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Review

Recent expansions of novel strategies towards the drug targeting into the brain

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Pages 5895-5909 | Published online: 30 Jul 2019

References

  • Parent AC. M.B. Carpenter’s Human Neuroanatomy. Michigan: Williams & Wilkins; 1995.
  • Cosgrove KP, Mazure CM, Staley JK. Evolving knowledge of sex differences in brain structure, function, and chemistry. Biol Psychiatry. 2007;62(8):847–855. doi:10.1016/j.biopsych.2007.03.00117544382
  • Patel MM, Patel BM. Crossing the blood-brain barrier: recent advances in drug delivery to the brain. CNS Drugs. 2017;31(2):109–133. doi:10.1007/s40263-016-0405-928101766
  • Nagpal K, Singh SK, Mishra DN. Drug targeting to brain: a systematic approach to study the factors, parameters and approaches for prediction of permeability of drugs across BBB. Expert Opin Drug Deliv. 2013;10(7):927–955. doi:10.1517/17425247.2013.76235423330786
  • Lu CT, Zhao YZ, Wong HL, Cai J, Peng L, Tian XQ. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int J Nanomedicine. 2014;9(1):2241–2257. doi:10.2147/IJN.S6128824872687
  • Odiba A, Ottah V, Ottah C, et al. Therapeutic nanomedicine surmounts the limitations of pharmacotherapy. Open Med. 2017;12:271–287. doi:10.1515/med-2017-0041
  • Agrahari V, Agrahari V, Mitra AK. Nanocarrier fabrication and macromolecule drug delivery: challenges and opportunities. Ther Deliv. 2016;7(4):257–278.27010987
  • Banks WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discovery. 2016;15(4):275–292.26794270
  • Gao H. Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharmaceutica Sinica B. 2016;6(4):268–286.27471668
  • Reeve A, Simcox E, Turnbull D. Ageing and Parkinson’s disease: why is advancing age the biggest risk factor?. Ageing Res Rev. 2014;14:19–30. doi:10.1016/j.arr.2014.01.00424503004
  • Neuwelt E, Abbott NJ, Abrey L, et al. Strategies to advance translational research into brain barriers. Lancet Neurol. 2008;7(1):84–96. doi:10.1016/S1474-4422(07)70326-518093565
  • Pardridge WM. Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv. 2003;3(2):90–105, 151. doi:10.1124/mi.3.2.9014993430
  • Chen Y, Liu L. Modern methods for delivery of drugs across the blood–brain barrier. Adv Drug Deliv Rev. 2012;64(7):640–665. doi:10.1016/j.addr.2011.11.01022154620
  • Pardridge WM. Drug transport in brain via the cerebrospinal fluid. Fluids Barriers CNS. 2011;8(1):7. doi:10.1186/2045-8118-8-721349155
  • de Boer AG, Gaillard PJ. Drug targeting to the brain. Annu Rev Pharmacol Toxicol. 2007;47:323–355. doi:10.1146/annurev.pharmtox.47.120505.10523716961459
  • Terasaki T, Tsuji A. Drug delivery to the brain utilizing blood-brain barrier transport systems. J Controlled Release. 1994;29(1):163–169. doi:10.1016/0168-3659(94)90132-5
  • Fischer H, Gottschlich R, Seelig A. Blood-brain barrier permeation: molecular parameters governing passive diffusion. J Membr Biol. 1998;165(3):201–211.9767674
  • Garg T, Bhandari S, Rath G, Goyal AK. Current strategies for targeted delivery of bio-active drug molecules in the treatment of brain tumor. J Drug Target. 2015;23(10):865–887. doi:10.3109/1061186X.2015.102993025835469
  • Jones AR, Shusta EV. Blood-brain barrier transport of therapeutics via receptor-mediation. Pharm Res. 2007;24(9):1759–1771. doi:10.1007/s11095-007-9379-017619996
  • Wang YY, Lui PC, Li JY. Receptor-mediated therapeutic transport across the blood-brain barrier. Immunotherapy. 2009;1(6):983–993. doi:10.2217/imt.09.7520635914
  • Lajoie JM, Shusta EV. Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier. Annu Rev Pharmacol Toxicol. 2015;55:613–631. doi:10.1146/annurev-pharmtox-010814-12485225340933
