Scientific Online Resource System

Biomedical Reviews

Nanoencapsulation: A Promising Strategy for Biomedical Applications of Ferulic Acid

Parichehr Hassanzadeh, Fatemeh Atyabi, Rassoul Dinarvand


Over the last decades, nutraceuticals and natural products have been the focus of intense research. Ferulic acid, an active phenolic constituent of many plant species with a wide-spectrum of pharmacological properties (e.g. effects against the oxidative stress, thrombosis, diabetes, aging, and neurotoxicity) has attracted a growing interest in the area of biomedical research and clinical practice. Ferulic acid is able to affect a variety of signaling pathways including those of the brain suggesting the influential role of this phytochemical on the neuroinflammatory and neurodegenerative processes as well as the neuronal survival and plasticity. However, poor solubility and physiochemical instability may negatively affect the efficiency of this ubiquitous nutraceutical. In recent years, tremendous research efforts in nanotechnology have provided highly advanced drug delivery systems for improved pharmacological profile of the therapeutic agents, targeted drug delivery, controlled release, and reduced side effects. The present review highlights the therapeutic significance of ferulic acid and the research progress regarding the development of ferulic acid-based nanoformulations. Biomed Rev 2017; 28: 22-30.

Keywords: nanotechnology, nutraceuticals, phenolic compound, phytochemical, drug delivery

Full Text


Tapsell LC, Hemphill I, Cobiac L, Patch CS, Sullivan DR, Fenech M, et al. Health benefits of herbs and spices: the past, the present, the future. Med J Aust 2006; 185: S4-S24. PMD: 17022438.

Gohil KJ, Kshirsagar SB, Sahane RS. Ferulic acid- A comprehensive pharmacology of an important bioflavonoid. Int J Pharm Sci Res 2012; 3: 700-710. DOI:10.13040/IJPSR.0975-8232.3(3).700-10.

Yan JJ, Cho JY, Kim HS, Kim KL, Jung JS, Huh SO, et al. Protection against b-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br J Pharmacol 2001; 133: 89-96. DOI:10.1038/sj.bjp.0704047.

Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy. Life Sci 2017; 179: 9-14. DOI: 10.1016/j.lfs.2016.08.011.

Cheng CY, Ho TY, Lee EJ, Su SY, Tang NY, Hsieh CL. Ferulic acid reduces cerebral infarct through its antioxidative and anti-inflammatory effects following transient focal cerebral ischemia in rats. Am J Chin Med 2008; 36: 1105-1119. DOI:10.1142/S0192415X08006570.

Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Ferulic acid-loaded nanostructured lipid carriers: A promising nanoformulation against the ischemic neural injuries. Life Sci 2017; 28. pii: S0024-3205(17)30623-9. DOI: 10.1016/j.lfs.2017.11.046.

Ou S, Kwok KC. Ferulic acid: pharmaceutical functions, preparation and applications in foods. J Sci Food Agric 2004; 84: 1261-1269. doi:10.1002/jsfa.1873.

Brenelli de Paiva L, Goldbeck R, Dantas dos Santos W, Marcio Squina F. Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field. Braz J Pharm Sci 2013; 49: 395-411.

Sudheer AR, Muthukumaran S, Kalpana C, Srinivasan M, Menon VP. Protective effect of ferulic acid on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes: a comparison with Nacetylcysteine. Toxicol In Vitro 2007; 21: 576-585. DOI:10.1016/j.tiv.2006.11.006.

Liu Y. Pharmaceutical composition for increasing immunity and decreasing side effects of anticancer chemotherapy. US patent 1987; 4,687,761.

Wang B, Ouyang J, Liu Y, Yang J, Wei L, Li K, Yang H. Sodium ferulate inhibits atherosclerogenesis in hyperlipidemia rabbits. J Cardiovasc Pharmacol 2004; 43:549-554. PMID:15085066.

Mathew S, Abraham TE. Bioconversions of ferulic acid, an hydroxycinnamic acid. Crit Rev Microbiol 2006; 32: 115-125. DOI:10.1080/10408410600709628.

Lin FH, Lin JY, Gupta RD, Tournas JA, Burch JA, Selim MA, et al. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol 2005; 125: 826-832. DOI:10.1111/j.0022-202X.2005.23768.x.

