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A new insight into encapsulation process of a drug molecule in the polymer/surfactant system: a molecular simulation study

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Abstract

Drug delivery plays a substantial role in a more effective treatment of diseases of the central nervous system; therefore, the selection of an appropriate drug carrier system is very important to enhance the effectiveness of drugs. Due to the effect of surfactant on improvement of polymer performance in drug-carrying systems, the present study was devoted to investigating the influence of Polysorbate 80 (Pst80) surfactant on poly(n-butylcyanoacrylate)(PBCA)/Tacrine and Chitosan/Tacrine drug-carrying systems from molecular point of view. Interaction energy, structural characterization, Flory–Huggins interaction parameter, and solvation free energy were investigated for both systems by employing molecular dynamics simulations. According to the interaction energy and Flory–Huggins parameter results, Pst80 can be a more suitable choice for targeted releasing of drug in PBCA/Tacrine system compared with Chitosan/Tacrine system because Pst80 firmly surrounded the drug carrier PBCA and Tacrine. Additionally, the solvation free energy results demonstrated more solubility of PBCA/Pst80/Tacrine in water medium compared with that of Chitosan/Pst80/Tacrine. By consideration on different solvation free energy contributions, it was concluded that using a polymer with both hydrophilic and hydrophobic parts, presence of functional groups with heavy atoms on both polymer and surfactant and similarity in chemical nature of hydrophobic parts of both polymer and surfactant can be useful approaches to reduce the total solvation free energy. Preparation of an appropriate solubility of polymer/drug in water/surfactant medium is essential to enhance drug delivery system efficiency and reduce waste of drug in human body, which can be achieved by designing a drug-carrying system with the minimum solvation free energy. This study confirms the significant role of molecular dynamics simulation for a detailed study of polymer/surfactant/dug systems and clarifies its effective role for designing novel drug delivery systems, along with saving time and cost.

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References

  1. Alam MI, Beg S, Samad A et al (2010) Strategy for effective brain drug delivery. Eur J Pharm Sci 40:385–403. https://doi.org/10.1016/j.ejps.2010.05.003

    Article  CAS  PubMed  Google Scholar 

  2. Chen Y, Liu L (2012) Modern methods for delivery of drugs across the blood-brain barrier. Adv Drug Deliv Rev 64:640–665. https://doi.org/10.1016/j.addr.2011.11.010

    Article  CAS  PubMed  Google Scholar 

  3. Silva GA (2008) Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS. BMC Neurosci 2008(9):1–4. https://doi.org/10.1186/1471-2202-9-S3-S4

    Article  CAS  Google Scholar 

  4. De Rosa G, Salzano G, Caraglia M, Abbruzzese A (2012) Nanotechnologies: a strategy to overcome blood-brain barrier. Curr Drug Metab 13:61–69

    Article  PubMed  Google Scholar 

  5. Huynh GH, Deen DF, Szoka FC (2006) Barriers to carrier mediated drug and gene delivery to brain tumors. J Control Release 110:236–259. https://doi.org/10.1016/j.jconrel.2005.09.053

    Article  CAS  PubMed  Google Scholar 

  6. Ferri CP, Prince M, Brayne C et al (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366:2112–2117

    Article  PubMed  PubMed Central  Google Scholar 

  7. Anand R, Gill KD, Mahdi AA (2014) Therapeutics of Alzheimer’s disease: Past, present and future. Neuropharmacology 76:27–50. https://doi.org/10.1016/j.neuropharm.2013.07.004

    Article  CAS  PubMed  Google Scholar 

  8. Contestabile A (2011) The history of the cholinergic hypothesis. Behav Brain Res 221:334–340. https://doi.org/10.1016/j.bbr.2009.12.044

    Article  CAS  PubMed  Google Scholar 

  9. Tumiatti V, Minarini A, Bolognesi ML, et al (2010) Tacrine derivatives and Alzheimer’ s disease. Curr Med Chem 1825–1838

  10. Faraji AH, Wipf P (2009) Bioorganic & Medicinal Chemistry Nanoparticles in cellular drug delivery. Bioorg Med Chem 17:2950–2962. https://doi.org/10.1016/j.bmc.2009.02.043

    Article  CAS  PubMed  Google Scholar 

  11. Patel MP, Patel RR, Patel JK (2010) Chitosan mediated targeted drug delivery system: a review. J Pharm Pharm Sci 13:536–557

