPONSIVE DRUG DELIVERY SYSTEMS: EXTENSIVE OVERVIEW. Int J Appl Pharm. 2025 Sept 7;94–106.
25. Patel K, Patel N, Gupta MA, Patel CN. An Overview on Stimuli Sensitive Drug Delivery System. Int J Innov Sci Res Technol IJISRT. 2024 Mar 13;1788–94.
26. Wang ZY, Song J, Zhang DS. Nanosized As2 O3 /Fe2 O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells. World J Gastroenterol. 2009;15(24):2995.
27. Mateen MAM, Hatwar PR, Solanki TV, Bakal RL, Karule VG, Mateen MAM, et al. Targeted drug delivery in cancer therapy: A promising approach for effective treatment. GSC Biol Pharm Sci. 2025;32(3):132–40.
28. Macadangdang RR, Agrawal R, Bhushan B, Garg A, Singh K, Kumar S, et al. Nanotechnology Integrated Innovative Drug Delivery and Therapy for Cancer. Curr Pharm Biotechnol. 26(8):1189–206.
29. Dasram MH, Walker RB, Khamanga SM. Recent Advances in Endocannabinoid System Targeting for Improved Specificity: Strategic Approaches to Targeted Drug Delivery. Int J Mol Sci. 2022 Jan;23(21):13223.
30. Yu H, Yang Z, Li F, Xu L, Sun Y. Cell-mediated targeting drugs delivery systems. Drug Deliv. 2020 Jan 1;27(1):1425–37.
31. Haq M MU. Revolutionizing Drug Delivery: Targeted Approaches and Innovations for Effective Treatment. Pharm Drug Regul Aff J. 2023 June 29;6(1):1–8.
32. Velmurugan K, Kulkarni MB, Gupta I, Das R, Goel S, Nirmal J. Role of Microfluidics in Drug Delivery. In: Mohanan PV, editor. Microfluidics and Multi Organs on Chip [Internet]. Singapore: Springer Nature; 2022 [cited 2025 Oct 15]. p. 107–33. Available from: https://doi.org/10.1007/978-981-19-1379-2_5
33. Mohammadi M, Ahmed Qadir S, Mahmood Faraj A, Hamid Shareef O, Mahmoodi H, Mahmoudi F, et al. Navigating the future: Microfluidics charting new routes in drug delivery. Int J Pharm. 2024 Apr;124142.
34. Aceves-Serrano LG, Ordaz-Martinez KA, Vazquez-Piñon M, Hwang H. Microfluidics for drug delivery systems. In: Nanoarchitectonics in Biomedicine [Internet]. Elsevier; 2019 [cited 2025 Oct 15]. p. 55–83. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780128162002000025
35. Chakraborty R, Parvez S. Microfluidics in Drug Delivery. In: Mohanan PV, editor. Microfluidics and Multi Organs on Chip [Internet]. Singapore: Springer Nature; 2022 [cited 2025 Oct 15]. p. 135–62. Available from: https://doi.org/10.1007/978-981-19-1379-2_6
36. Alkhatib H, Rahal OA, Hossain MS, Mawazi SM. Recent Advances in Electrospraying and Electrospinning Technologies. In: Electrospraying and Electrospinning in Drug Delivery. CRC Press; 2025.
37. Kaliki IS, Kabissa JP, Singh PK, Sharma S. Advances in Drug Delivery Systems: Review Article. J Pharma Insights Res. 2024 June 6;2(3):088–95.
38. Pillai A, Bhande D, Pardhi V. Controlled Drug Delivery System. In: Santra TS, Shinde AUS, editors. Advanced Drug Delivery: Methods and Applications [Internet]. Singapore: Springer Nature; 2023 [cited 2025 Oct 15]. p. 267–89. Available from: https://doi.org/10.1007/978-981-99-6564-9_11
39. Jangid A kumar, Dev R, Sharma S, Bhatnagar P. REVOLUTIONIZING THERAPEUTICS: ADVANCES, CHALLE- NGES, AND FUTURE HORIZONS IN CONTROLLED RELEASE DRUG DELIVERY SYSTEMS. Curr Res Pharm Sci. 2025 Aug 14;20–39.
40. Barzegar-fallah A, Houlton J, Barwick D, Shavandi A, Ali MA, Clarkson AN, et al. Chapter 19 - From barriers to bridges; glycans in nonparenteral nanomedicines. In: Kesharwani P, Taurin S, Greish K, editors. Theory and Applications of Nonparenteral Nanomedicines [Internet]. Academic Press; 2021 [cited 2025 Oct 16]. p. 467–87. Available from: https://www.sciencedirect.com/science/article/pii/B9780128204665000193
41. Vanshita, Garg A, Dewangan HK. Recent Advances in Drug Design and Delivery Across Biological Barriers Using Computational Models. http://www.eurekaselect.com [Internet]. [cited 2025 Oct 16]; Available from: https://www.eurekaselect.com/article/120675
42. Narayanaswamy R, Attia SA, Torchilin VP. Parameters and Strategies to Overcome Barriers to Systemic Delivery. In: Lai WF, editor. Systemic Delivery Technologies in Anti-Aging Medicine: Methods and Applications [Internet]. Cham: Springer International Publishing; 2020 [cited 2025 Oct 16]. p. 447–75. Available from: https://doi.org/10.1007/978-3-030-54490-4_19
43. Rubinstein A, Robinson JR. Controlled Drug Delivery. In: Debus E, Grossmann CJ, Hubbuch AP, Lanners HN, Linke R, Perkins ME, et al., editors. Control of Immune Response by Endocrine Factors Malaria Vaccine Controlled Drug Delivery Enzyme-Immunoassay. Berlin, Heidelberg: Springer; 1987. p. 71–107.
