CoChat
Sign Up
Cited by 25Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsBarrier Structure and Function Studies

Increased brain uptake of pterostilbene loaded folate modified micellar delivery system

Open access
Wang, Yinan, Su, Yanan, Yang, Yunqiao, Jin, Huan, Wu, Moli, Wang, Qian, Sun, Pengyuan, Zhang, Jianbin +2 more·2022·Drug Delivery
DOI 10.1080/10717544.2022.2126559PMC PMC9848421
Open this paper in CoChat — free account

Abstract

Effective chemotherapy for clinical treatment of brain diseases is still lacking due to the poor penetration of the blood-brain barrier (BBB). The aim of this study was to construct a folate modified pterostilbene (Pt) loaded polymeric micellar delivery system (F-Pt/M) with mPEG-PCL as carrier material to aim at penetrating the BBB for brain tissue targeting via receptor-mediated endocytosis. In this study, F-Pt/M was prepared using thin-film hydration method and then optimized by response surface methodology (RSM) with the entrapment efficiency (EE), drug loading (DL) and hydrodynamic diameter (HD) as indexes. The average hydrodynamic diameter and zeta potential of optimal F-Pt/M were 133.2 nm and 24.6 mV, respectively. DL (18.3%) and EE (98.6%) made the solubility of Pt in water about 25 times higher than that of crude Pt. Results of DSC evaluation revealed that drugs were successfully encapsulated inside the polymeric micelles. TEM images showed that homogeneous spherical micellar structures with a narrow size distribution were developed. The release result in vitro showed that F-Pt/M presented sustained release behavior compared to control free Pt solution. Compared to non-targeted Pt/M, F-Pt/M had a significantly higher cytotoxicity against FR-overexpressing A172 cells. In vitro cellular uptake tests illustrated that the micellar delivery system could significantly improve the accumulation of drugs in target cells via receptor-mediated endocytosis. BBB penetration value (P) of F-Pt/M was about 4 folds higher than that of free Pt group. In addition, drug targeting index (DTI) was calculated to determine targeting of F-Pt/M to the brain which was found to be 4.89, implying improved brain targeting was achieved. Hence, the developed F-Pt/M exhibited great potential for delivering more drug molecules across the BBB for the treatment of brain diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1080/10717544.2022.2126559

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • FA-Pt/mPEG-PCL shows enhanced toxicity toward folate receptor-overexpressing A172 cells compared to free Pt/mPEG-PCL.

    “Compared to free Pt/mPEG-PCL, FA-Pt/mPEG-PCL showed enhanced toxicity toward folate receptors-overexpressing A172 cells”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [187]

  • Folate participates in condensation of Pt in A172 cells through folate receptor-mediated route.

    “which proves folate anticipated in the condensation of Pt in A172 cells through folate receptor-mediated route.”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [187]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 71