  • Mena I, Cotzias GC. Protein intake and treatment of Parkinson’s disease with levodopa. N Engl J Med. 1975;292(4):181–184. doi:10.1056/NEJM1975012329204041109209
  • Simard AR, Rivest S. Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia. FASEB J. 2004;18(9):998–1000. doi:10.1096/fj.04-1517fje15084516
  • Priller J, Flugel A, Wehner T, et al. Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med. 2001;7(12):1356–1361. doi:10.1038/nm1201-135611726978
  • Tong HI, Kang W, Davy PM, et al. Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System. PLoS One. 2016;11(4):e0154022. doi:10.1371/journal.pone.015402227115998
  • Arora W. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int J Nanomedicine. 2012;7:3445–3471. doi:10.2147/IJN.S3032022848170
  • Batrakova EV, Gendelman HE, Kabanov AV. Cell-mediated drug delivery. Expert Opin Drug Deliv. 2011;8(4):415–433. doi:10.1517/17425247.2011.55945721348773
  • Bay DC, Turner RJ. Small Multidrug Resistance Efflux Pumps In: Li X-Z, Elkins CA, Zgurskaya HI, editors. Efflux-Mediated Antimicrobial Resistance in Bacteria: Mechanisms, Regulation and Clinical Implications. Cham: Springer International Publishing; 2016:45–71.
  • Golden PL, Pollack GM. Blood-brain barrier efflux transport. J Pharm Sci. 2003;92(9):1739–1753. doi:10.1002/jps.1042412949994
  • Qosa H, Miller DS, Pasinelli P, Trotti D. Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders. Brain Res. 2015;1628(Pt B):298–316. doi:10.1016/j.brainres.2015.07.00526187753
  • Loscher W, Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005;2(1):86–98. doi:10.1602/neurorx.2.1.8615717060
  • Miller DS, Bauer B, Hartz AM. Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve central nervous system pharmacotherapy. Pharmacol Rev. 2008;60(2):196–209. doi:10.1124/pr.107.0710918560012
  • Abbott NJ, Romero IA. Transporting therapeutics across the blood-brain barrier. Mol Med Today. 1996;2(3):106–113.8796867
  • Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000;97(7):3473–3478. doi:10.1073/pnas.05058539710716719
  • Demeule M, Regina A, Jodoin J, et al. Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood-brain barrier. Vascul Pharmacol. 2002;38(6):339–348.12529928
  • Alexander A, Saraf S, Saraf S, et al. Amalgamation of stem cells with nanotechnology: A unique therapeutic approach. Curr Stem Cell Res Ther. 2018;14(2):83–92.
  • Agrawal M, Saraf S, Saraf S, et al. Recent advancements in the field of nanotechnology for the delivery of anti-Alzheimer drug in the brain region. Expert Opin Drug Deliv. 2018;15(6):589–617. doi:10.1080/17425247.2018.147105829733231
  • Khare S, Ajazuddin AA, Amit. N. Biomedical applications of nanobiotechnology for drug design, delivery and diagnostics. Res J Pharm Technol. 2014;7(8):915–925.
  • Jane B. Reece, Martha R. Taylor, Eric J. Simon, Jean L. Dickey.Campbell Biology—Concepts and Connections. North Carolina: Pearson Education; 2009.
  • Alexander A, Saraf S, Saraf S. A comparative study of chitosan and poloxamer based thermosensitive hydrogel for the delivery of PEGylated melphalan conjugates. Drug Dev Ind Pharm. 2015;41(12):1954–1961. doi:10.3109/03639045.2015.101116725678314
  • Agrawal M, Tripathi DK, Saraf S, et al. Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer’s disease. J Controlled Release. 2017;260:61–77. doi:10.1016/j.jconrel.2017.05.019
  • Pedro Ramos-Cabrer FC. Liposomes and nanotechnology in drug development: focus on neurological targets. Int J Nanomedicine. 2012;8(1):951–960.
  • Salade L, Wauthoz N, Deleu M, et al. Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia. Int J Nanomedicine. 2017;13:8531–8543.
