ADVANCED DRUG DELIVERY SYSTEM FOR IMPROVING HERBAL COMPOUND BIOAVAILABILITY AND TARGET DELIVERY

Nanotechnology has emerged as a highly progressive scientific approach in the 21st century. By exploring its association with biomedical sciences, particularly its influence on bioavailability, major developments and current limitations in this domain have been identified. The use of nanotechnology to investigate and enhance the bioavailability of herbal medicines is gaining significant attention. Present evidence shows that nanotechnology is among the fastest-growing and most promising high-tech fields globally, contributing remarkably to the advancement of biological medicine and herbal drug delivery. When herbal compounds are converted into nanosized formulations, their absorption and therapeutic effectiveness can be significantly improved. This has paved the way for the evolution of nano-herbal medicines with superior bioavailability, marking a new milestone in herbal drug innovation. Future breakthroughs are expected through the nano-formulation of key phytochemicals such as nanocurcumin, nanopiperine, nanoberberine, and others.

• Bhalani et al., 2022 Bhalani, D. V., Patel, K. R., Shah, N. K., & Shah, S. R. (2022). Bioavailability enhancement techniques for poorly aqueous soluble herbal compounds: A comprehensive review. Journal of Drug Delivery and Therapeutics, 12(3): 1–10. https://doi.org/10.22270/jddt.v12i3.5371
• Ameta et al., 2023 Ameta, R. K., Singh, P., & Verma, S. (2023). Recent advances in improving the bioavailability of herbal bioactives using emulsion-forming delivery systems. Pharmaceutics, 15(1): 1–25. https://doi.org/10.3390/pharmaceutics15010052
• Kathole, K. S., Hatwar, P. R., Bakal, R. L., & Karule, V. G. (2025). Nanotechnology-based drug delivery systems and herbal medicine. Journal of Drug Delivery & Therapeutics, 15(3): 133-141. https://doi.org/10.22270/jddt.v15i3.7017
• Devi, V. K. (2010). Importance of novel drug delivery systems in herbal medicines. Pharmacognosy Reviews, 4(7): 27–35.
• Obeid, M. A., & colleagues. (2017). Delivering natural products and biotherapeutics to improve bioavailability: strategies and challenges. Therapeutic Delivery, 8(10): 809–827. https://doi.org/10.4155/tde-2017-0060
• Balkrishna, A., Sharma, N., Srivastava, D., Kukreti, A., Srivastava, S., & Arya, V. (2024). Exploring the safety, efficacy, and bioactivity of herbal medicines: Bridging tradițional wisdom and modern science in healthcare. Future Integrative Medicine, 3(1): 35-49. https://doi.org/10.14218/FIM.2023.00086
• Sharma, A., Gupta, P. K., & Garg, S. (2022). Nano-herbal formulations: Bridging traditional phytomedicine with modern nanotechnology for improved therapeutic efficacy. Journal of Drug Delivery Science and Technology, 75: 103576. https://doi.org/10.1016/j.jddst.2021.103576
• Rai, M., Ingle, A. P., & Pandit, R. (2020). Nanotechnology-based herbal formulations for improved bioavailability and therapeutic outcomes. Phytomedicine, 76: 153259.
