Open Access Peer-reviewed Research Article

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Bailey Krueger
Taylor Frazier
Sheila Galbreath
Tarun Goswami corresponding author


The drug release rates of poorly soluble medications such as doxorubicin has been investigated in this paper. Since the drug was fixed, different carriers used to deliver it and their release rates compiled from literature were evaluated in this paper. Even though targeting of drugs is very important in drug delivery, it is not within the scope of this paper. However, functionalization of the carrier may provide this benefit, those constructs are included for comparison in terms of hybrid constructs. Dendrimer, micelles and hybrid constructs used in the delivery of doxorubicin compared in this paper with respect to carrier size and drug loading. Assuming that the dissolution follows a slow release, 40-50% of the drug in the phase I representing a sudden or the burst release, followed by a steady release of 50-60% of the drug in phase II, not all the carriers and their sizes exhibited this behavior. Carriers and hybrid constructs 38nm size were more effective where phases I and II observed, however, as the size decreased to 34 nm or increased above 40nm, minimal release occurred meaning the carriers were too big to penetrate the vasculature permeability. Nano-carriers, dendrimers, micelle, hybrid dendrimers and micelles were found to be effective with the carrier manufacturing, generation, polymer, molecular weight of the carrier and other parameters. The release rate of doxorubicin was found to be effective with dendrimers together with hybrid dendrimer exhibiting a bilinear behavior. Micelles 20nm were more effective representing 60% of release in 10 hours followed by additional 25% in 35 hours exhibiting a bilinear behavior. Size greater than 20nm resulted in slow release reaching less than 10 to 40% of drug. Several drugs exhibited multiple slopes in their kinetics when micelle was used. The therapeutic efficacy of hybrid micelle was superior to other nano-carriers.

nano-carriers, dendrimers, micelle, dissolution kinetics, therapeutic efficacy

Article Details

How to Cite
Krueger, B., Frazier, T., Galbreath, S., & Goswami, T. (2022). Therapeutic efficacies of nano carriers in delivering drugs. Journal of Pharmaceutical and Biopharmaceutical Research, 4(2), 296-317.


  1. Crossen SL and Goswami T. Nanoparticulate carries for drug delivery. Journal of Pharmaceutical and Biopharmaceutical Research, 2022, 4(1): 237-247.
  2. Tomalia DA and Fréchet JMJ. Discovery of dendrimers and dendritic polymers: A brief historical perspective. 2002, 40(16): 2719-2728.
  3. Vogtle F, Richardt G and Werner N. Dendrimer Chemistry: Concepts, Syntheses, Properties, Applications. 2009.
  4. Tomalia D, Christensen J and Boas U. Dendrimers, Dendrons, and Dendritic Polymers: Discovery, Applications, and the Future, Cambridge: Cambridge University Press, 2012.
  5. Abbasi E, Aval SF, Akbarzadeh A, et al. Dendrimers: synthesis, applications, and properties. Nanoscale Research Letters, 9(1): 247.
  6. Hawker C, Frechet J and Philippides A. Dendritic molecules and method of production. Patent 5041516, 20 August 1991.
  7. Huhn S. A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of OP-101 After Intravenous Administration inHealthy Volunteers. 17 September 2018.
  8. Christensen JB. Delivery of Drugs Volume 2: Expectations and Realities of Multifunctional Drug Delivery Systems. 2020, 29-52.
  9. Chauhan A, Patil C, Jain P, et al. 14 - Dendrimer-based marketed formulations and miscellaneous applications in cosmetics, veterinary, and agriculture. In Micro and Nano Technologies, Pharmaceutical Applications of Dendrimers, Elsevier, 2020, 325-334.
  10. Nageli k and Schwender S. The Microscope in Theory and Practice, Palala Press, 2016.
  11. Fox P and Brodkorb A. The casein micelle: Historical aspects, current concepts and significance. International Dairy Journal, 2008, 18(7): 677-684.
  12. Strick JE. Sparks of life: Darwinism and the victorian debates over spontaneous generation, Harvard University Press, 2002.
  13. McBain JW and Gonick E. Cryoscopic Evidence for Micellar Association in Aqueous Solutions of Non-ionic Detergents.
  14. Zhang Y, Huang Y and Li S. Polymeric micelles: nanocarriers for cancer-targeted drug delivery. AAPS PharmSciTech, 2014, 15(4): 862-871.
  15. Kyung Cho E. A Phase II Trial of Genexol-PM and Gemcitabine in Patients With Advanced Non-small-cell Lung Cancer, 18 January 2013.
  16. Nippon Kayaku Co., Ltd. A Phase III Study of NK105 in Patients With Breast Cancer, 19 July 2019.
  17. Nippon Kayaku Co., Ltd. A Study of NK012 in Patients With Advanced, Metastatic Triple Negative BreastCancer, 4 August 2009.