Lina CM, Chiuc JH, Wu IH, Wang BW, Pan CM, Cheng YH. Ferulic acid augments angiogenesis via VEGF, PDGF and HIF-1a. J Nutr Biochem 2010; 21: 627-633. doi: 10.1016/j.jnutbio.2009.04.001.

Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Ferulic acid-loaded nanostructured lipid carriers: A promising nanoformulation against the ischemic neural injuries. Life Sci 2016; 3205: 30623-30629. DOI: 10.1016/j.lfs.2017.11.046.

Lenzi J, Rodrigues AF, de Sousa Rós A, Blanski de Castro B, de Lima D, Delwing Dal Magro D. Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system. Metab Brain Dis 2015; 30: 1453-1463. DOI 10.1007/s11011-015-9725-6.

Zeni ALB, Zomkowski ADE, Maraschin M, Rodrigues ALS, Tasca CI. Involvement of PKA, CaMKII, PKC, MAPK/ERK and PI3K in the acute antidepressant-like effect of ferulic acid in the tail suspension test. Pharmacol Biochem Behav 2012; 103: 181-186. DOI:10.1016/j.pbb.2012.08.020.

Castren E, Voikar V, Rantamaki T. Role of neurotrophic factors in depression. Curr Opin Pharmacol 2007; 7: 18-21. DOI 10.1016/j.coph.2006.08.009.

Aloe L, Rocco ML, Balzamino BO, Micera A. Nerve growth factor: a focus on neuroscience and

therapy. Curr Neuropharmacol 2015; 13: 294-303. PMCID:PMC4812798.

Berton O, Nestler EJ. New approaches to antidepressant drug discovery: Beyond monoamines. Nat Rev Neurosci 2006; 7: 137-151. DOI:10.1038/nrn1846.

Levi-Montalcini R. The nerve growth factor and the neuroscience chess board. Prog Brain Res 2004; 146: 525-527. PMD: 14699984.

Lad SP, Neet KE, Mufson EJ. Nerve growth factor: structure, function and therapeutic implications for Alzheimer`s disease. Curr Drug Targets CNS Neurol Disord 2003; 2: 315-34. PMID:14529363.

Hassanzadeh P, Hassanzadeh A. The CB1 receptor-mediated endocannabinoid signaling and NGF: the novel targets of curcumin. Neurochem Res 2012; 37: 1112-1120. DOI 10.1007/s11064-012-0716-2.

Hassanzadeh P, Rahimpour S. The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs. Psychopharmacology 2011; 215: 129-141. DOI 10.1007/s00213-010-2120-4.

Hassanzadeh P, Hassanzadeh A. Implication of NGF and endocannabinoid signaling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential. Psychopharmacology 2013; 229: 571-578. DOI 10.1007/s00213-013-3111-z.

Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. The endocannabinoid system and NGF are involved in the mechanism of action of resveratrol: a multi-target nutraceutical with therapeutic potential in neuropsychiatric disorders. Psychopharmacology 2016; 233: 1087-1096. DOI 10.1007/s00213-015-4188-3.

Hassanzadeh P, Hassanzadeh A. Involvement of the neurotrophin and cannabinoid systems in the mechanisms of action of neurokinin receptor antagonists. Eur Neuropsychopharm 2011; 21: 905-917. DOI:10.1016/j.euroneuro.2011.01.002.

Hassanzadeh P, Hassanzadeh A. Effects of different psychotropic agents on the central nerve growth factor protein. Iran J Basic Med Sci 2010; 13: 202-209. DOI: 10.22038/ijbms.2010.5064.

Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Ferulic acid, a phenolic compound with therapeutic effects in neuropsychiatric disorders, stimulates the production of NGF and endocannabinoids in rat brain. Physiol Pharmacol 2017 (in press) URL: article-1-1265-en.html.

Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR, Duman RS. Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol Psychiatry 2007; 62: 496-504. DOI:10.1016/j.biopsych.2007.02.006.

Conner JM, Franks KM, Titterness AK, Russell K, Merrill DA, Christie BR et al. NGF is essential for hippocampal plasticity and learning. J Neurosci 2009; 29:10883-10889. PMID:19726646.

Moises HC, Womble MD, Washburn MS, Williams LR. Nerve growth factor facilitates cholinergic neurotransmission between nucleus basalis and the amygdala in rat: an electrophysiological analysis. J Neurosci 1995; 15: 8131-8142. PMID:8613748.