• Chaudhuri, B., Singh, N., & Ghosh, D. (2021). Passive and active targeting strategies for herbal nano-pharmaceuțicals: Enhancing therapeutic precision and minimizing systemic toxicity. Journal of Ethnopharmacology, 279: 114372. https://doi.org/10.1016/j.jep.2021.114372
• Zhao, J., & Zhang, M. (2019). Factors affecting the oral bioavailability of herbal compounds and strategies for improvement. Phytotherapy Research, 33(3): 566-583. file:///mnt/data/srush%20new.pdf
• Zhang, M., lin, S., & li, J. (2020). Solubility limitations of herbal phytochemicals and their impact on oral absorption: Mechanisms and enhancement strategies. Journal of Ethnopharmacology, 259: 112944. https://doi.org/10.1016/j.jep.2020.112944
• Li, C., & Chen, X. (2019). Degradation of herbal phytochemicals in the gastrointestinal tract: Implications for oral bioavailability and therapeutic efficacy. Phytotherapy Research, 33(8): 2073-2085. https://doi.org/10.1002/ptr.6394
• Yuan, J., Guo, W., & Yang, L. (2020). Role of P-glycoprotein and intestinal efflux transporters in limiting oral bioavailability of herbal constituents. Drug Metabolism and Disposition, (483): 165-178. https://doi.org/10.1124/dmd.119.089672
• Bie, B., Sun, C., & Guo, M. (2022). Food-herb interactions: Effects of dietary proteins, fibers and polyphenols on dissolution and absorption of herbal bioactives. Food & Function, 13(5): 2511-2524. https://doi.org/10.1039/D1FO03462K
• Jiang, T., & li, X. (2021). Influence of particle size, dispersion, and formulation properties on dissolution and bioavailability of herbal powders and decoctions. Drug Development and Industrial Pharmacy, (474): 567-577. https://doi.org/10.1080/03639045.2021 .1873141
• Khurana, R., Singh, S., & Singh, A. (2021). Nanocarrier-based delivery of herbal bioactives: A systematic review, Pharmaceutics, 13(11): 1798. https://doi.org/10.3390/pharmaceutics13111798
• Kesarwani, K., Gupta, R., & Rawat, A. K. S. (2013). Bioavailability enhancers of herbal origin: An overview. Pharmacognosy Reviews, (714): 121–126. https://doi.org/10.4103/0973-7847 .120522
• Moghimipour, E., Ameri, A., & Handali, S. (2015). Absorption-enhancing effects of bile salts. Molecules, 20(8): 14451-14473. https:/doi.org/10.3390/molecules200814451
• Dash, R. N., Mohammed, H., & Humayun, M. (2015). Enhanced solubility and dissolution rate of curcumin using solubilizers and co-solvent systems. Journal of Applied Pharmaceutical Science, 5(6):    28-32. https://doi.org/10.7324/JAPS.2015.50605
• Mohapatra, D., Agrawal, A. K., & Sahu, A. N. (2021). Exploring the potential of solid dispersion for improving solubility, dissolution & bioavailability of herbal extracts, enriched fractions and bioactives. Journal of Microencapsulation. https://doi.org/10.1080/02652048.2021 .1963342
• Suvarna, V. (2022). Complexation of phytochemicals with cyclodextrins and their derivatives: improving solubility, stability and bioavailability. Journal of Pharmaceutical Sciences, 1-12. https://doi.org/10.1016/j.jphs.2022.XX
• Trevaskis, N. L., Kaminskas, L. M., & Porter, C. J. H. (2007). lipid-based delivery systems and intestinal lymphatic drug transport. Advanced Drug Delivery Reviews, (598): 667-676. https://doi.org/10.1016/j.addr.2007.05.010
• Kesarwani, K., & Gupta, R. (2013). Bioavailability enhancers of herbal origin: An overview. Asian Pacific Journal of Tropical Biomedicine, 3(4):     253-266. https://doi.org/10.1016/S2221-1691(13)60061-X
• Taniguchi, C., Kawabata, Y., Wada, K., & Yamada, S. (2014). Microenvironmental pH-modification to improve dissolution behavior and oral absorption for drugs with pH-dependent solubility. Expert Opinion on Drug Delivery, I1(4): 537-548. https://doi.org/10.1517/17425247.2014.881798
• Chavan, A. K., & Tatiya, A. U. (2025). Approaches to enhance bioavailability of herbal medicines using novel carrier systems. Pharmacognosy Research, (171): 1-10. https://doi.org/10.4103/0974-8490
