Engineering Advances in Modern Drug Delivery Devices: Current Technologies, Challenges, and Future Directions
DOI:
https://doi.org/10.64229/4jcqvb12Keywords:
Prefilled syringes, Autoinjectors, Microneedle patches, Nanoparticle delivery systems, Bioprinting, BiosimilarsAbstract
Background: The expansion of biologics, Gene therapies and personalized medicine has been significant ever since it was initiated in the late 20th century which created an immediate need for advanced drug delivery platforms that could enhance therapeutic output, improve patient compliance and precision-in-treatment. So far, traditional routes of oral and parenteral administration are commonly hampered by limited bioavailability, systemic adverse effects, and poor patient compliance; thus, driving next-generation delivery technologies. Key Technologies Reviewed: The aim of this review is to critically evaluate state-of-the-art developments in drug delivery devices and systems-including prefilled syringes (PFSs) and autoinjectors; inhalation-based delivery platforms; microneedle (MN) patches; nanoparticle-enabled delivery systems; tissue-engineered scaffolds; and advanced transdermal technologies. These platforms are engineered to address biological limitations, improve site-specific drug targeting, and facilitate minimally invasive or self-administered therapies. Engineering and Clinical Aspects: Great strides have been made with respect to advances in device engineering, biomaterials, particle design, microfabrication and digital health integration. However, autoinjectors and very recently prefilled syringes have emerged as the devices of choice for improving dosing accuracy and patient convenience; inhalation systems and MN technologies have offered new options for non-invasive delivery. Nanoparticle-based platforms have shown improved targeting and controllable delivery of therapeutics, especially for complex therapies. The drug delivery device market worldwide is anticipated to exceed due USD 450 billion by the year 2030, a reflection of how clinically relevant these technologies have become. Future Outlook: Among current innovations, the most transformative advances in minimally invasive delivery uses MN systems and nanoparticle-enabled precision delivery to overcome significant barriers of bioavailability, therapeutic targeting and patient acceptability. Nonetheless, large-scale manufacturing, long-term safety assessment, regulatory harmonization and cost-effective commercialization still represent some of the main hurdles towards broader clinical translation. Future technologies will be dependent on the incorporation of artificial intelligence, smart sensors and customized manufacturing strategies to progress towards precision medicine and patient-centered health care.
References
[1]Guo J, Sun YM, Zhang DD, Yan J, Ji SY, Chen W, et al. FDA approved PFS-based autoinjectors: Evolution, market trends, and development challenges. Expert Opinion on Drug Delivery, 2026, 23(3), 481-494. DOI: 10.1080/17425247.2025.2585166
[2]Alkeefo R, Hotz C, Kolacyak D. Impact of dimensional variability of primary packaging materials on the break-loose and gliding forces of prefilled syringes. PDA Journal of Pharmaceutical Science and Technology, 2024, 78(5), 572-585. DOI: 10.5731/pdajpst.2023.012916
[3]Phillips JT, Fox E, Grainger W, Tuccillo D, Liu, S, Deykin A. An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects. BMC Neurology, 2011, 11, 126. DOI: 10.1186/1471-2377-11-126