  18. Nippon Kayaku Co., Ltd. Combination Therapy With NC-6004 and Gemcitabine in Advanced Solid Tumors orNon-Small Cell Lung, Biliary and Bladder Cancer, 15 September 2014.
  19. Nippon Kayaku Co., Ltd. Combination Therapy With NC-6004 and Gemcitabine Versus Gemcitabine Alone inPancreatic Cancer, 15 April 2020.
  20. Novavax Inc. U.S. Food & Drug. Drug Approval Package: Estrasorb (Estradiol) Topical Emulsion, 9 October 2003.
  21. Nippon Kayaku Co., Ltd. Study of NK012 in Patients With Refractory Solid Tumors, 12 October 2007.
  22. SK M. Nanoparticles in modern medicine: state of the art and future challenges. International Journal of Nanomedicine, 2007, 2(2): 129-141.
  23. Varga-Bernal R. Introductory Chapter: Hybrid Nanomaterials, 10 June 2020.
  24. Dave V, Yadav RB, Kushwaha K, et al. Lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system. Bioactive Materials, 2017, 2(4): 269-280.
  25. Singh B, Saini S, Lohan S, et al. Nanotechnology-Based Approaches for Targeting and Delivery of Drugs and Genes. 2017, 110-148.
  26. Jain K, Jain NK and Kesharwani P. Dendrimer-Based Nanotherapeutics, 2021, 95-123.
  27. Gupta U and Perumal O. Chapter 15 - Dendrimers and Its Biomedical Applications, December 2014.
  28. Rana S, Bhattacharjee J, Barick K, et al. Chapter 7 - Interfacial engineering of nanoparticles for cancer therapeutics. In In Micro and Nano Technologies, Nanostructures for Cancer Therapy, 2017.
  29. Koopaie M. 22 - Nanoparticulate systems for dental drug delivery. In Woodhead Publishing Series in Biomaterials, Nanoengineered Biomaterials for Advanced Drug Delivery, 2020.
  30. Manne LS. Encyclopedia of Physical Science and Technology (Third Edition), 2003.
  31. Ree BJ, Satoh T and Yamamoto T. Micelle Structure Details and Stabilities of Cyclic Block Copolymer Amphiphile and Its Linear Analogues. Polymers, 2019, 11(1): 163.
  32. Mlynarczyk D, Kocki T and Goslinski T. Dendrimer Structure Diversity and Tailorability as a Way to Fight Infectious Diseases, 12 July 2017.
  33. Soares D, Domingues S, Viana D, et al. Polymer-hybrid nanoparticles: Current advances in biomedical applications. Biomedicine & Pharmacotherapy, 2020, 131: 110695.
  34. Kurtoglu YE, Mishra MK, Kannan S, et al. Drug release characteristics of PAMAM dendrimer-drug conjugates with different linkers. International Journal of Pharmaceutics, 2010, 384(1-2): 189-194.
  35. Tekade RK, Dutta T, Gajbhiye V, et al. Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics. Journal of Microencapsulation, 2009, 26(4): 287-296.
  36. Zhou DZ, Ma DX, Murphy DCJ, et al. Molecularly Precise Dendrimer-Drug Conjugates with Tunable Drug Release for Cancer Therapy. Angewandte Chemie, 2014, 134(42): 11129-111135.
  37. Hu H, F X and Cao Z. Thermo- and pH-sensitive dendrimer derivatives with a shell of poly(N,N-dimethylaminoethyl methacrylate) and study of their controlled drug release behavior. Polymer, 2005, 46(22): 9514-9522.
  38. Attwood D and D'Emanuele A. Dendrimer-drug interactions. Advanced Drug Delivery Reviews, 2005, 57(15): 2147-2162.
  39. Thanh VM, Nguyen TH, Tran TV, et al. Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release. Materials Science and Engineering: C, 2018, 82: 291-298.
  40. Zhang M, Zhu J, Zheng Y, et al. Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy. Pharmaceutics, 2018, 10(3): 162.
  41. Vembu S, Pazhamalai S and Gopalakrishnan M. Potential antibacterial activity of triazine dendrimer: Synthesis and controllable drug release properties. Bioorganic & Medicinal Chemistry, 2015, 23(15): 4561-4566.
  42. Wang J, He H, Cooper RC, et al. Drug Release via a Self-Cleaving Mechanism. Molecular Pharmaceutics, 2019, 16(5): 1874-1880.
  43. Mehta D, Leong N, Mcleod VM, et al. Reducing Dendrimer Generation and PEG Chain Length Increases Drug Release and Promotes Anticancer Activity of PEGylated Polylysine Dendrimers Conjugated with Doxorubicin via a Cathepsin-Cleavable Peptide Linker. Molecular Pharmaceutics, 2018, 15(10): 4568-4576.