• Patra, J. K., Das, G., Fraceto, L. F., Campos, E. V. R., Rodriguez-Torres, M. D. P., Acosta-Torres, L. S., Diaz-Torres, L. A., Grillo, R., Swamy, M. K., Sharma, S., Habtemariam, S., & Shin, H.-S. (2018). Nano based drug delivery systems: Recent developments and future prospects for herbal medicine. Journal of Nanobiotechnology, 16(1):       1-36. https://doi.org/10.1186/s12951-018-0392-y
• Cheng, X., Wei, Y., He, M., & Xie, J. (2022). Liposomes as multifunctional nano-carriers for medicinal natural products and their derivatives. Pharmaceutics, 14(3): 563. https://doi.org/10.3390/pharmaceutics14030563
• Gaikwad, A. R., Ahire, K. D., Gosavi, A. A., Salunkhe, K. S., & Khalkar, A. (2021). Phytosome as a novel drug delivery system for bioavailability enhancement of phytoconstituents and its applications: A review. Journal of Drug Delivery & Therapeutics, 11(3): 138-152. https://doi.org/10.22270/jddt.vlli34847
• Singh, G., Pai, R. S., & Devi, K. (2020). Polymeric nanoparticles for herbal drug delivery: A comprehensive review. Journal of Drug Delivery Science and Technology, 57: 101634. https://doi.org/10.1016/j.jddst.2020.101634
• Khurana, S., Bedi, P. M. S., & Jain, N. K. (2013). Development of nanostructured lipid carriers for controlled delivery of quercetin using Box–Behnken statistical design. Drug Development and Industrial Pharmacy, 40(5): 726–737. https://doi.org/10.3109/03639045.2013.794408
• Singh, G., Pai, R. S., & Devi, K. (2020). Polymeric nanoparticles for herbal drug delivery: A comprehensive review. Journal of Drug Delivery Science and Technology, 57: 101634. https://doi.org/10.1016/j.jddst.2020.101634
• Shakeel, F., Haq, N., El-Badry, M., Alanazi, F. K., Alsarra, I. A., & Mohsin, K. (2014). Nanoemulsions as vehicles for transdermal delivery of aceclofenac: Stability, skin permeation, rheology and thermal behavior. Journal of Molecular Liquids, 198: 255–263. https://doi.org/10.1016/j.molliq.2014.06.028
• Kesharwani, P., Jain, K., & Jain, N. K. (2014). Dendrimer nanocarriers for enhanced anticancer drug therapeutics. Advanced Drug Delivery Reviews, 66: 48–68. https://doi.org/10.1016/j.addr.2013.11.004
• Pandey, A., & Dey, R. (2021). Nanocarrier -based herbal formulations: Future of phytomedicine. Pharmaceutics, 13(2): 1-21. https://doi.org/10.3390/pharmaceutics13020157
• Tewabe, P. A., Shiferaw, H., Getnet, F., & Bezabh, M. (2021). Targeted drug delivery-From magic bullet to nanomedicine. Frontiers in Pharmacology, 12:        1-18. https://doi.org/10.3389/fphar.2021.723313
• Bazak, R., Houri, M., El Achy, S., Kamel, S., & Refaat, T. (2014). Passive targeting of nanoparticles to cancer. Pharmacological Research, 69(1):      131-143. https://doi.org/10.1016/j.phrs.2012.12.006
• Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & langer, R. (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2(12): 751-760. https://doi.org/10.1038/nnano.2007.387
• Ji, T., Zhao, Y., Ding, Y., Wang, J., Zhao, R., Iang, J., & Shi, J. (2021). Responsive and activatable nanomedicines for targeted therapy. Advanced Drug Delivery Reviews, 178: 113902. https://doi.org/10.1016/j.addr.2021.113902
• Guo, J., Ping, Q., Sun, M., & Chen, Z. (2013). Smart drug delivery systems based on stimuli-responsive nanomaterials: A review. Journal of Controlled Release, 172(2): 602-617. https://doi.org/10.1016/j.jconrel.2013.06 .003
• Rautio, J., Meanwell, N. A., Di, L., & Hageman, M. J. (2018). The expanding role of prodrugs in contemporary drug design and development. Nature Reviews Drug Discovery, (178): 559-587. https://doi.org/10.1038/nrd.2018.46
• Huttunen, K. M., Raunio, H., & Rautio, J. (2011). Prodrugs-from serendipity to rational design. Pharmacological Reviews, 63(3): 750-771. https://doi.org/10.1124/pr.110.003459
• Daniels, T. R., Delgado, T., Helguera, G., Penichet, M. Į. (2012). The transferrin receptor as a targeting strategy for brain drug delivery. Pharmaceutical Research, 29(5): 1347-1358. https://doi.org/10.1007/s11095-012-0715-X
• Xia, W., & Low, P. S. (2010). Folate-targeted therapies for cancer. Journal of Medicinal Chemistry, 53(19): 6811–6824. https://doi.org/10.1021/jm100509v
• Tzeng, S. Y., & Green, J.J. (2013). Therapeutic nanomedicine: Activity and mechanisms of localization in the tumour microenvironment. Nanomedicine: Nanotechnology, Biology and Medicine, 9(5): 709-721. https://doi.org/10.1016/j.nano.2013.05 .002