  • Szebeni J, Baranyi L, Savay S, et al. Role of complement activation in hypersensitivity reactions to doxil and hynic PEG liposomes: experimental and clinical studies. J Liposome Res. 2002;12(1–2):165–172. doi:10.1081/LPR-12000479012604051
  • Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):102. doi:10.1186/1556-276X-8-10223432972
  • Débora B, Vieira LFG. Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier. Int J Nanomedicine. 2016;11:5381–5414. doi:10.2147/IJN.S11721027799765
  • Hofheinz RD, Gnad-Vogt SU, Beyer U, Hochhaus A. Liposomal encapsulated anti-cancer drugs. Anticancer Drugs. 2005;16(7):691–707.16027517
  • Barbara Kneidl MP, Winter G, Lindner LH, Hossann M. Thermosensitive liposomal drug delivery systems: state of the art review. Int J Nanomedicine. 2014;9(1):4387–4398. doi:10.2147/IJN.S4929725258529
  • Callum Ross MT, Fullwood N, Allsop D. Liposome delivery systems for the treatment of Alzheimer’s disease. Int J Nanomedicine. 2018;13:8507–8522. doi:10.2147/IJN.S18311730587974
  • Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975–999. doi:10.2147/IJN.S6886125678787
  • Ross C, Taylor M, Fullwood N, Allsop D. Liposome delivery systems for the treatment of Alzheimer’s disease. Int J Nanomedicine. 2018;13:8507–8522. doi:10.2147/IJN.S18311730587974
  • Zheng X, Shao X, Zhang C, et al. Intranasal H102 peptide-loaded liposomes for brain delivery to treat Alzheimer’s disease. Pharm Res. 2015;32(12):3837–3849. doi:10.1007/s11095-015-1744-926113236
  • Al Asmari AK, Ullah Z, Tariq M, Fatani A. Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil. Drug Des Devel Ther. 2016;10:205–215. doi:10.2147/DDDT.S93937
  • Xiao W, Fu Q, Zhao Y, et al. Ascorbic acid-modified brain-specific liposomes drug delivery system with “lock-in” function. Chem Phys Lipids. 2019. doi:10.1016/j.chemphyslip.2019.01.005
  • Li X, Xiao H, Lin C, et al. Synergistic effects of liposomes encapsulating atorvastatin calcium and curcumin and targeting dysfunctional endothelial cells in reducing atherosclerosis. Int J Nanomedicine. 2019;14:649–665. doi:10.2147/IJN.S18981930697048
  • Kuo YC, Chen CL, Rajesh R. Optimized liposomes with transactivator of transcription peptide and anti-apoptotic drugs to target hippocampal neurons and prevent tau-hyperphosphorylated neurodegeneration. Acta Biomater. 2019;87:207–222. doi:10.1016/j.actbio.2019.01.06530716553
  • Batista CA, Larson RG, Kotov NA. Nonadditivity of nanoparticle interactions. Science (New York, NY). 2015;350(6257):1242477. doi:10.1126/science.1242477
  • Hoshyar N, Gray S, Han H, Bao G. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine (London, England). 2016;11(6):673–692. doi:10.2217/nnm.16.5
  • Schmalz G, Hickel R, van Landuyt KL, Reichl FX. Nanoparticles in dentistry. Dental Mater. 2017;33(11):1298–1314. doi:10.1016/j.dental.2017.08.193
  • Dwivedi GR, Singh DP, Sharma A, Darokar MP, Srivastava SK. Nano particles: emerging warheads against bacterial superbugs. Curr Top Med Chem. 2016;16(18):1963–1975.26876525
  • Abrahamse H, Kruger CA, Kadanyo S, Mishra A. Nanoparticles for advanced photodynamic therapy of cancer. Photomed Laser Surg. 2017;35(11):581–588.28937916
  • Portioli C, Bovi M, Benati D, et al. Novel functionalization strategies of polymeric nanoparticles as carriers for brain medications. J Biomed Mater Res Part A. 2017;105(3):847–858.
  • Alexander A, Ajazuddin KJ, Saraf S, Saraf S. Poly(ethylene glycol)-poly(lactic-co-glycolic acid) based thermosensitive injectable hydrogels for biomedical applications. J Controlled Release. 2013;172(3):715–729.