  44. Wu SY, Chou HY, Yuh CH, et al. Radiation-Sensitive Dendrimer-Based Drug Delivery System. Advanced Science, 2018, 5(2): 1700339.
  45. Dai XH, Zhang HD and Dong CM. Fabrication, biomolecular binding, in vitro drug release behavior of sugar-installed nanoparticles from star poly($varepsilon$-caprolactone)/glycopolymer biohybrid with a dendrimer core. Polymer, 2009, 500(19): 4626-4634.
  46. Moghimi HR, Zarghi A, Mahboubi A, et al. PAMAM-dendrimer Enhanced Antibacterial Effect of Vancomycin Hydrochloride Against Gram-Negative Bacteria. Journal of Pharmacy & Pharmaceutical Sciences, 2018, 22(1): 10-21.
  47. Choi SK, Myc A, Silpe JE, et al. Dendrimer-Based Multivalent Vancomycin Nanoplatform for Targeting the Drug-Resistant Bacterial Surface. ACS Nano, 2013, 7(1): 214-228.
  48. Sonawane SJ, Kalhpure RS, Rambharose S, et al. Ultra-small lipid-dendrimer hybrid nanoparticles as a promising strategy for antibiotic delivery: In vitro and in silico studies. International Journal of Pharmaceutics, 2016, 504(1-2): 1-10.
  49. Chang Y, Meng X, Zhao Y, et al. Novel water-soluble and pH-responsive anticancer drug nanocarriers: Doxorubicin-PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles (IONPs). Journal of Colloid and Interface Science, 2011, 363(1): 403-409.
  50. Golshan M, Salami-Kalajahl M, Roghani-Mamaqani H, et al. Poly(propylene imine) dendrimer-grafted nanocrystalline cellulose: Doxorubicin loading and release behavior. Polymer, 20017, 117: 287-294.
  51. Lee SJ, Jeong YI, Park HK, et al. Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery. International Journal of Nanomedicine, 2015, 10(1): 5489-5503.
  52. Khutale GV and Casey A. Synthesis and characterization of a multifunctional gold-doxorubicin nanoparticle system for pH triggered intracellular anticancer drug release. European Journal of Pharmaceutics and Biopharmaceutics, 2017, 119: 372-380.
  53. Golshan M, Salami-Kalajahl M, Mirshekarpour M, et al. Synthesis and characterization of poly(propylene imine)-dendrimer-grafted gold nanoparticles as nanocarriers of doxorubicin. Colloids and Surfaces B: Biointerfaces, 2017, 155: 257-265.
  54. Zhang M, Guo R, Keri M, et al. Impact of Dendrimer Surface Functional Groups on the Release of Doxorubicin from Dendrimer Carriers. The Journal of Physical Chemistry B, 2014, 118(6): 1696-1706.
  55. Hong DW, Lai PL, Ku KL, et al. Biodegradable in situ gel-forming controlled vancomycin delivery system based on a thermosensitive mPEG-PLCPPA hydrogel. Polymer Degradation and Stability, 2013, 98(9): 1578-1585.
  56. Kim SY, Shin IG, Lee YM, et al. Methoxy poly(ethylene glycol) and $varepsilon$-caprolactone amphiphilic block copolymeric micelle containing indomethacin.: II. Micelle formation and drug release behaviours. Journal of Controlled Release, 1998, 51(1): 13-22.
  57. Chen W, Zhong P, Meng F, et al. Redox and pH-responsive degradable micelles for dually activated intracellular anticancer drug release. Journal of Controlled Release, 2013, 169(3): 171-179.
  58. Sun P, Zhou D and Gan Z. Novel reduction-sensitive micelles for triggered intracellular drug release. Journal of Controlled Release, 2011, 155(1): 96-103.
  59. Chen W, Meng F, Li F, et al. pH-Responsive Biodegradable Micelles Based on Acid-Labile Polycarbonate Hydrophobe: Synthesis and Triggered Drug Release. Biomacromolecules, 2009, 10(7): 1727-1735.
  60. Li Q, Yao W, Zhang B, et al. Drug-loaded pH-responsive polymeric micelles: Simulations and experiments of micelle formation, drug loading and drug release. Colloids and Surfaces B: Biointerfaces, 2017, 158: 709-716.
  61. Liu H, Farrell S and Uhrich K. Drug release characteristics of unimolecular polymeric micelles. Journal of Controlled Release, 2000, 68(2): 167-174.
  62. Ponta A and Bae Y. PEG-poly(amino acid) Block Copolymer Micelles for Tunable Drug Release. Pharmaceutical Research, 2010, 27: 2330-2342.