Miwa T, Moriizumi T, Horikawa I, Uramoto N, Ishimaru T, Nishimura T, et al. Role of nerve growth factor in the olfactory system. Microsc Res Tech 2002; 58: 197-203. DOI:10.1002/jemt.10149.

Hassanzadeh P. The edocannabinoid system: critical for the neuroptrophic action of psychotropic drugs. Biomed Rev 2010; 21: 31-46. ISSN 1314-1929.

Hassanzadeh P. Discovery of the endocannabinoid system: A breakthrough in neuroscience. Arch Neurosci 2014; 2: e15030. DOI: 10.5812/archneurosci.15030.

Hassanzadeh P, Hassanzadeh A. The role of the endocannabinoids in suppression of the hypothalamic-pituitary-adrenal axis activity by doxepin. Iran J Basic Med Sci 2011; 14: 414-421. PMCID: PMC3586843.

Viveros MP, Marco EM, File SE. Endocannabinoid system and stress and anxiety responses. Pharmacol Biochem Behav 2005; 81: 331-342. DOI:10.1016/j.pbb.2005.01.029

Bambico FR, Duranti A, Tontini A, Tarzia G, Gobbi G. Endocannabinoids in the treatment of mood disorders: evidence from animal models. Curr Pharm Des 2009; 15: 1623-1646. PMID:19442178.

Zhaohui Zhao, Mohammed H. Moghadasian. Chemistry, natural sources, dietary intake and pharmacokinetic properties of ferulic acid: A review. Food Chem 2008; 109: 691-702. doi:10.1016/j.foodchem.2008.02.039.

Patel T, Zhou J, Piepmeier JM, Saltzman WM. Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev 2012; 64: 701-705. DOI: 10.1016/j.addr.2011.12.006.

Fernandes R, Gracias DH. Self-folding polymeric containers for encapsulation and delivery of drugs. Adv Drug Deliv Rev 2012; 64: 1579-1589. DOI: 10.1016/j.addr.2012.02.012.

Sun NF, Meng QY, Tian AL, Hu SY, Wang RH, Liu ZX, et al. Nanoliposome mediated FL/TRAIL double-gene therapy for colon cancer: in vitro and in vivo evaluation. Cancer Lett 2012; 315: 69-77. DOI:10.1016/j.canlet.2011.10.010.

Joshi MD, Müller RH. Lipid nanoparticles for parenteral delivery of actives. Eur J Pharm Biopharm 2009; 71: 161-172. DOI: 10.1016/j.ejpb.2008.09.003.

Kumbhar DD, Pokharkar VB. Engineering of a nanostructured lipid carrier for the poorly water-soluble drug, bicalutamide: Physicochemical investigations. Colloids Surf A Physicochem Eng Asp 2013; 416: 32-42.

Hassanzadeh P, Atyabi F, Dinarvand R, Dehpour AR, Azhdarzadeh M, Dinarvand M. Application of nanostructured lipid carriers: The prolonged protective effects for sesamol in in vitro and in vivo models of ischemic stroke via activation of PI3K signalling pathway. Daru Int J Pharm 2017; (in press).

Hassanzadeh P. Nanopharmaceuticals: Innovative theranostics for the neurological disorders. Biomed Rev 2014; 25: 25-34. DOI: 10.14748/bmr.v25.1043.

Jose Merlin JP, Rajendra Prasad N, Shibli SMA, Sebeela M . Ferulic acid loaded Poly-d,l-lactide-co-glycolide nanoparticles: Systematic study of particle size, drug encapsulation efficiency and anticancer effect in nonsmall cell lung carcinoma cell line in vitro. Biomed Prevent Nutr 2012; 2: 69-76.

Vashisth P, Kumar N, Sharma M, Pruthi V. Biomedical applications of ferulic acid encapsulated electrospun nanofibers. Biotech Rep 2015: 8: 36-44.

Vashisth P, Sharma M, Nikhil K, Singh H, Panwar R, Pruthi PA, Pruthi V. Antiproliferative activity of ferulic acid-encapsulated electrospun PLGA/PEO nanofibers against MCF-7 human breast carcinoma cells. Biotechnology 2015; 5: 303-315. DOI 10.1007/s13205-014-0229-6.

Kim HJ, Ryu K, Kang JH, Choi AJ, Kim T, Oh JM. Anticancer activity of ferulic acid-inorganic nanohybrids synthesized via two different hybridization routes, reconstruction and exfoliation-reassembly. Sci World J 2013; 2013: Article ID 421967.