    Article  CAS  PubMed  Google Scholar 

  12. Wilson B (2009) Brain targeting PBCA nanoparticles and the blood-brain barrier. Nanomedicine 4:499–502. https://doi.org/10.2217/nnm.09.29

    Article  CAS  PubMed  Google Scholar 

  13. Wilson B, Samanta MK, Santhi K et al (2010) Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomed Nanotechnol Biol Med 6:144–152. https://doi.org/10.1016/j.nano.2009.04.001

    Article  CAS  Google Scholar 

  14. Wilson B, Samanta MK, Santhi K et al (2008) Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles. Eur J Pharm Biopharm 70:75–84. https://doi.org/10.1016/j.ejpb.2008.03.009

    Article  CAS  PubMed  Google Scholar 

  15. Zhang H, Yao M, Morrison RA, Chong S (2003) Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Arch Pharm Res 26:768–772

    Article  CAS  PubMed  Google Scholar 

  16. Martln-Algarra RV, Pascual-Costa RM, Merino M, Casabó VG (1995) Effects of polysorbate 80 on amiodarone intestinal absorption in the rat. Int J Pharm 122:1–8

    Article  Google Scholar 

  17. Bender EA, Adorne MD, Colomé LM et al (2012) with polysorbate 80-lecithin and uncoated or coated with chitosan. Int J Pharm 426:271–279. https://doi.org/10.1016/j.ijpharm.2012.01.051

    Article  CAS  PubMed  Google Scholar 

  18. Gao K, Jiang X (2006) Influence of particle size on transport of methotrexate across blood brain barrier by polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Int J Pharm 310:213–219. https://doi.org/10.1016/j.ijpharm.2005.11.040

    Article  CAS  PubMed  Google Scholar 

  19. Wang Y, Wang C, Gong C et al (2012) Polysorbate 80 coated poly (?-caprolactone)–poly (ethylene glycol)–poly (?-caprolactone) micelles for paclitaxel delivery. Int J Pharm 434:1–8. https://doi.org/10.1016/j.ijpharm.2012.05.015

    Article  CAS  PubMed  Google Scholar 

  20. Sakane T, Tanaka C, Yamamoto A et al (1989) The effect of polysorbate 80 on brain uptake and analgesic effect of D-kyotorphin. Int J Pharm 57:77–83

    Article  CAS  Google Scholar 

  21. Cappel MJ, Jorg K (1991) Effect of nonionic surfactants on transdermal drug delivery: I. Polysorbates. Int J Pharm 69:143–153

    Article  CAS  Google Scholar 

  22. Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA (1995) Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Res 674(674):171–174

    Article  CAS  PubMed  Google Scholar 

  23. Macháčková M, Tokarský J, Capková P (2013) A simple molecular modeling method for the characterization of polymeric drug carriers. Eur J Pharm Sci 48:316–322. https://doi.org/10.1016/j.ejps.2012.11.010

    Article  CAS  PubMed  Google Scholar 

  24. Viceconti M, Henney A, Morley-Fletcher E (2016) In silico clinical trials : how computer simulation will transform the biomedical industry. Int J. Clin Trials 3:37–46. https://doi.org/10.18203/2349-3259.ijct20161408

    Article  Google Scholar 

  25. Mahmoudzadeh M, Fassihi A, Dorkoosh F et al (2015) Elucidation of molecular mechanisms behind the self-assembly behavior of chitosan amphiphilic derivatives through experiment and molecular modeling elucidation of molecular mechanisms behind the self-assembly behavior of chitosan amphiphilic derivatives T. Pharm Res 32:3899–3915. https://doi.org/10.1007/s11095-015-1750-y

    Article  CAS  PubMed  Google Scholar 

  26. Rungnim C, Rungrotmongkol T, Hannongbua S, Okumura H (2013) Journal of Molecular Graphics and Modelling Replica exchange molecular dynamics simulation of chitosan for drug delivery system based on carbon nanotube. J Mol Graph Model 39:183–192. https://doi.org/10.1016/j.jmgm.2012.11.004

    Article  CAS  PubMed  Google Scholar 

  27. Eslami M, Nikkhah SJ, Hashemianzadeh SM, Sajadi SAS (2015) The compatibility of Tacrine molecule with poly(n-butylcyanoacrylate) and Chitosan as efficient carriers for drug delivery: a molecular dynamics study. Eur J Pharm Sci 82:79–85. https://doi.org/10.1016/j.ejps.2015.11.014