[4]Tang H, Civoli F, Tatarewicz S, Vandenkoornhuyse N, Finck B. Pharmacokinetic and pharmacodynamic bioequivalence of pegfilgrastim-cbqv delivered via a prefilled autoinjector and prefilled syringe in healthy male participants. Advances in Therapy, 2023, 4889-4906. DOI: 10.1007/s12325-023-02636-5
[5]Tang H, Civoli F, Tatarewicz S, Vandenkoornhuyse N, Finck B. A randomized, open-label study conducted to evaluate the bioequivalence of pegfilgrastim-cbqv on-body injector versus prefilled syringe in healthy male participants. Advances in Therapy, 2024, 991-1009. DOI: 10.1007/s12325-023-02735-3
[6]Roszkiewicz J, Swacha Z, Smolewska E. Prefilled pen versus prefilled syringe: A pilot study evaluating two different methods of methotrexate subcutaneous injection in patients with JIA. Pediatric Rheumatology, 2020, 18, 64. DOI: 10.1186/s12969-020-00455-4
[7]Hill RL, Wilmot JG, Belluscio BA, Cleary K, Lindisch D, Tucker R, et al. Comparison of drug delivery with autoinjector versus manual prefilled syringe and between three different autoinjector devices administered in pig thigh. Medical Devices Evidence and Research, 2016, 9, 257-266. DOI: 10.2147/mder.s83406
[8]Mochizuki M, Maeda H. Trends in the market for drug delivery devices categorized as combination drugs and medical devices and regulatory challenges for autoinjectors in Japan. Frontiers in Medical Technology, 2024, 6, 1461460. DOI: 10.3389/fmedt.2024.1461460
[9]Ibrahim M, Verma R, Garcia-Contreras L. Inhalation drug delivery devices: Technology update. Medical Devices, 2015, 8, 131-139. DOI: 10.2147/mder.s48888
[10]Dongare SL, Narkhede MR. An overview of recently published patents on pulmonary drug deliverydevices. Recent Advances in Drug Delivery and Formulation, 2023. DOI: 10.2174/2667387817666230426150804
[11]Azimi S, Arzanpour S. Enhancing inhalation drug delivery: A comparative study and design optimization of a novel valved holding chamber. Journal of Biomechanical Engineering, 2024, 146(4), 041002. DOI: 10.1115/1.4064436
[12]Xiroudaki S, Schoubben A, Giovagnoli S, Rekkas DM. Dry powder inhalers in the digitalization era: Current status and future perspectives. Pharmaceutics, 2021, 1455. DOI: 10.3390/pharmaceutics13091455
[13]Acosta MF, Muralidharan P, Grijalva CL, Abrahamson MD, Hayes D, Fineman JR, et al. Advanced therapeutic inhalation aerosols of a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor for targeted pulmonary drug delivery in pulmonary hypertension: design, characterization, aerosolization, in vitro 2D/3D human lung cell cultures, and in vivo efficacy. Therapeutic Advances in Respiratory Disease, 2021, 15, 1753466621998245. DOI: 10.1177/1753466621998245
[14]Woodward IR, Fromen CA. Recent developments in aerosol pulmonary drug delivery: New technologies, new cargos, and new targets. PubMed Central, 2024, 26(1), 307-330. DOI: 10.1146/annurev-bioeng-110122-010848
[15]Cazzola M, Cavalli F, Usmani OS, Rogliani P. Advances in pulmonary drug delivery devices for the treatment of chronic obstructive pulmonary disease. Expert Opinion on Drug Delivery, 2020, 17(5), 635-646. DOI: 10.1080/17425247.2020.1739021
[16]Wang C, Gaurkhede SG, Liu MJ, Zhou YG. Electrosprayed micro-to-nanoscale particles with tunable morphologies and compositions for pulmonary drug delivery applications and inhalation therapies: A review. ACS Biomaterials Science & Engineering, 2025, 5237-5263. DOI: 10.1021/acsbiomaterials.5c00986
