Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Synthesis and in Vitro Evaluation of Self-Assembling Biocompatible Heparin-Based Targeting Polymeric Micelles for Delivery of Doxorubicin to Leukemic Cells Publisher



Emami J1 ; Kazemi M2, 3 ; Mirian M4
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Nanotechnology Research Center, Medical Basic Research Sciences Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  3. 3. Department of Pharmaceutics, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  4. 4. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Research in Pharmaceutical Sciences Published:2025


Abstract

Background and purpose: Biodegradable polymeric micelles have emerged as one of the most promising platforms for targeted drug delivery. In the present study, a polymeric micelle composed of folic acid (FA), heparin (HEP), dexamethasone (DEX), and (FA-PEG-HEP-CA-TOC) was developed for the delivery of doxorubicin (DOX) to leukemic cells. Experimental approach: FA-HEP-DEX was synthesized and characterized by 1H-NMR. DOX-loaded micelles were prepared using a dialysis method. The impact of various processing variables, including polymer-to-drug ratio, dialysis temperature, and solvent type, on the physicochemical properties of the micelles were evaluated. In vitro, cellular uptake and cytotoxicity of the micelles in folate receptor-positive (K562) and negative (HepG2) cells were evaluated. Findings/Results: The 1H-NMR results confirmed the successful synthesis of FA-HEP-DEX. DOX-loaded micelles exhibited an average particle size of 117 to 181 nm with a high drug entrapment efficiency (36% to 71%). DOX-loaded micelles also showed sustained drug-release behavior. DOX-loaded FA-HEP-DEX micelles exhibited higher cellular uptake and in vitro cytotoxicity than free DOX and DOX-loaded HEP-DEX micelles in K562 cells. Conclusions and implications: DOX was well incorporated into the micelles with high entrapment efficiency due to high solubility of DOX in DEX as the hydrophobic component of the micelle structure. The higher cellular uptake and cell toxicity of targeted micelles correspond to the presence of FA on the micelle surface, which promotes cell internalization of the micelles via specific receptor-mediated endocytosis. Our results indicated the potential of DOX-loaded heparin-based micelles with desirable antitumor activity as a targeted drug delivery system in cancer therapy. © 2025 Wolters Kluwer Medknow Publications. All rights reserved.
Related Docs
View other Related Docs
1. Pegylated Multifunctional Ph-Responsive Targeted Polymeric Micelles for Ovarian Cancer Therapy: Synthesis, Characterization and Pharmacokinetic Study, International Journal of Polymeric Materials and Polymeric Biomaterials (2021)
2. In Vitro and in Vivo Evaluation of Novel Dtx-Loaded Multifunctional Heparin-Based Polymeric Micelles Targeting Folate Receptors and Endosomes, Recent Patents on Anti-Cancer Drug Discovery (2020)
3. Novel Ph-Triggered Biocompatible Polymeric Micelles Based on Heparin–Α-Tocopherol Conjugate for Intracellular Delivery of Docetaxel in Breast Cancer, Pharmaceutical Development and Technology (2020)
4. Synthesis and Characterization of Folate-Targeted Dextran/Retinoic Acid Micelles for Doxorubicin Delivery in Acute Leukemia, BioMed Research International (2014)
5. Folated Synperonic-Cholesteryl Hemisuccinate Polymeric Micelles for the Targeted Delivery of Docetaxel in Melanoma, BioMed Research International (2015)
6. Optimisation of Processing Variables Effective on Self-Assembly of Folate Targeted Synpronic-Based Micelles for Docetaxel Delivery in Melanoma Cells, IET Nanobiotechnology (2015)
7. Synthesis and in Vitro/In Vivo Characterization of Raloxifene Grafted Poly(Styrene Maleic Acid)-Poly(Amide-Ether-Ester-Imide) Micelles for Targeted Delivery of Docetaxel in G Protein-Coupled Estrogen Receptor Breast Cancer, Anti-Cancer Agents in Medicinal Chemistry (2018)