  63. Lin J, Zhu J, Chen T, et al. Drug releasing behavior of hybrid micelles containing polypeptide triblock copolymer. Biomaterials, 2009, 30(1): 108-117.
  64. Chen W, Meng F, Cheng R, et al. Facile construction of dual-bioresponsive biodegradable micelles with superior extracellular stability and activated intracellular drug release. Journal of Controlled Release, 2015, 210: 125-133.
  65. Wang W, Sun H, Meng F, et al. Precise control of intracellular drug release and anti-tumor activity of biodegradable micellar drugsvia reduction-sensitive shell-shedding. Soft Matter, 2012, 8: 3949-3956.
  66. Chen M, Xie S, Wei J, et al. Antibacterial Micelles with Vancomycin-Mediated Targeting and pH/Lipase-Triggered Release of Antibiotics. ACS Applied Materials & Interfaces, 2018, 10(43): 36814-36823.
  67. Cong Y, Quan C, Liu M, et al. Alendronate decorated biodegradable polymeric. Journal of Biomaterials Science, Polymer Edition, 2015, 26(11): 629-643.
  68. Chartpitak T, Tulakarnwong S, Riansuwan K, et al. Vancomycin-impregnated polymer on Schanz pin for prolonged release and antibacterial application. Journal of Drug Delivery Science and Technology, 2018, 47: 223-229.
  69. Jahan F, Zaman SU, Arshad R, et al. Mapping the potential of thiolated pluronic based nanomicelles for the safe. Journal of Drug Delivery Science and Technology, 2021, 61: 102220.
  70. Li S, Wu W, Xiu K, et al. Doxorubicin Loaded pH-Responsive Micelles Capable of Rapid Intracellular Drug Release for Potential Tumor Therapy. Journal of Biomedical Nanotechnology, 2014, 10(8): 1480-1489.
  71. Ye YQ, Yang FL, Hu FQ, et al. Core-modified chitosan-based polymeric micelles for controlled release of doxorubicin. International Journal of Pharmaceutics, 2008, 352(1-2): 294-301.
  72. Xu C, Song RJ, Lu P, et al. pH-triggered charge-reversal and redox-sensitive drug release polymer micelles co-deliver doxorubicin and triptolide for prostate tumor therapy. International Journal of Nanomedicine, 2018, 13: 7229-7249.
  73. Sun H, Guo B, Cheng R, et al. Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials, 2009, 30(31): 6358-6366.
  74. Birhan YS, Darge HF, Hanurry EY, et al. Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release. Pharmaceutics, 2020, 12(6): 580.
  75. Galbreath S, Krueger B, Frazier T, et al. Effectiveness of mesoporous bioglass in drug delivery. Journal of Pharmaceutical and Biopharmaceutical Research, 2022, 4(1): 271-282.
  76. Cao D, Zhang X, Akabar M, et al. Liposomal doxorubicin loaded PLGA-PEG-PLGA based thermogel for sustained local drug delivery for the treatment of breast cancer. Artificial Cells, Nanomedicine, and Biotechnology, 2019, 47(1): 181-191.
  77. Li M, Tang Z, Lin J, et al. Synergistic Antitumor Effects of Doxorubicin-Loaded Carboxymethyl Cellulose Nanoparticle in Combination with Endostar for Effective Treatment of Non-Small-Cell Lung Cancer. Advanced Healthcare Materials, 2014, 3(11): 1877-1888.
  78. Prabha G and Raj V. Sodium alginate-polyvinyl alcohol-bovin serum albumin coated Fe3O4 nanoparticles as anticancer drug delivery vehicle: Doxorubicin loading and in vitro release study and cytotoxicity to HepG2 and L02 cells. Materials Science and Engineering: C, 2017, 79: 410-422.
  79. Rahman MS, Tahir MA, Noreen S, et al. Osteogenic silver oxide doped mesoporous bioactive glass for controlled release of doxorubicin against bone cancer cell line (MG-63): In vitro and in vivo cytotoxicity evaluation. Ceramics International, 2020, 46(8): 10765-10770.
  80. Bayda S, Adeel M, Tuccinardi T, et al. The History of Nanoscience and Nanotechnology: From Chemical-Physical Applications to Nanomedicine. Molecules, 2020, 25(1): 112.
  81. Paradise M and Goswami T. Carbon Nanotubes -- Production and Industrial Applications. Materials and Design, 2007, 28(5): 1477-1489.
  82. Brooks Z, Goswami T, Doll A, et al. Transdermal drug dlivery systems: Analysis of adhesion failure. Journal of Pharmaceutical and Biopharmaceutical Research, 2022, 4(1): 2022, 256-270.
  83. Assani k, Doll a and Goswami T. Mechanical Properties of nanoparticles in drug delivery kinetics. Journal of Pharmaceutical and Biopharmaceutical Research, 2022, 4(1): 248-255.