  1. Amarnath Satheesh M, Pari L. (2006). The antioxidant role of pterostilbene in streptozotocin-nicotinamide-induced type 2 diabetes mellitus in Wistar rats. J Pharm Pharmacol 58: 1483– 90. 17132211
  2. Betzer O, Shilo M, Opochinsky R, et al. (2017). The effect of nanoparticle size on the ability to cross the blood-brain barrier: an in vivo study. Nanomedicine (Lond) 12: 1533– 46. 28621578
  3. Bhakkiyalakshmi E, Shalini D, Sekar TV, et al. (2014). Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through Nrf2. Br J Pharmacol 171: 1747– 57. 24417315 PMC3966753
  4. Chang J, Rimando A, Pallas M, et al. (2012). Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease. Neurobiol Aging 33: 2062– 71. 21982274
  5. Dong Y, Feng SS. (2007). In vitro and in vivo evaluation of methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles for small-molecule drug chemotherapy. Biomaterials 28: 4154– 60. 17576004
  6. Duan Y, Wang J, Yang X, et al. (2015). Curcumin-loaded mixed micelles: preparation, optimization, physicochemical properties and cytotoxicity in vitro. Drug Deliv 22: 50– 7. 24417664
  7. Fernandez M, Javaid F, Chudasama V. (2018). Advances in targeting the folate receptor in the treatment/imaging of cancers. Chem Sci 9: 790– 810. 29675145 PMC5890329
  8. Ferrer P, Asensi M, Segarra R, et al. (2005). Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma. Neoplasia 7: 37– 47. 15736313 PMC1490314
  9. Gao H. (2017). Perspectives on dual targeting delivery systems for brain tumors. J Neuroimmune Pharmacol 12: 6– 16. 27270720
  10. Gothwal A, Khan I, Gupta U. (2016). Polymeric micelles: recent advancements in the delivery of anticancer drugs. Pharm Res 33: 18– 39. 26381278
  11. Gul M, Shah FA, Sahar NU, et al. (2022). Formulation optimization, in vitro and in vivo evaluation of agomelatine-loaded nanostructured lipid carriers for augmented antidepressant effects. Colloids Surf B Biointerfaces 216: 112537. 35561634
  12. Guo Y, Gao T, Fang F, et al. (2021). A novel polymer micelle as a targeted drug delivery system for 10-hydroxycamptothecin with high drug-loading properties and anti-tumor efficacy. Biophys Chem 279: 106679. 34547633
  13. Han L, Jiang C. (2021). Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies. Acta Pharm Sin B 11: 2306– 25. 34522589 PMC8424230
  14. He X, Wang X, Yang L, et al. (2022). Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer’s disease treatment by anti-neuroinflammation and neuroprotection. Acta Pharm Sin B 12: 1987– 99. 35847512 PMC9279705
  15. Jain A, Jain SK. (2015). Ligand-appended BBB-targeted nanocarriers (LABTNs). Crit Rev Ther Drug Carrier Syst 32: 149– 80. 25955883
  16. Juyang Z, Wolf B. (2021). Impact of type of sugar beet pectin-sodium caseinate interaction on emulsion properties at pH 4.5 and pH 7. Foods 10: 631. 33802694 PMC8002390
  17. Kalhapure RS, Suleman N, Mocktar C, et al. (2015). Nanoengineered drug delivery systems for enhancing antibiotic therapy. J Pharm Sci 104: 872– 905. 25546108
  18. Katekar R, Thombre G, Riyazuddin M, et al. (2020). Pharmacokinetics and brain targeting of trans-resveratrol loaded mixed micelles in rats following intravenous administration. Pharm Dev Technol 25: 300– 7. 31609159
  19. Khan A, Aqil M, Imam SS, et al. (2018). Temozolomide loaded nano lipid based chitosan hydrogel for nose to brain delivery: characterization, nasal absorption, histopathology and cell line study. Int J Biol Macromol 116: 1260– 7. 29775717
  20. Khan A, Imam SS, Aqil M, et al. (2016). Brain targeting of temozolomide via the intranasal route using lipid-based nanoparticles: brain pharmacokinetic and scintigraphic analyses. Mol Pharm 13: 3773– 82. 27661966
  21. Khan N, Shah FA, Rana I, et al. (2020). Nanostructured lipid carriers-mediated brain delivery of carbamazepine for improved in vivo anticonvulsant and anxiolytic activity. Int J Pharm 577: 119033. 31954864
  22. Kheiri Manjili H, Ghasemi P, Malvandi H, et al. (2017a). Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles. Eur J Pharm Biopharm 116: 17– 30. 27756682
  23. Kheiri Manjili H, Sharafi A, Attari E, Danafar H. (2017b). Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL-PEG-PCL copolymeric-based micelles. Artif Cells Nanomed Biotechnol 45: 1728– 39. 28147711
  24. Kucheryavykh YV, Davila J, Ortiz-Rivera J, et al. (2019). Targeted delivery of nanoparticulate cytochrome C into glioma cells through the proton-coupled folate transporter. Biomolecules 9: 154. 31003476 PMC6523331