  • Alexander A, Ajazuddin KJ, Saraf S, Saraf S. Formulation and evaluation of chitosan-based long-acting injectable hydrogel for PEGylated melphalan conjugate. J Pharm Pharmacol. 2014;66(9):1240–1250.24824413
  • Alexander A, Ajazuddin PRJ, Saraf S, Saraf S. Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. J Controlled Release. 2016;241:110–124.
  • Maria João Gomes J, Bruno S. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system. Int J Nanomedicine. 2014;9(1):1757–1769.24741312
  • Song H, Wei M, Zhang N, et al. Enhanced permeability of blood–brain barrier and targeting function of brain via borneol-modified chemically solid lipid nanoparticle. Int J Nanomedicine. 2018;13:1869–1879.29636606
  • Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Controlled Release. 2004;100(1):5–28.
  • Alexander A, Ajazuddin M, Swarna M, Sharma M, Tripathi D. Polymers and permeation enhancers: specialized components of mucoadhesives. Stamford J Pharm Sci. 2011;4(1):91–95.
  • Gelperina S, Maksimenko O, Khalansky A, et al. Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide) nanoparticles: influence of the formulation parameters. Eur J Pharm Biopharm. 2010;74(2):157–163.19755158
  • Alexander A, Dwivedi S, Giri TK, et al. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. J Controlled Release. 2012;164(1):26–40.
  • Bruno Fonseca-Santos MPDG, Chorilli M. Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. Int J Nanomedicine. 2015;10(1):4981–5003.26345528
  • Khan AR, Liu M, Khan MW, Zhai G. Progress in brain targeting drug delivery system by nasal route. J Controlled Release. 2017;268:364–389.
  • Ramanathan S, Archunan G, Sivakumar M, et al. Theranostic applications of nanoparticles in neurodegenerative disorders. Int J Nanomedicine. 2018;13:5561–5576.30271147
  • Kuo YC, Chang YH, Rajesh R. Targeted delivery of etoposide, carmustine and doxorubicin to human glioblastoma cells using methoxy poly(ethylene glycol)poly(epsiloncaprolactone) nanoparticles conjugated with wheat germ agglutinin and folic acid. Mater Sci Eng C Mater Biol Appl. 2019;96:114–128.30606517
  • Li H, Tong Y, Bai L, et al. Lactoferrin functionalized PEG-PLGA nanoparticles of shikonin for brain targeting therapy of glioma. Int J Biol Macromol. 2018;107(Pt A):204–211.28863897
  • Fernandes J, Ghate MV, Basu Mallik S, Lewis SA. Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor. Int J Pharm. 2018;547(1–2):563–571.29906562
  • Rukmangathen R, Yallamalli IM, Yalavarthi PR. Biopharmaceutical potential of selegiline loaded chitosan nanoparticles in the management of Parkinson’s disease. Curr Drug Discov Technol. Epub April 18, 2018. doi:10.2174/1570163815666180418144019
  • Yang H. Nanoparticle-mediated brain-specific drug delivery, imaging, and diagnosis. Pharm Res. 2010;27(9):1759–1771.20593303
  • Ku S, Yan F, Wang Y, Sun Y, Yang N, Ye L. The blood-brain barrier penetration and distribution of PEGylated fluorescein-doped magnetic silica nanoparticles in rat brain. Biochem Biophys Res Commun. 2010;394(4):871–876.20206605
  • Teleanu DM, Chircov C, Grumezescu AM, Volceanov A. Blood-brain delivery methods using nanotechnology. Pharmaceutics. 2018;10(4):269.
  • Ren J, Shen S, Wang D, et al. The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials. 2012;33(11):3324–3333.22281423
  • Qiao R, Jia Q, Huwel S, et al. Receptor-mediated delivery of magnetic nanoparticles across the blood-brain barrier. ACS Nano. 2012;6(4):3304–3310.22443607
  • Frigell J, Garcia I, Gomez-Vallejo V, Llop J, Penades S. 68Ga-labeled gold glyconanoparticles for exploring blood-brain barrier permeability: preparation, biodistribution studies, and improved brain uptake via neuropeptide conjugation. J Am Chem Soc. 2014;136(1):449–457.24320878
  • Tomitaka A, Ota S, Nishimoto K, Arami H, Takemura Y, Nair M. Dynamic magnetic characterization and magnetic particle imaging enhancement of magnetic-gold core-shell nanoparticles. Nanoscale. 2019;11:6489–6496.