[17]Liu JZ, Wu ZH, Liu YD, Zhan Z, Yang LP, Wang C, et al. ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling. Journal of Nanobiotechnology, 2022, 20(1), 213. DOI: 10.1186/s12951-022-01435-4
[18]Khan A, Mishra P, Gupta D, Kumari P. Advances in transdermal drug delivery systems: From patches to microneedles. Journal of Drug Discovery and Health Sciences, 2024, 1(2), 105-112. DOI: 10.21590/jddhs.01.02.06
[19]Li Y, Chen K, Pang Y, Zhang J, Wu M, Xu Y, et al. Multifunctional microneedle patches via direct ink drawing of nanocomposite lnks for personalized transdermal drug delivery. ACS Nano, 2023, 17(20), 19925-19937. DOI: 10.1021/acsnano.3c04758
[20]Zhang LQ, Zhu CX, Shi JK, Zhou ZR, Ge DH. Design of three-section microneedle towards low insertion force and high drug delivery amount using the finite element method. Computer Methods in Biomechanics & Biomedical Engineering, 2024, 27(2), 156-166. DOI: 10.1080/10255842.2023.2174019
[21]Miura S, Aoyagi K, Nakazawa Y, Endo S, Kuroda T, Kawai T, et al. Fabrication and evaluation of dissolving hyaluronic acid microneedle patches for minimally invasive transdermal drug delivery by nanoimprinting. PubMed Central, 2025, 11(2), 89. DOI: 10.3390/gels11020089
[22]Colombo S, Beck-Broichsitter M, Bøtker JP, Malmsten M, Rantanen J, Bohr A. Transforming nanomedicine manufacturing toward Quality by Design and microfluidics. Advanced Drug Delivery Reviews, 2018, 128, 115-131. DOI: 10.1016/j.addr.2018.04.004
[23]Shukla S, Huston RH, Cox BD, Satoskar AR, Narayan RJ. Transdermal delivery via medical device technologies. Expert Opinion on Drug Delivery, 2022, 19(11), 1505-1519. DOI: 10.1080/17425247.2022.2135503
[24]Han N, Li FJ, Zhu HQ, Li T, Wang XT, Li T, et al. Comprehensive analysis of WOX transcription factors provide insight into genes related to the regulation of unisexual flowers development in Akebia trifoliata. International Journal of Biological Macromolecules, 2024, 260, 129486. DOI: 10.1016/j.ijbiomac.2024.129486
[25]Wang YP, Wang HZ, Zhu XX, Guan Y, Zhang YJ. Smart microneedle patches for rapid, and painless transdermal insulin delivery. Journal of Materials Chemistry. B, 2020, 8(40), 9335-9342. DOI: 10.1039/d0tb01822h
[26]Dafe VN, Hatwar PR, Bakal RL, Kubde JA, Jumde KS. Transdermal insulin delivery via microneedle technology, patches, and pumps offers a promising alternative to traditional subcutaneous injections for diabetes management. GSC Biological and Pharmaceutical Sciences, 2024, 29(1), 233-242. DOI: 10.30574/gscbps.2024.29.1.0372
[27]Yang J, Chen Z, Ye R, Li J, Lin Y, Gao J, et al. Touch-actuated microneedle array patch for closed-loop transdermal drug delivery. Drug Delivery, 2018, 25(1), 1728-1739. DOI: 10.1080/10717544.2018.1507060
[28]Peláez MJ, Ruiz-Ramírez J, Shen Y, Birur RM, Schiavone C, Cristini V, et al. Mechanistic modeling for optimal design of dissolvable microneedle-based patches for transdermal drug delivery. Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2023, 1-4. DOI: 10.1109/embc40787.2023.10341093
[29]Parrilla M, Detamornrat U, Domínguez‐Robles J, Tunca S, Donnelly RF, Wael KD. Wearable microneedle-based array patches for continuous electrochemical monitoring and drug delivery: Toward a closed-loop system for methotrexate treatment. ACS Sensors, 2023, 8(11), 4161-4170. DOI: 10.1021/acssensors.3c01381
[30]McGuckin MB, Moffett NM, Donnelly RF, McCrudden CM. Transdermal delivery of pramipexole using microneedle technology for the potential treatment of parkinson’s disease. Molecular Pharmaceutics, 2024, 21(5), 2512-2533. DOI: 10.1021/acs.molpharmaceut.4c00065