  25. Kuo YC, Chang YH, Rajesh R. (2019). 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 96: 114– 28. 30606517
  26. Lei T, Yang Z, Xia X, et al. (2021). A nanocleaner specifically penetrates the bloodbrain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer’s disease. Acta Pharm Sin B 11: 4032– 44. 35024324 PMC8727781
  27. Lingineni K, Belekar V, Tangadpalliwar SR, Garg P. (2017). The role of multidrug resistance protein (MRP-1) as an active efflux transporter on blood-brain barrier (BBB) permeability. Mol Divers 21: 355– 65. 28050687
  28. Liu J, Chen F, Tian W, et al. (2014). Optimization and characterization of curcumin loaded in octenylsuccinate oat beta-glucan micelles with an emphasis on degree of substitution and molecular weight. J Agric Food Chem 62: 7532– 40. 25005779
  29. Liu J, Fan C, Yu L, et al. (2016). Pterostilbene exerts an anti-inflammatory effect via regulating endoplasmic reticulum stress in endothelial cells. Cytokine 77: 88– 97. 26551859
  30. Liu Q, Chen J, Qin Y, et al. (2019). Encapsulation of pterostilbene in nanoemulsions: influence of lipid composition on physical stability, in vitro digestion, bioaccessibility, and Caco-2 cell monolayer permeability. Food Funct 10: 6604– 14. 31552977
  31. Liu Y, Li K, Pan J, et al. (2010). Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of Docetaxel. Biomaterials 31: 330– 8. 19783040
  32. Liu Y, You Y, Lu J, et al. (2020). Recent advances in synthesis, bioactivity, and pharmacokinetics of pterostilbene, an important analog of resveratrol. Molecules 25: 5166. 33171952 PMC7664215
  33. Lu L, Shen X, Tao B, et al. (2019). The nanoparticle-facilitated autophagy inhibition of cancer stem cells for improved chemotherapeutic effects on glioblastomas. J Mater Chem B 7: 2054– 62. 32254809
  34. Luiz MT, Delello Di Filippo L, Tofani LB, et al. (2021). Highlights in targeted nanoparticles as a delivery strategy for glioma treatment. Int J Pharm 604: 120758. 34090991
  35. Luo D, Wang X, Zhong X, et al. (2022). MPEG-PCL nanomicelles platform for synergistic metformin and chrysin delivery to breast cancer in mice. ACAMC 22: 280– 93. 34165412
  36. Ma Z, Zhang X, Xu L, et al. (2019). Pterostilbene: mechanisms of its action as oncostatic agent in cell models and in vivo studies. Pharmacol Res 145: 104265. 31078746
  37. Matsumoto Y, Miyamoto Y, Cabral H, et al. (2016). Enhanced efficacy against cervical carcinomas through polymeric micelles physically incorporating the proteasome inhibitor MG132. Cancer Sci 107: 773– 81. 26987571 PMC4968607
  38. McCord E, Pawar S, Koneru T, et al. (2021). Folate receptors’ expression in gliomas may possess potential nanoparticle-based drug delivery opportunities. ACS Omega 6: 4111– 8. 33623837 PMC7893640
  39. Mei D, Chen B, He B, et al. (2019). Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer. Acta Pharm Sin B 9: 1061– 77. 31649854 PMC6804482
  40. Nakanishi T, Fukushima S, Okamoto K, et al. (2001). Development of the polymer micelle carrier system for doxorubicin. J Control Release 74: 295– 302. 11489509
  41. Nour SA, Abdelmalak NS, Naguib MJ, et al. (2016). Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies. Drug Deliv 23: 3681– 95. 27648847
  42. Pardridge WM. (2003). Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv 3: 90– 105, 51. 14993430
  43. Pardridge WM. (2007). Drug targeting to the brain. Pharm Res 24: 1733– 44. 17554607
  44. Rana I, Khan N, Ansari MM, et al. (2020). Solid lipid nanoparticles-mediated enhanced antidepressant activity of duloxetine in lipopolysaccharide-induced depressive model. Colloids Surf B Biointerfaces 194: 111209. 32599505
  45. Raval N, Maheshwari R, Shukla H, et al. (2021). Multifunctional polymeric micellar nanomedicine in the diagnosis and treatment of cancer. Mater Sci Eng C Mater Biol Appl 126: 112186. 34082985
  46. Riche DM, McEwen CL, Riche KD, et al. (2013). Analysis of safety from a human clinical trial with pterostilbene. J Toxicol 2013: 463595. 23431291 PMC3575612
  47. Richter A, Olbrich C, Krause M, et al. (2010). Polymeric micelles for parenteral delivery of sagopilone: physicochemical characterization, novel formulation approaches and their toxicity assessment in vitro as well as in vivo. Eur J Pharm Biopharm 75: 80– 9. 20188169
  48. Romio M, Morgese G, Trachsel L, et al. (2018). Poly(2-oxazoline)-pterostilbene block copolymer nanoparticles for dual-anticancer drug delivery. Biomacromolecules 19: 103– 11. 29216713