Panwar R, Pemmaraju SC, Sharma AK, Pruthi V. Efficacy of ferulic acid encapsulated chitosan nanoparticles against Candida albicans biofilm. Microb Pathogen 2016; 95: 21e31. DOI: 10.1016/j.micpath.2016.02.007.

Wu W, Lee SY, Wu X, Tyler JY, Wang H, Ouyang Z, et al. Neuroprotective ferulic acid (FA)eglycol chitosan (GC) nanoparticles for functional restoration of traumatically injured spinal cord. Biomaterials 2014; 35: 2355e2364. DOI:10.1016/j.biomaterials.2013.11.074.

Ratih P, Kim SK. Neuroprotective properties of chitosan and its derivatives. Marine Drugs 2010; 8: 2117-2128. [PubMed: 20714426].

Na JH, Lee SY, Lee S, Koo H, Min KH, Jeong SY, Yuk SH, et al. Effect of the stability and deformability of self assembled glycol chitosan nanoparticles on tumor- targeting efficiency. J Control Release 2012; 163: 2-9. [PubMed: 22846988].

Wu W, Lee SY, Wu X, Tyler JY, Wang H, Ouyang Z, et al. Neuroprotective ferulic acid (FA)-glycol chitosan (GC) nanoparticles for functional restoration of traumatically injured spinal cord. Biomaterials 2014; 35: 2355-2364. doi : 10.1016/j.biomaterials.2013.11.074.

Zhang Y, Li Z, Zhang K, Yang G, Wang Z, Zhao J, et al. Ethyl oleate-containing nanostructured lipid carriers improve oral bioavailability of trans-ferulic acid ascompared with conventional solid lipid nanoparticles. Int J Pharm 2016; 511: 57-64. DOI: 10.1016/j.ijpharm.2016.06.131.

Dzenis Y. Spinning continuous fibres for nanotechnology. Science 2004; 304: 1917-1919. DOI: 10.1126/science. 1099074

Yua DG, Yangb JM, Branford-Whitec C, Lub P, Zhangb L, Zhu LM. Third generation solid dispersions of ferulic acid in electrospun composite nanofibers. Int J Pharm 2010; 400: 158-164. DOI:10.1016/j.ijpharm.2010.08.010.

Wu XM, Branford-White C, Yu DG, Chatterton NP, Zhu LM. Preparation of core-shell PAN nanofibers encapsulated α-tocopherol acetate and ascorbic acid 2-phosphate for photoprotection. Colloids Surf B: Biointerfaces 2011; 82: 247-252. DOI: 10.1016/j.colsurfb.2010.08.049.

Yanga JM, Zha LS, Yub DG, Liu J. Coaxial electrospinning with acetic acid for preparing ferulic acid/zein composite fibers with improved drug release profiles. Colloids Surf B: Biointerfaces 2013; 102: 737- 743. DOI: 10.1016/j.colsurfb.2012.09.039.

Garcea G, Dennison AR, Steward WP, Berry DP. Role of inflammation in pancreatic carcinogenesis and the implications for future therapy. Pancreatology 2005; 5: 514-529. DOI:10.1159/000087493.

DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics. Cancer J Clin 2014; 64: 252-271. DOI: 10.3322/caac.21235.

Thakkar A, Chenreddy S, Wang J, Prabhu S. Ferulic acid combined with aspirin demonstrates chemopreventive potential towards pancreatic cancer when delivered using chitosanA‘coated solidA‘lipid nanoparticles. Cell Biosci 2015; 5: 46. DOI 10.1186/s13578-015-0041-y.

Fonte P, Andrade F, Araujo F, Andrade C, Neves J, Sarmento B. Chitosan coated solid lipid nanoparticles for insulin delivery. Methods Enzymol 2012; 508: 295-314. DOI: 10.1016/B978-0-12-391860-4.00015-X.

Agrawal A, Cha-Molstad H, Samols D, Kushner I. Overexpressed nuclear factor-κB can participate in endogenous C-reactive protein induction, and enhances the effects of C/EBPβ and signal transducer and activator of transcription-3. Immunology 2003; 108: 539-547. PMCID:PMC1782914.

Kim HJ, Hawke N, Baldwin AS. NF-kappaB and IKK as therapeutic targets in cancer. Cell Death Differ 2006; 13: 738-747. DOI:10.1038/sj.cdd.4401877.