44. Voronin DV, Abalymov AA, Svenskaya YI, Lomova MV. Key Points in Remote-Controlled Drug Delivery: From the Carrier Design to Clinical Trials. Int J Mol Sci. 2021 Jan;22(17):9149.
45. Adepu S, Ramakrishna S. Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules. 2021 Jan;26(19):5905.
46. Gunisetty H, Balagani PK. Transdermal Drug Delivery System: An Update of Upcoming Evolution. J Compr Pharm. 2016;03(01):23–33.
47. Shukla SS, Pandey RK, Kalyani G, Shukla SS, Pandey RK, Kalyani G. https://services.igi-global.com/resolvedoi/resolve.aspx?doi=10.4018/978-1-7998-8908-3.ch008. IGI Global Scientific Publishing; 1 AD [cited 2025 Oct 16]. Controlled Drug Delivery Systems: Contemporary Significance and Advances – Overview and Advances for Controlled Drug Delivery Systems. Available from: https://www.igi-global.com/gateway/chapter/www.igi-global.com/gateway/chapter/300406
48. Nayak R, Meerovich I, Dash AK. Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems for Cancer Treatment. AAPS PharmSciTech. 2019 Apr 9;20(4):160.
49. Pircalabioru GG, Chifiriuc MC. Nanoparticulate Drug-Delivery Systems for Fighting Microbial Biofilms: From Bench to Bedside. Future Microbiol. 2020 May;15(8):679–98.
50. Steeves JD. Chapter 11 - Bench to bedside: challenges of clinical translation. In: Dancause N, Nadeau S, Rossignol S, editors. Progress in Brain Research [Internet]. Elsevier; 2015 [cited 2025 Oct 16]. p. 227–39. (Sensorimotor Rehabilitation; vol. 218). Available from: https://www.sciencedirect.com/science/article/pii/S0079612314000417
51. Ronaldson PT, Williams EI, Betterton RD, Stanton JA, Nilles KL, Davis TP. CNS Drug Delivery in Stroke: Improving Therapeutic Translation From the Bench to the Bedside. Stroke. 2024 Jan;55(1):190–202.
52. Hua S, de Matos MBC, Metselaar JM, Storm G. Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization. Front Pharmacol [Internet]. 2018 July 17 [cited 2025 Oct 16];9. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00790/full
53. Thore PP, Bhatjire GS, Shirsath VV, Jadhav AG. Innovations in pharmaceutical formulation and delivery system [Internet]. Deep Science Publishing; 2025 [cited 2025 Oct 16]. Available from: https://www.deepscienceresearch.com/dsr/catalog/book/209/chapter/835
54. Shaikh S, Satpute, R, Satpute A, Omkar S, Pawar MrV. “A Perceptive Review on Advancement in Drug Delivery System”. Int J Pharm Res Appl. 2024 May;09(05):495–504.
55. Vora LK, Gholap AD, Jetha K, Thakur RRS, Solanki HK, Chavda VP. Artificial Intelligence in Pharmaceutical Technology and Drug Delivery Design. Pharmaceutics. 2023 July;15(7):1916.
56. Wang Y, Shao W, Lin J, Zheng S. Intelligent Drug Delivery Systems: A Machine Learning Approach to Personalized Medicine [Internet]. Engineering; 2025 [cited 2025 Oct 16]. Available from: https://www.preprints.org/manuscript/202504.2570/v1
57. Oladosu MA, Abah MA, Agbo LI, Akinwande PS, Babalola MT, Imitini IOE Delta State, Nigeria, et al. Role of Artificial Intelligence in Oral Drug Delivery Optimization: A Systematic Review of Current Applications and Future Perspectives (Preprint) [Internet]. JMIR AI; 2025 [cited 2025 Oct 16]. Available from: http://preprints.jmir.org/preprint/79287
58. Ravindran R, Muthusamy S, Mohan AA. Machine Learning in Formulation Development and Optimization of Controlled Drug Delivery Systems. In: Vijaykumar H, Urbana Ivy BP, Kumar RR, G N, editors. Multidisciplinary Engineering Applications of Artificial Intelligence in Design Control and Infrastructure Systems [Internet]. 2025th ed. RADemics Research Institute; 2025 [cited 2025 Oct 16]. p. 339–62. Available from: https://www.rademics.com/chapter.php? id=67&cid=12
59. Prajapati VD, Shrivastav P, Suthar K. Controlled Drug Delivery Systems: Concepts and Rationale. In: Mundada AS, Chaudhari A, editors. Novel Drug Delivery Systems (Part 1) [Internet]. BENTHAM SCIENCE PUBLISHERS; 2024 [cited 2025 Oct 16]. p. 1–38. Available from: https://www.eurekaselect.com/node/236753
60. Sapsford KE, Lauritsen K, Tyner KM. Current Perspectives on the US FDA Regulatory Framework for Intelligent drug-delivery Systems. Ther Deliv. 2012 Dec 1;3(12):1383–94