  49. Ruan S, Zhou Y, Jiang X, Gao H. (2021). Rethinking CRITID procedure of brain targeting drug delivery: circulation, blood brain barrier recognition, intracellular transport, diseased cell targeting, internalization, and drug release. Adv Sci (Weinh) 8: 2004025. 33977060 PMC8097396
  50. Rubab S, Naeem K, Rana I, et al. (2021). Enhanced neuroprotective and antidepressant activity of curcumin-loaded nanostructured lipid carriers in lipopolysaccharide-induced depression and anxiety rat model. Int J Pharm 603: 120670. 33964337
  51. Ruiz MJ, Fernandez M, Pico Y, et al. (2009). Dietary administration of high doses of pterostilbene and quercetin to mice is not toxic. J Agric Food Chem 57: 3180– 6. 19292443
  52. Shahid A, Bhatt P, Miller A, Sutariya V. (2021). Honokiol-loaded methoxy poly (ethylene glycol) polycaprolactone micelles for the treatment of age-related macular degeneration. Assay Drug Dev Technol 19: 350– 60. 34227879
  53. Silva F, Figueiras A, Gallardo E, et al. (2014). Strategies to improve the solubility and stability of stilbene antioxidants: a comparative study between cyclodextrins and bile acids. Food Chem 145: 115– 25. 24128457
  54. Song K, Xin M, Zhang F, et al. (2020). Novel ultrasmall nanomicelles based on rebaudioside A: A potential nanoplatform for the ocular delivery of pterostilbene. Int J Pharm 577: 119035. 31953080
  55. Valenzuela-Oses JK, Garcia MC, Feitosa VA, et al. (2017). Development and characterization of miltefosine-loaded polymeric micelles for cancer treatment. Mater Sci Eng C Mater Biol Appl 81: 327– 33. 28887980
  56. Wang F, Chen Y, Zhang D, et al. (2012). Folate-mediated targeted and intracellular delivery of paclitaxel using a novel deoxycholic acid-O-carboxymethylated chitosan-folic acid micelles. Int J Nanomedicine 7: 325– 37. 22287842 PMC3266000
  57. Wei W, Li S, Xu H, et al. (2018). MPEG-PCL copolymeric micelles for encapsulation of azithromycin. AAPS PharmSciTech 19: 2041– 7. 29675667
  58. Wei W, Zhang Y, Li R, et al. (2022). Oral delivery of pterostilbene by L-arginine-mediated “nano-bomb” carrier for the treatment of ulcerative colitis. Int J Nanomedicine 17: 603– 16. 35177902 PMC8843770
  59. Wei X, Gong C, Gou M, et al. (2009). Biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol) copolymers as drug delivery system. Int J Pharm 381: 1– 18. 19664700
  60. Weitman SD, Lark RH, Coney LR, et al. (1992). Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer Res 52: 3396– 401. 1596899
  61. Xie Z, Guan H, Chen X, et al. (2007). A novel polymer-paclitaxel conjugate based on amphiphilic triblock copolymer. J Control Release 117: 210– 6. 17188776
  62. Yang CN, Peng WY, Lin LC, Tsai TH. (2021). Protein unbound pharmacokinetics of ambroxol in the blood and brains of rats and the interaction of ambroxol with Polygala tenuifolia by multiple microdialysis. J Ethnopharmacol 269: 113764. 33383115
  63. Yang XB, Wang XB, Pan WS, et al. (2011). Optimization and characterization of dry powder of fanhuncaoin for inhalation based on selection of excipients. Chem Pharm Bull (Tokyo) 59: 929– 37. 21804235
  64. Yang Y, Yun K, Li Y, et al. (2021). Self-assembled multifunctional polymeric micelles for tumor-specific bioimaging and synergistic chemo-phototherapy of cancer. Int J Pharm 602: 120651. 33915181
  65. Yao H, Zhao J, Wang Z, et al. (2020). Enhanced anticancer efficacy of cantharidin by mPEG-PLGA micellar encapsulation: an effective strategy for application of a poisonous traditional Chinese medicine. Colloids Surf B Biointerfaces 196: 111285. 32771818
  66. Zhao L, Du J, Duan Y, et al. (2012a). Curcumin loaded mixed micelles composed of Pluronic P123 and F68: preparation, optimization and in vitro characterization. Colloids Surf B Biointerfaces 97: 101– 8. 22609589
  67. Zhao P, Wang H, Yu M, et al. (2012b). Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation. Eur J Pharm Biopharm 81: 248– 56. 22446630
  68. Zhao X, Shi A, Ma Q, et al. (2021). Nanoparticles prepared from pterostilbene reduce blood glucose and improve diabetes complications. J Nanobiotechnology 19: 191. 34176494 PMC8237509
  69. Zheng N, Dai W, Zhang H, et al. (2015). Lanreotide-conjugated PEG-DSPE micelles: an efficient nanocarrier targeting to somatostatin receptor positive tumors. J Drug Target 23: 67– 78. 25366085
  70. Zou Y, Wang X, Bi D, et al. (2021). Pterostilbene nanoparticles with small particle size show excellent anti-breast cancer activity in vitro and in vivo. Nanotechnology 32: 325102. 33946061
  71. Zuo J, Gao Y, Bou-Chacra N, Löbenberg R. (2014). Evaluation of the DDSolver software applications. Biomed Res Int 2014: 204925. 24877067 PMC4022259