Hassanzadeh P. Colorectal cancer and NF-κB signaling pathway. Gastroenterol Hepatol Bed Bench 2011; 4: 127-132. PMID:24834170.

Müller RH, Shegokar R, Keck CM. 20 Years of lipid nanoparticles (SLN &NLC): present state of development and industrial application. Curr Drug Discov Technol 2011; 8: 207-227. PMID:21291409.

Martins S, Tho I, Reimold I, Fricker G, Souto E, Ferreira D, Brandl M. Brain delivery of camptothecin by means of solid lipid nanoparticles: formulation design, in vitro and in vivo studies. Int J Pharm 2012; 439: 49-62. DOI: 10.1016/j.ijpharm.2012.09.054.

Bondi M, Montana G, Craparo E, Picone P, Capuano G, Carlo MD, et al. Ferulic acid-loaded lipid nanostructures as drug delivery systems for Alzheimer`s disease: Preparation, characterization and cytotoxicity studies. Curr Nanosci 2009; 5: 26-32. DOI: 10.2174/157341309787314656.

Fetoni AR, Mancuso C, Eramo SL, Ralli M, Piacentini R, Barone E, et al. In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea-pig. Neuroscience 2010; 169: 1575-1588. doi: 10.1016/j.neuroscience.2010.06.02.

Trombino S, Cassano R, Ferrarelli T, Barone E, Picci N, Mancuso C. Trans-ferulic acid-based solid lipid nanoparticles and their antioxidant effect in rat brain microsomes. Colloids Surf B Biointerfaces 2013; 109: 273-279. DOI: 10.1016/j.colsurfb.2013.04.005.

Kaur IP, Bhandari R, Bhandari S, Kakkar V. Potential of solid lipid nanoparticles in brain targeting. J Control Release 2008; 127: 97-109. DOI: 10.1016/j.jconrel.2007.12.018.

Dhuria SV, Hanson LR, Frey WH 2nd. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci 2010; 99: 1654-1673. DOI: 10.1002/jps.21924.

Carbone C, Campisi A, Musumeci T, Raciti G, Bonfanti R, Puglisi G. FA-loaded lipid drug delivery systems: Preparation, characterization and biological studies. Eur J Pharm Sci 2014; 52:12-20.

Serafim TL, Carvalho FS, Marques MP, Calheiros R, Silva T, Garrido J, et al. Lipophilic caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells. Chem Res Toxicol 2011; 24: 763-774. DOI: 10.1021/tx200126r.

Karthikeyan S, Kanimozhi G, Prasad NR, Mahalakshmi R. Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro. Toxicol In Vitro 2011; 25: 1366-1375. DOI: 10.1016/j.tiv.2011.05.007.

Bandugula VR, Rajendra Prasad N. 2-Deoxy-d-glucose and ferulic acid modulates radiation response signaling in non-small cell lung cancer cells. Tumour Biol 2013; 34: 251-259. doi: 10.1007/s13277-012-0545-6.

Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advantages in neurooncology: the avenue to a cure for malignant glioma. Cancer J Clin 2010; 60:166-193. DOI: 10.3322/caac.20069.

Hassanzadeh P, Arbabi E, Rostami F, Atyabi F, Dinarvand R. aerosol delivery of ferulic acid-loaded nanostructured lipid carriers: A promising therapeutic approach against the lung disorders. Physiol Pharmacol 2017 (in press) URL:

Hassanzadeh P. Computational modelling: Moonlighting on the neuroscience and medicine. Biomed Rev 2013; 24: 25-31. DOI: 10.14748/bmr.v24.19.

Hassanzadeh P, Atyabi F, Dinarvand R. Application of modelling and nanotechnology-based approaches: The emergence of breakthroughs in theranostics of central nervous system disorders. Life Sci 2017; 182: 93-103. DOI: 10.1016/j.lfs.2017.06.001.



Article Tools
Email this article (Login required)
About The Authors

Parichehr Hassanzadeh
Tehran University of Medical Sciences, Tehran
Iran, Islamic Republic of

Nanotechnology Research Center, Faculty of Pharmacy

Fatemeh Atyabi
Tehran University of Medical Sciences, Teheran
Iran, Islamic Republic of

Department of Pharmaceutics, Faculty of Pharmacy

Rassoul Dinarvand
Tehran University of Medical Sciences, Teheran
Iran, Islamic Republic of

Department of Pharmaceutics, Faculty of Pharmacy

Font Size