  • Zhao L, Li Y, Zhu J, et al. Chlorotoxin peptide-functionalized polyethylenimine-entrapped gold nanoparticles for glioma SPECT/CT imaging and radionuclide therapy. J Nanobiotechnology. 2019;17(1):30.30782154
  • Fahmy HM, Fathy MM, Abd-Elbadia RA, Elshemey WM. Targeting of Thymoquinone-loaded mesoporous silica nanoparticles to different brain areas: in vivo study. Life Sci. 2019;222:94–102.30826496
  • Yang Z, Zhang Y, Yang Y, et al. Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine. 2010;6(3):427–441.20056170
  • Li X, Tsibouklis J, Weng T, et al. Nano carriers for drug transport across the blood-brain barrier. J Drug Target. 2017;25(1):17–28.27126681
  • Alexander A, Ajazuddin KJ, Saraf S, Saraf S. Polyethylene glycol (PEG)-Poly(N-isopropylacrylamide) (PNIPAAm) based thermosensitive injectable hydrogels for biomedical applications. Eur J Pharm Biopharm. 2014;88(3):575–585.25092423
  • Li XCY. Study on synthesis and chloramphenicol release of poly (2-hydroxyethylmethacrylate-co-acrylamide) hydrogels. Chin J Chem Eng. 2008;16:640–645.
  • Weng T, Guo J, Li X, et al. Synthesis, chloramphenicol uptake, and in vitro release of poly(AMPS–TEA-Co-AAm) gels with affinity for both water and alcohols. Int J Polym Mater Polym Biomater. 2014;63(2):73–79.
  • Chen W, Zou Y, Zhong Z, Haag R. Cyclo(RGD)-decorated reduction-responsive nanogels mediate targeted chemotherapy of integrin overexpressing human glioblastoma in vivo. Small. 2017;13(6):1–9.
  • Warren G, Makarov E, Lu Y, et al. Amphiphilic cationic nanogels as brain-targeted carriers for activated nucleoside reverse transcriptase inhibitors. J J Neuroimmune Pharmacol. 2015;10(1):88–101.
  • Azadi A, Hamidi M, Khoshayand MR, Amini M, Rouini MR. Preparation and optimization of surface-treated methotrexate-loaded nanogels intended for brain delivery. Carbohydr Polym. 2012;90(1):462–471.24751066
  • Seok GELL. Invention of polysaccharide-based nanoparticles for enhancing drug permeability across the blood brain barrier. NSTI-Nanotech. 2008;2:379–381.
  • Li X, Cui Y. Study on synthesis and chloramphenicol release of poly(2-hydroxyethylmethacrylate-co-acrylamide) Hydrogels. Chin J Chem Eng. 2008;16(4):640–645.