Cited by

Sorted by citations

Authors
Wang, Y., Su, Y., Yang, Y., Jin, H., Wu, M., Wang, Q., Sun, P., Zhang, J., Yang, X., & Shu, X.
Affiliations
  • Dalian Medical University (CN)
  • College of Basic Medical Sciences, Dalian Medical University
Corresponding author
  • Yang, Xiaobo
  • Shu, Xiaohong
ORCID
Venue
Drug Delivery
Publisher
Informa UK Limited
Published
2022-09-21
Volume
29
Issue
1
Pages
3071-3086
ISSN
  • 1071-7544 (ISSN-L)
  • 1521-0464
DOI
10.1080/10717544.2022.2126559
PMC
PMC9848421
OpenAlex
W4296625306
Cited by
25
References
2
Citations by year
2026: 9 · 2025: 7 · 2024: 4 · 2023: 5
FWCI
1.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Drug Delivery (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81672945, 81502992)
  • Science Project of Liaoning Provincial Education Department (LJKZ0827)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
pterostilbene, folic acid, polymeric micelles, mPEG-PCL, blood-brain barrier penetration, brain targeting, receptor-mediated endocytosis, A172 cells, drug loading, sustained drug release, brain disorders
MeSH terms
Brain, Brain Diseases, Delayed-Action Preparations, Drug Carriers, Folic Acid, Humans, Micelles, Polyethylene Glycols, Polymers, Stilbenes, Water, Drug Delivery Systems

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review