8. Folic Acid Targeted Polymeric Micelles Based on Tocopherol Succinate-Pulluan As an Effective Carrier for Epirubicin: Preparation, Characterization and In-Vitro Cytotoxicity Assessment, Current Drug Delivery (2018)
Experts (# of related papers)
View all Related Experts
Jaleh Varshosaz (60)
Farshid Hassanzadeh (40)
Other Related Docs
9. Screening the Most Effective Variables on Physical Properties of Folate-Targeted Dextran/Retinoic Acid Micelles by Taguchi Design, Journal of Nanomaterials (2012)
10. Synthesis of Pluronic® F127-Poly (Methyl Vinyl Ether-Alt-Maleic Acid) Copolymer and Production of Its Micelles for Doxorubicin Delivery in Breast Cancer, Chemical Engineering Journal (2014)
11. Development and in Vitro/In Vivo Evaluation of a Novel Targeted Polymeric Micelle for Delivery of Paclitaxel, International Journal of Biological Macromolecules (2015)
12. Novel Worm-Like Amphiphilic Micelles of Folate-Targeted Cyclodextrin/Retinoic Acid for Delivery of Doxorubicin in Kg-1 Cells, Colloid and Polymer Science (2014)
13. Uptake of Etoposide in Ct-26 Cells of Colorectal Cancer Using Folate Targeted Dextran Stearate Polymeric Micelles, BioMed Research International (2014)
14. Self-Assembly Micelles With Lipid Core of Cholesterol for Docetaxel Delivery to B16f10 Melanoma and Hepg2 Cells, Journal of Liposome Research (2015)
15. Cytotoxic Effect of Pluronic F127-Poly (Methyl Vinyl Ether-Alt-Maleic Acid) Micelles Loaded With Doxorubicin on Mcf-7 Cells, Journal of Isfahan Medical School (2013)
16. Cytotoxic Effects of Targeted Galactosylated Pluronic F127/Pluronicl122 Nano-Sized Micelles Loaded With Doxorubicin in Human Hepatocellular Carcinoma Cell Line, Journal of Isfahan Medical School (2013)
17. Synthesis of Biotin-Targeted Chitosan/Poly (Methyl Vinyl Ether- Alt -Maleic Acid) Copolymeric Micelles for Delivery of Doxorubicin, IET Nanobiotechnology (2017)
18. Biotin-Encoded Pullulan-Retinoic Acid Engineered Nanomicelles: Preparation, Optimization and in Vitro Cytotoxicity Assessment in Mcf-7 Cells, Indian Journal of Pharmaceutical Sciences (2016)
19. Development and in Vitro/In Vivo Evaluation of Hpmc/Chitosan Gel Containing Simvastatin Loaded Self-Assembled Nanomicelles As a Potent Wound Healing Agent, Drug Development and Industrial Pharmacy (2018)
20. Fabrication of Poly Hydroxybutyrate-Polyethylene Glycol-Folic Acid Nanoparticles Loaded by Paclitaxel, Current Drug Delivery (2016)
21. Polyacrylamide-Punicic Acid Conjugate-Based Micelles for Flutamide Delivery in Pc3 Cells of Prostate Cancer: Synthesis, Characterisation and Cytotoxicity Studies, IET Nanobiotechnology (2020)
22. In Vivo Pharmacokinetics, Biodistribution and Anti-Tumor Effect of Paclitaxel-Loaded Targeted Chitosan-Based Polymeric Micelle, Drug Delivery (2016)
23. Synthesis of Pectin-Deoxycholic Acid Conjugate for Targeted Delivery of Anticancer Drugs in Hepatocellular Carcinoma, International Journal of Biological Macromolecules (2019)
24. Preparation and Characterization of Spray-Dried Inhalable Powders Containing Polymeric Micelles for Pulmonary Delivery of Paclitaxel in Lung Cancer, Journal of Pharmacy and Pharmaceutical Sciences (2018)
25. Synthesis, in Vitro Characterization, and Anti-Tumor Effects of Novel Polystyrene-Poly(Amide-Ether-Ester-Imide) Co-Polymeric Micelles for Delivery of Docetaxel in Breast Cancer in Balb/C Mice, Drug Development and Industrial Pharmacy (2018)
26. Folate-Targeted Polyacrylamide/Punicic Acid Nanomicelles for Flutamide Delivery in Prostate Cancer: Characterization, in Vitro Biological Evaluation, and Its Dft Study, Recent Patents on Nanotechnology (2020)
27. Effect of Molecular Weight and Molar Ratio of Dextran on Self-Assembly of Dextran Stearate Polymeric Micelles As Nanocarriers for Etoposide, Journal of Nanomaterials (2012)
28. A Novel Mixed Polymeric Micelle for Co-Delivery of Paclitaxel and Retinoic Acid and Overcoming Multidrug Resistance: Synthesis, Characterization, Cytotoxicity, and Pharmacokinetic Evaluation, Drug Development and Industrial Pharmacy (2018)