  • Ganta S, Amiji M. Coadministration of Paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm. 2009;6(3):928–939.19278222
  • Ganta S, Deshpande D, Korde A, Amiji M. A review of multifunctional nanoemulsion systems to overcome oral and CNS drug delivery barriers. Mol Membr Biol. 2010;27(7):260–273.20929336
  • Shobo A, Pamreddy A, Kruger HG, et al. Enhanced brain penetration of pretomanid by intranasal administration of an oil-in-water nanoemulsion. Nanomedicine (London, England). 2018;13(9):997–1008. doi:10.2217/nnm-2017-0365
  • Ahmad N, Ahmad R, Naqvi AA, et al. Intranasal delivery of quercetin-loaded mucoadhesive nanoemulsion for treatment of cerebral ischaemia. Artif Cells Nanomed Biotechnol. 2018;46(4):717–729. doi:10.1080/21691401.2017.133702428604104
  • Ahmad N, Ahmad R, Abbas Naqvi A, et al. The effect of safranal loaded mucoadhesive nanoemulsion on oxidative stress markers in cerebral ischemia. Artif Cells Nanomed Biotechnol. 2017;45(4):775–787. doi:10.1080/21691401.2016.122865927609117
  • Abdou EM, Kandil SM, Miniawy H. Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion. Int J Pharm. 2017;529(1–2):667–677. doi:10.1016/j.ijpharm.2017.07.03028729175
  • Dordevic SM, Cekic ND, Savic MM, et al. Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: design, characterization and in vivo pharmacokinetic evaluation. Int J Pharm. 2015;493(1–2):40–54. doi:10.1016/j.ijpharm.2015.07.00726209070
  • Tan SL, Stanslas J, Basri M, et al. Nanoemulsion-based parenteral drug delivery system of carbamazepine: preparation, characterization, stability evaluation and blood-brain pharmacokinetics. Curr Drug Deliv. 2015;12(6):795–804.26324229
  • Bonferoni MC, Rossi S. Nanoemulsions for “Nose-to-Brain” Drug Delivery. Pharmaceutics 2019;11(2):84–101.
  • Yan H, Wang J, Yi P, et al. Imaging brain tumor by dendrimer-based optical/paramagnetic nanoprobe across the blood-brain barrier. Chem Commun (Cambridge, England). 2011;47(28):8130–8132. doi:10.1039/c1cc12007g
  • He H, Li Y, Jia XR, et al. PEGylated Poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials. 2011;32(2):478–487. doi:10.1016/j.biomaterials.2010.09.00220934215
  • Dhanikula RS, Argaw A, Bouchard JF, Hildgen P. Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability. Mol Pharm. 2008;5(1):105–116. doi:10.1021/mp700086j18171013
  • Verma C, Janghel A, Deo S, et al. Comprehensive advancement on nanomedicinesalong with its various biomedical applications. Res J Pharm Technol. 2015;8(7):945. doi:10.5958/0974-360X.2015.00159.6
  • Lu Y, Han S, Zheng H, et al. A novel RGDyC/PEG co-modified PAMAM dendrimer-loaded arsenic trioxide of glioma targeting delivery system. Int J Nanomedicine. 2018;13:5937–5952. doi:10.2147/IJN.S17541830323584
  • Lu Y, Han S, Zheng H, et al. A novel RGDyC/PEG co-modified PAMAM dendrimer-loaded arsenic trioxide of glioma targeting delivery system. Int J Nanomedicine. 2018;13:5937–5952. doi:10.2147/IJN.S17541830323584
  • Gothwal A, Nakhate KT, Alexander A, Ajazuddin GU. Boosted memory and improved brain bioavailability of rivastigmine: targeting effort to the brain using covalently tethered lower generation PAMAM dendrimers with lactoferrin. Mol Pharm. 2018;15(10):4538–4549. doi:10.1021/acs.molpharmaceut.8b0053730156844
  • Li Y, He H, Jia X, Lu WL, Lou J, Wei Y. A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials. 2012;33(15):3899–3908. doi:10.1016/j.biomaterials.2012.02.00422364698
  • Ghaderi S, Ramesh B, Seifalian AM. Fluorescence nanoparticles “quantum dots” as drug delivery system and their toxicity: a review. J Drug Target. 2011;19(7):475–486. doi:10.3109/1061186X.2010.52622720964619
  • Shafq Al-Azzawi DM, Guildford AL, Phillips G, Santin M. Dendrimeric poly(Epsilon-Lysine) delivery systems for the enhanced permeability of flurbiprofen across the blood-brain barrier in Alzheimer’s disease. Int J Mol Sci. 2018;19(10):3224. doi:10.3390/ijms19103224