    Article  CAS  PubMed  Google Scholar 

  28. Plimpton S (1995) Fast parallel algorithms for short-range molecular dynamics. J Comput Phys 117:1–19

    Article  CAS  Google Scholar 

  29. Sun H (1995) Ab initio calculations and force field development for computer simulation of polysilanes. Macromolecules 28:701–712

    Article  CAS  Google Scholar 

  30. Sun H, Mumby SJ, Maple JR, Hagler AT (1994) An ab initio CFF93 all-atom force field for polycarbonates. J Am Chem Soc 116:2978–2987. https://doi.org/10.1021/ja00086a030

    Article  CAS  Google Scholar 

  31. Sun H (1998) COMPASS: an ab initio force-field optimized for condensed-phase applications-overview with details on alkane and benzene compounds. J Phys Chem 5647:7338–7364. https://doi.org/10.1021/jp980939v

    Article  Google Scholar 

  32. Ewald PP (1921) Die Berechnung optischer und elektrostatischer Gitterpotentiale. Ann Phys 369:253–287

    Article  Google Scholar 

  33. Lobanov MY, Bogatyreva NS, Galzitskaya OV (2008) Radius of gyration as an indicator of protein structure compactness. Mol Biol 42:701–706. https://doi.org/10.1134/S0026893308040195

    Article  CAS  Google Scholar 

  34. Repakova J, Capkova P, Studenovsky M, Ilavsky M (2004) Characterization of molecular structures and properties of polyurethanes using molecular dynamics simulations. J Mol Model 10:240–249. https://doi.org/10.1007/s00894-004-0187-8

    Article  CAS  PubMed  Google Scholar 

  35. Pajula K, Taskinen M, Lehto VP et al (2010) Predicting the formation and stability of amorphous small molecule binary mixtures from computationally determined Flory-Huggins interaction parameter and phase diagram. Mol Pharm 7:795–804. https://doi.org/10.1021/mp900304p

    Article  CAS  PubMed  Google Scholar 

  36. Frenkel D, Smit B (2002) Understanding molecular simulation: from algorithms to applications. https://doi.org/10.1063/1.881812

  37. McQuarrie DA (2000) Statistical mechanics. University Science Books, Saucilito

    Google Scholar 

  38. Dolenc J, Oostenbrink C, Koller J, van Gunsteren W (2005) Molecular dynamics simulations and free energy calculations of netropsin and distamycin binding to an AAAAA DNA binding site. Nucleic Acids Res 33:725–733. https://doi.org/10.1093/nar/gki195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Redmill PS, Capps SL, Cummings PT, Mccabe C (2009) A molecular dynamics study of the Gibbs free energy of solvation of fullerene particles in octanol and water. Carbon N Y 47:2865–2874. https://doi.org/10.1016/j.carbon.2009.06.040

    Article  CAS  Google Scholar 

  40. Mccabe C, Galindo A, Cummings PT (2003) Anomalies in the solubility of alkanes in near-critical water. J Phys Chem B 107:12307–12314

    Article  CAS  Google Scholar 

Download references

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Author notes

  1. Mahboobeh Eslami and Sousa Javan Nikkhah contributed equally to this work.

Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mahboobeh Eslami

  2. School of Chemical Engineering, Iran University of Science and Technology (IUST), Tehran, Iran

    Sousa Javan Nikkhah

  3. Department of Chemical Engineering, Shahreza Branch, Islamic Azad University, Shahreza, Iran

    Elham Eslami

  4. Molecular Simulation Research Laboratory, Department of Chemistry, Iran University of Science and Technology (IUST), Tehran, Iran

    Seyed Majid Hashemianzadeh

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  1. Mahboobeh Eslami
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  3. Elham Eslami
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  4. Seyed Majid Hashemianzadeh
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Correspondence to Mahboobeh Eslami.

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Eslami, M., Nikkhah, S.J., Eslami, E. et al. A new insight into encapsulation process of a drug molecule in the polymer/surfactant system: a molecular simulation study. Struct Chem 31, 2051–2062 (2020). https://doi.org/10.1007/s11224-020-01550-8

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  • DOI: https://doi.org/10.1007/s11224-020-01550-8

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