29. Folate Targeted Solid Lipid Nanoparticles of Simvastatin for Enhanced Cytotoxic Effects of Doxorubicin in Chronic Myeloid Leukemia, Current Nanoscience (2012)
30. Use of Magnetic Folate-Dextran-Retinoic Acid Micelles for Dual Targeting of Doxorubicin in Breast Cancer, BioMed Research International (2013)
31. Targeted Nanostructured Lipid Carriers for Delivery of Paclitaxel to Cancer Cells: Preparation, Characterization, and Cell Toxicity, Current Drug Delivery (2017)
32. Sirna Delivery Improvement by Co-Formulation of Different Modified Polymers in Erythroleukemic Cell Line K562, Iranian Journal of Basic Medical Sciences (2013)
33. Development and Optimization of Transferrin-Conjugated Nanostructured Lipid Carriers for Brain Delivery of Paclitaxel Using Box–Behnken Design, Pharmaceutical Development and Technology (2017)
34. Magnetic Polyvinyl Caprolactam–Polyvinyl Acetate–Polyethylene Glycol Micelles for Docetaxel Delivery in Breast Cancer: An in Vitro Study on Two Cell Lines of Breast Cancer, Pharmaceutical Development and Technology (2017)
35. An Injectable Thermosensitive Hydrogel/Nanomicelles Composite for Local Chemo-Immunotherapy in Mouse Model of Melanoma, Journal of Biomaterials Applications (2022)
36. Pharmacokinetics, Organ Toxicity and Antitumor Activity of Docetaxel Loaded in Folate Targeted Cholesterol Based Micelles, Current Drug Delivery (2016)
37. Evaluation of Lipid Nanocarriers in the Form of Sln and Their Application in Drug Delivery, Nanochemistry Research (2023)
38. Preparation and Characterization of Micelles of Oligomeric Chitosan Linked to All-Trans Retinoic Acid, Carbohydrate Polymers (2012)
39. Peptide-Based Pegylated Polyurethane Nanoparticles for Paclitaxel Delivery in Hela Cancer Cells: The Art of the Architecture Design in Nanocarriers, Polymer Bulletin (2023)
40. How Do Various Encapsulation Techniques Improve the Oral Delivery of Food Protein Hydrolysates?, Food Frontiers (2025)
41. Effects of Thermal Processing and Ph on the Physicochemical Properties, Stability, and Structure of Taxifolin-Loaded Nanostructured Lipid Carriers, Applied Food Research (2024)
42. Tissue Distribution and Systemic Toxicity Evaluation of Raloxifene Targeted Polymeric Micelles of Poly (Styrene-Maleic Acid)-Poly (Amide- Ether-Ester-Imide)-Poly (Ethylene Glycol) Loaded With Docetaxel in Breast Cancer Bearing Mice, Recent Patents on Anti-Cancer Drug Discovery (2019)
43. Fluorescence Resonance Energy Transfer Monitoring of Ph-Responsive Doxorubicin Release From Carbon Dots/Aptamer Functionalized Magnetic Mesoporous Silica, Nanomedicine (2021)
44. The Effect of Folic Acid-Targeted Nanocarriers in Ultrasound Imaging-Guided Sonodynamic Therapy of Human Cervical Carcinoma (Hela): In Vitro Study, Koomesh (2023)
45. Co-Delivery of Carboplatin and Doxorubicin Using Zif-8 Coated Chitosan-Poly(N-Isopropyl Acrylamide) Nanoparticles Through a Dual Ph/Thermo Responsive Strategy to Breast Cancer Cells, International Journal of Biological Macromolecules (2024)
46. Co-Delivery of Paclitaxel and Α-Tocopherol Succinate by Novel Chitosan-Based Polymeric Micelles for Improving Micellar Stability and Efficacious Combination Therapy, Drug Development and Industrial Pharmacy (2015)
47. Luteinizing Hormone-Releasing Hormone Targeted Poly(Methyl Vinyl Ether Maleic Acid) Nanoparticles for Doxorubicin Delivery to Mcf-7 Breast Cancer Cells, IET Nanobiotechnology (2016)
48. Developing an Accurate Empirical Correlation for Predicting Anti-Cancer Drugs’ Dissolution in Supercritical Carbon Dioxide, Scientific Reports (2022)
49. Lipid Nanocapsules for Imatinib Delivery: Design, Optimization and Evaluation of Anticancer Activity Against Melanoma Cell Line, Iranian Journal of Pharmaceutical Research (2019)
50. Enhanced Solubility, Oral Bioavailability and Anti-Osteoporotic Effects of Raloxifene Hcl in Ovariectomized Rats by Igepal Co-890 Nanomicelles, Pharmaceutical Development and Technology (2019)