[31]Bahnick AJ, Sato K, Slezak DM, Kim J, Keller KM, Li Y, et al. Controlled transdermal delivery of dexamethasone for pain management via photochemically 3D‐printed bioresorbable microneedle arrays. Advanced Healthcare Materials, 2024, 13(31), e2402113. DOI: 10.1002/adhm.202402113
[32]Chen Q, Cheng YY, Huang ZH, Du S, Lyu QQ, Chen SB, et al. All-drug glassy microneedle patches for instant transdermal delivery. Advanced Materials, 2026, 38(2), e12849. DOI: 10.1002/adma.202512849
[33]Maurya A, Tyagi S. Recent advances in nanoparticle-based drug delivery systems. Journal of Drug Discovery and Health Sciences, 2024, 1(4), 201-211. DOI: 10.21590/jddhs.01.04.03
[34]Ahmad A, Youssef O, Tareq KA. Advancing precision medicine through nanotechnology-enabled drug delivery systems. Fusion of Multidisciplinary Research An International Journal, 2025, 6(2), 829-846. DOI: 10.63995/iice3293
[35]Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery, 2021, 20, 101-124. DOI: 10.1038/s41573-020-0090-8
[36]Chen KF, Yang HF, Cai R. Microfluidics for nanomedicine delivery. ACS Biomaterials Science & Engineering, 2025, 11(2), 774-783. DOI: 10.1021/acsbiomaterials.4c02052
[37]Kapoor DU, Sharma JB, Gandhi SM, Prajapati BG. AI-driven design and optimization of nanoparticle-based drug delivery systems. Scientific and Engineering Health Systems, 2024, 24010003. DOI: 10.69598/sehs.18.24010003
[38]Cheng RY, Wang SQ. Cell-mediated nanoparticle delivery systems: Towards precision nanomedicine. Drug Delivery and Translational Research, 2024, 14, 3032-3054. DOI: 10.1007/s13346-024-01591-0
[39]Chaudhari KS, Patil AR, Sonawane OS, Suryawanshi M. Advancements and challenges in targeted drug delivery systems: A path toward precision medicine. International Journal for Research in Applied Science and Engineering Technology, 2025, 161-165. DOI: 10.22214/ijraset.2025.68180
[40]Gupta PK, “Nanoparticle-based drug delivery systems for targeting tumor microenvironment,” International Journal of Scientific Research in Engineering and Management, 2023. DOI: 10.55041/ijsrem25179
[41]de Jong B, Barros ER, Hoenderop JGJ, Rigalli JP. Recent advances in extracellular vesicles as drug delivery systems and their potential in precision medicine. Pharmaceutics, 2020, 12(11), 1006. DOI: 10.3390/pharmaceutics12111006
[42]Nguyen PHD, Jayasinghe MK, Le AH, Peng B, Le MTN. Advances in drug delivery systems based on red blood cells and their membrane-derived nanoparticles. ACS Nano, 2023, 17(6), 5187-5210. DOI: 10.1021/acsnano.2c11965
[43]Bagga H, Aliunui A, Chaudhari G, Vyas U. Innovating pharmaceuticals: The rise of 3D printing in drug delivery. International Journal of Drug Delivery Technology, 2024, 14(3), 1791-1800. DOI: 10.25258/ijddt.14.3.76
[44]Singhvi G, Patil S, Girdhar V, Chellappan DK, Gupta G, Dua K. 3D-printing: An emerging and a revolutionary technology in pharmaceuticals. Panminerva Medica, 2018, 60(4), 170-173. DOI: 10.23736/s0031-0808.18.03467-5
[45]Kangarshahi BM, Naghib SM, Rabiee N. 3D printing and computer-aided design techniques for drug delivery scaffolds in tissue engineering. Expert Opinion on Drug Delivery, 2024, 21(11), 1615-1636. DOI: 10.1080/17425247.2024.2409913
[46]Jain T, Goyal A, Thakur Y, Behere BD. Applications of polymers in tissue engineering - a review. 2024, 1-4. DOI: 10.1109/icbsii61384.2024.10564053
[47]Liu B, Chen K. Advances in hydrogel-based drug delivery systems. Gels, 2024, 10(4), 262. DOI: 10.3390/gels10040262