  • Gao J, Chen K, Xie R, et al. In vivo tumor-targeted fluorescence imaging using near-infrared non-cadmium quantum dots. Bioconjug Chem. 2010;21(4):604–609. doi:10.1021/bc900323v20369817
  • Gao X, Chen J, Chen J, Wu B, Chen H, Jiang X. Quantum dots bearing lectin-functionalized nanoparticles as a platform for in vivo brain imaging. Bioconjug Chem. 2008;19(11):2189–2195. doi:10.1021/bc800269818922029
  • Qiao L, Sun T, Zheng X, Zheng M, Xie Z. Exploring the optimal ratio of d-glucose/l-aspartic acid for targeting carbon dots toward brain tumor cells. Mater Sci Eng C Mater Biol Appl. 2018;85:1–6. doi:10.1016/j.msec.2017.12.01129407137
  • Tang J, Huang N, Zhang X, et al. Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma. Int J Nanomedicine. 2017;12:3899–3911. doi:10.2147/IJN.S13316628579776
  • Yang HY, Fu Y, Jang MS, et al. CdSe@ZnS/ZnS quantum dots loaded in polymeric micelles as a pH-triggerable targeting fluorescence imaging probe for detecting cerebral ischemic area. Colloids Surf B Biointerfaces. 2017;155:497–506. doi:10.1016/j.colsurfb.2017.04.05428475986
  • Agrawal M, Saraf S, Saraf S, et al. Nose-to-brain drug delivery: an update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Controlled Release. 2018;281:139–177. doi:10.1016/j.jconrel.2018.05.011
  • Alam S, Khan ZI, Mustafa G, et al. Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study. Int J Nanomedicine. 2012;7:5705–5718. doi:10.2147/IJN.S3532923180965
  • Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. Mechanism of intranasal drug delivery directly to the brain. Life Sci. 2018;195:44–52. doi:10.1016/j.lfs.2017.12.02529277310
  • Alexander A, Saraf S. Nose-to-brain drug delivery approach: A key to easily accessing the brain for the treatment of Alzheimer’s disease. Neural Regener Res. 2018;13(12):2102. doi:10.4103/1673-5374.233432
  • Nigam K, Kaur A, Tyagi A, et al. Nose-to-brain delivery of lamotrigine-loaded PLGA nanoparticles. Drug Deliv Transl Res. 2019. doi:10.1007/s13346-019-00622-5
  • Musumeci T, Serapide MF, Pellitteri R, et al. Oxcarbazepine free or loaded PLGA nanoparticles as effective intranasal approach to control epileptic seizures in rodents. Eur J Pharm Biopharm. 2018;133:309–320. doi:10.1016/j.ejpb.2018.11.00230399400
  • Chu L, Wang A, Ni L, et al. Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting. Drug Deliv. 2018;25(1):1634–1641.30176744
  • Wong HL, Wu XY, Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev. 2012;64(7):686–700. doi:10.1016/j.addr.2011.10.00722100125
  • Kuo YC, Chou PR. Neuroprotection against degeneration of sk-N-mc cells using neuron growth factor-encapsulated liposomes with surface cereport and transferrin. J Pharm Sci. 2014;103(8):2484–2497. doi:10.1002/jps.2408125041794
  • Su Z, Xing L, Chen Y, et al. Lactoferrin-modified poly(ethylene glycol)-grafted BSA nanoparticles as a dual-targeting carrier for treating brain gliomas. Mol Pharm. 2014;11(6):1823–1834. doi:10.1021/mp500238m24779677
  • Karim R, Palazzo C, Evrard B, Piel G. Nanocarriers for the treatment of glioblastoma multiforme: current state-of-the-art. J Controlled Release. 2016;227:23–37. doi:10.1016/j.jconrel.2016.02.026
  • Nel AE, Madler L, Velegol D, et al. Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater. 2009;8(7):543–557. doi:10.1038/nmat244219525947
  • Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev. 2009;61(6):428–437. doi:10.1016/j.addr.2009.03.00919376175
  • Salvati A, Pitek AS, Monopoli MP, et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat Nanotechnol. 2013;8(2):137–143. doi:10.1038/nnano.2012.23723334168
  • Ponka P, Lok CN. The transferrin receptor: role in health and disease. Int J Biochem Cell Biol. 1999;31(10):1111–1137. doi:10.1016/S1357-2725(99)00070-910582342
  • Xie R, Dong L, Du Y, et al. In vivo metabolic labeling of sialoglycans in the mouse brain by using a liposome-assisted bioorthogonal reporter strategy. Proc Natl Acad Sci U S A. 2016;113(19):5173–5178. doi:10.1073/pnas.151652411327125855