• Shapiro, B., Kulkarni, S., Nacev, A., Muro, S., Sridhar, S., & Alexeev, A. (2015). Open challenges in magnetic drug targeting. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, (73): 445-477. https://doi.org/10.1002/wnan.1311
• Escoffre, J.-M., & Bouakaz, A. (2016). Therapeutic ultrasound. Advanced Drug Delivery Reviews, 72: 3-14. https://doi.org/10.1016/j.addr.2013.05.003
• li, L., ten Hagen, T. Į. M., Hossann, M., Süss, R., van Rhoon, G. C., Eggermont, A. M. M., & Haemmerich, D. (2013). Mild hyperthermia triggered drug delivery from thermosensitive liposomes using high intensity focused ultrasound. Journal of Controlled Release, 168(2): 142-150. https://doi.org/10.1016/j.jconrel.2013.02.020
• Torchilin, V. P. (2014). Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nature Reviews Drug Discovery, 13(11): 813-827. https://doi.org/10.1038/nrd4333
• Rosenblum, D., Joshi, N., Tao, W., Karp, J. M., & Peer, D. (2018). Progress and challenges towards targeted delivery of cancer therapeutics. Nature Communications, (91): 1410. https://doi.org/10.1038/s41467-018-03705-y
• Zhang, Y., Yang, H., Yang, L., & Chen, H.(2021). Artificial intelligence in nanomedicine: Opportunities and challenges for drug delivery. Advanced Drug Delivery Reviews, 178: 113923. https://doi.org/10.1016/j.addr.2021.113923
• Jalili, A., Bagherifar, R., Nokhodchi, A., Conway, B., & Javadzadeh, Y. (2023). Current advances in nanotechnology-mediated delivery of herbal and plant-derived medicines. Advanced Pharmaceutical Bulletin, 13(4): 712-722. https://doi.org/10.34172/apb.2023.087
• Rahman, M. A., Ali, A., Rahamathulla, M., Salam, S., Hani, U., Wahab, S., Warsi, M. H., Yusuf, M., Ali, A., Mittal, V., & Harwansh, R. K. (2023). Fabrication of sustained release curcumin-loaded solid lipid nanoparticles (Cur-SINs) as a potential drug delivery system for the treatment of lung cancer: Optimization of formulation and in vitro biological evaluation. Polymers, 15(3): 542. https://doi.org/10.3390/polym15030542
• Dai, K., Wu, J., Liu, X., Wang, S., Liu, Y., li, H., & Wang, H. (2024). Inclusion complex of quercetin with sulfobutylether-ẞ-cyclodextrin: Preparation, characterization, antioxidant and antibacterial activities and the inclusion mechanism. RSC Advances, 14(14): 9472-9481. https://doi.org/10.1039/D3RA08936C
• Sharifi-Rad. J., Quispe, C., Mahomoodally, M. F., Setzer, W. N., & Barbosa, A. M. (2021). Resveratrol-based nanoformulations as an emerging therapeutic strategy. Frontiers in Molecular Biosciences, 8, Article 649395. https://doi.org/10.3389/fmolb.2021.649395
• Shu, X., Chen, H., & Zheng, R. (2023). EGCG as a therapeutic agent: a systematic review of recent advances and challenges in nanocarrier strategies. Fronțiers in Pharmacology, 14, Article 1156972. https://doi.org/10.3389/fphar.2023 .1156972
• Li, J., Yang, L., Shen, R., et al. (2018). Self-nanoemulsifying system improves oral absorption and enhances anti-acute myeloid leukemia activity of berberine. Journal of Nanobiotechnology, 16(1): 76. https://doi.org/10.1186/s12951-018-0402-x
• Yu, X., lu, Y., Chen, J., Deng, Y., & Liu, H. (2025). Unlocking ginsenosides' therapeutic power with polymer-based delivery systems: Current applications and future perspectives. Frontiers in Pharmacology, 16, Article 1629803. https://doi.org/10.3389/fphar.2025.1629803
• Vandervoort, J., & Ludwig, A. (2014). Silymarin liposomes improve oral bioavailability of silybin and target hepatocytes and immune cells. European Journal of Pharmaceutical Sciences, 62: 1-10. https://doi.org/10.1016/j.ejps.2014.07.008
• Zafar, F., Jahan, N., & Bhatti, H. N. (2019). Increased oral bioavailability of piperine from an optimized Piper nigrum nanosuspension. Planta Medica, 85(3): 249-257. https://doi.org/10.1055/a-0759-2208
• Jalili, A., Bagherifar, R., Nokhodchi, A., Conway, B., & Javadzadeh, Y. (2023). Current advances in nanotechnology-mediated delivery of herbal and plant-derived medicines. Advanced Pharmaceutical Bulletin, 13(4): 712-722. https://doi.org/10.34172/apb.2023.087