[48]Ullah M, Shah MI, Hasan MW, Khan MJ, Mustafa U, Inam M. Engineered metal nanoparticles for precision drug delivery: Pioneering the future of medicine: Mini review. Journal of the Chinese Chemical Society, 2024, 71(11), 1358-1367. DOI: 10.1002/jccs.202400179
[49]Soomherun N, Keeratihattayakorn S, Ratanavaraporn J. Optimized silk fibroin hydrogel patches for controlled transdermal cannabidiol delivery: Formulation and in vivo safety assessment. Journal of Polymer Science, 2025, 64(1), 163-180. DOI: 10.1002/pol.20250558
[50]Uttayarat P, Praphairaksit N, Kaewkum C, Charoensri K, Chuchuen N, Nimmanpipug P. Electron beam irradiation cross-linked hydrogel patches loaded with red onion peel extract for transdermal drug delivery: Formulation, characterization, cytocompatibility, and skin permeation. Gels , 2023, 9(1), 52. DOI: 10.3390/gels9010052
[51]Singpanna K, Apiratikul C, Chittasupho C, Praphairaksit N, Uttayarat P. Alpha-tocopherol-infused flexible liposomal nanocomposite pressure-sensitive adhesive: Enhancing skin permeation of retinaldehyde. Polymers, 2024, 16(20), 2930. DOI: 10.3390/polym16202930
[52]Li MF, Chen XH, Su XX, Gao WY. The preparation and evaluation of a hydrochloride hydrogel patch with an iontophoresis-assisted release of terbinafine for transdermal delivery. Gels, 2024, 10(7), 456. DOI: 10.3390/gels10070456
[53]Barbosa AI, Lima SAC, Yousef I, Reis S. Evaluating the skin interactions and permeation of alginate/fucoidan hydrogels per se and associated with different essential oils. Pharmaceutics, 2023, 15(1), 190. DOI: 10.3390/pharmaceutics15010190
[54]Chelu M. Hydrogels with essential oils: Recent advances in designs and applications. Gels, 2024, 10(10), 636. DOI: 10.3390/gels10100636
[55]Hassan AS, Hofni A, Abourehab MAS, Abdel-Rahman IAM. Ginger extract-loaded transethosomes for effective transdermal permeation and anti-inflammation in rat model. International Journal of Nanomedicine, 2023, 1259-1280. DOI: 10.2147/ijn.s400604
[56]Shu Y, Xue R, Gao Y, Zhang W, Wang J. A thermo-responsive hydrogel loaded with an ionic liquid microemulsion for transdermal delivery of methotrexate. Journal of Materials Chemistry B, 2023, 11(24), 5494-5502. DOI: 10.1039/d2tb02189g
[57]Cheng A, Zhang SH, Meng FD, Xing MZ, Liu H, Yang GZ, et al. Nanosuspension-loaded dissolving microneedle patches for enhanced transdermal delivery of a highly lipophilic cannabidiol. International Journal of Nanomedicine, 2024, 19, 4061-4079. DOI: 10.2147/ijn.s452207
[58]Jirole UD, Asewar SS, Nagre PA, Puri SS. Microneedles : A smart approach for transdermal drug delivery system. International Journal of Scientific Research in Science and Technology, 2023, 612-623. DOI: 10.32628/ijsrst2310165
[59]Wang YH, Chen Z, Davis B, Lipman W, Xing SC, Zhang L, et al. Digital automation of transdermal drug delivery with high spatiotemporal resolution. Nature Communications, 2024, 15, 511. DOI: 10.1038/s41467-023-44532-0
[60]Guillot AJ, Martínez‐Navarrete M, Zinchuk‐Mironova V, Melero A. Microneedle‐assisted transdermal delivery of nanoparticles: Recent insights and prospects. Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, 2023, 15(4), e1884. DOI: 10.1002/wnan.1884
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Copyright (c) 2026 Suryanarayana Regulagadda, Thrimurthulu Gode, V. S.A. Pavan Rudhrabatla, Taraka Rama Prasadu Vasa, Shiva Reddy Padigapaty, Lakshmi Prasanna Nalluri (Author)
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