• Manaia, E. B., Abuçafy, M. P., Chiari-Andréo, B. G., Silva, B. L., Oshiro-Junior, J. A., & Chiavacci, Į. A. (2017). Physicochemical characterization of drug nanocarriers. International Journal of Nanomedicine, 12: 4991-501l. https://doi.org/10.2147/IJN.S133832
• Gupta, V., Shukla, R., & Murdock, R. C. (2023). Dynamic light scattering and transmission electron microscopy in drug delivery: A roadmap for correct characterization of nanoparticles. Materials Horizons, 10(3): 562-569. https://doi.org/10.1039/13MH00717K
• Bhattacharjee, S. (2016). DLS and zeta potential - What they are and what they are not? Journal of Controlled Release, 235: 337-351. https://doi.org/10.1016/j.jconrel.2016.07.002
• Bhattacharjee, S. (2021). Fast and versatile analysis of liposome encapsulation efficiency by nanoparticle exclusion chromatography. Journal of Controlled Release, 330: 117–124. https://doi.org/10.1016/j.jconrel.2021.04.024
• Ribeiro, A., & Pinho, S. C. (2021). Recent progress in drug release testing methods of bio-polymeric particulate systems. Pharmaceutics, 13(8): 1313. https://doi.org/10.3390/pharmaceutics13081313
• Wadhwa, P., Sharma, S., Sahu, S., Sharma, A., & Kumar, D. (2022). A review of nanoparticles characterization techniques. Current Nanomaterials, 7(3): 255–274. https://doi.org/10.2174/2405461507666220405113715
• Jain, S., & Jain, N. K. (2023). Comprehensive characterization approaches for nanocarriers: Bridging the gap between laboratory research and clinical translation. Drug Delivery and Translational Research, 13(7): 2105–2125. https://doi.org/10.1007/s13346-023-01315-9(springer.com)
• Mohammed. A. R., Syeda, J. T., Wasan, K. M., & Wasan, E. K. (2017). An overview of chitosan nanoparticles and its role in oral drug delivery: Focus on stability issues. International Journal of Pharmaceutics,    531(1): 128–138. https://doi.org/10.1016/j.ijpharm.2017.08.080
• Kaur, P., & Kaur, M. (2021). Challenges in nanoparticle-based drug delivery: Drug loading and release kinetics. Pharmaceutical Nanotechnology, 9(4): 345–359. https://doi.org/10.2174/2211738510666210601100822
• Kumar, P., & Nanda, A. (2022). Regulatory challenges and safety considerations in the clinical translation of nanomedicines. Drug Delivery and Translational Research, 12(5): 1234–1251. https://doi.org/10.1007/s13346-022-01121-5
• Torchilin, V. P. (2021). Multifunctional, stimuli-sensitive nanoparticulate drug delivery systems: Challenges of manufacturing and cost considerations. Journal of Controlled Release, 338: 550–567. https://doi.org/10.1016/j.jconrel.2021.06.034
• Ventola, C. L. (2017). Progress in nanomedicine: FDA-approved and investigational nanodrugs.                 Pharmacy and Therapeutics, 42(12),                                  742–755. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744572/
• Singh, P., Kim, Y.J., Zhang, D., & Yang, D.C. (2023). Nanotechnology-based delivery systems for herbal therapeutics: Current trends and future perspectives. International Journal of Pharmaceutics, 648: 123987. https://doi.org/10.1016/j.ijpharm.2023.123987
• Zhao, Y., Wang, Y., & Li, P. (2021). Stimuli-responsive nanocarriers for targeted delivery of herbal therapeutics: Advances and future perspectives. Journal of Controlled Release, 336: 393–412. https://doi.org/10.1016/j.jconrel.2021.05.027
• Zhang, L., Gu, F. X., Chan, J. M., Wang, A. Z., Langer, R. S., & Farokhzad, O. C. (2008). Nanoparticles in medicine: Therapeutic applications and developments. Clinical Pharmacology & Therapeutics, 83(5): 761-769. https://doi.org/10.1038/sj.clpt.6100400
• Xu, L., Qiao, M., & Zhang, Q. (2020). Hybrid nanocarriers for targeted and controlled delivery of herbal therapeutics. Journal of Controlled Release, 328: 109–125. https://doi.org/10.1016/j.jconrel.2020.08.042
• Liu, X., Li, P., Zhang, Y., & Zhou, Y. (2021). Biodegradable and natural polymer-based nanocarriers for herbal drug delivery: Advances and perspectives. International Journal of Biological Macromolecules, 183: 1272–1288. https://doi.org/10.1016/j.ijbiomac.2021.05.023