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Computer-Aided Design of Nanoparticles for Transdermal Drug Delivery

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Drug Delivery Systems

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2059))

Abstract

Human skin provides an excellent opportunity for drug delivery application. However, the delivery of hydrophilic drug and big protein molecules is challenging due to barrier provided by the top layer of skin known as stratum corneum (SC). The chemical permeation enhancers or specialized carriers such as nanoparticles (NPs) are needed which can deliver drug molecules into the deeper layer.

Here, we describe the in silico design of nanoparticle carriers using molecular dynamics (MD) simulations for the transdermal drug delivery application. At first, setup of a skin lipid bilayer model is demonstrated. Further, nanoparticles are designed based on the Monte Carlo simulation technique. These nanoparticles are then tested on skin model using various MD simulation techniques.

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References

  1. Naik A, Kalia Y, Guy R (2000) Transdermal drug delivery: overcoming the skin’s barrier function. Pharm Sci Technol Today 3:318–326. https://doi.org/10.1016/s1461-5347(00)00295-9

    Article  CAS  PubMed  Google Scholar 

  2. Michaels A, Chandrasekaran S, Shaw J (1975) Drug permeation through human skin: Theory and in vitro experimental measurement. AICHE J 21:985–996. https://doi.org/10.1002/aic.690210522

    Article  CAS  Google Scholar 

  3. Elias P (1983) Epidermal Lipids, Barrier Function, and Desquamation. J Investig Dermatol 80:44s–49s. https://doi.org/10.1038/jid.1983.12

    Article  CAS  PubMed  Google Scholar 

  4. Bouwstra J, Ponec M (2006) The skin barrier in healthy and diseased state. Biochim Biophys Acta Biomembr 1758:2080–2095. https://doi.org/10.1016/j.bbamem.2006.06.021

    Article  CAS  Google Scholar 

  5. Vitorino C, Almeida A, Sousa J et al (2014) Passive and active strategies for transdermal delivery using co-encapsulating nanostructured lipid carriers: In vitro vs. in vivo studies. Eur J Pharm Biopharm 86:133–144. https://doi.org/10.1016/j.ejpb.2013.12.004

    Article  CAS  PubMed  Google Scholar 

  6. Mathur V, Satrawala Y, Rajput M (2010) Physical and chemical penetration enhancers in transdermal drug delivery system. Asian J Pharm 4:173. https://doi.org/10.4103/0973-8398.72115

    Article  CAS  Google Scholar 

  7. Karande P, Jain A, Ergun K et al (2005) Design principles of chemical penetration enhancers for transdermal drug delivery. Proc Natl Acad Sci 102:4688–4693. https://doi.org/10.1073/pnas.0501176102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Karande P, Mitragotri S (2009) Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta Biomembr 1788:2362–2373. https://doi.org/10.1016/j.bbamem.2009.08.015

    Article  CAS  Google Scholar 

  9. Huang Y, Yu F, Park Y et al (2010) Co-administration of protein drugs with gold nanoparticles to enable percutaneous delivery. Biomaterials 31:9086–9091. https://doi.org/10.1016/j.biomaterials.2010.08.046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gupta R, Rai B (2016) Penetration of Gold Nanoparticles through Human Skin: Unraveling Its Mechanisms at the Molecular Scale. J Phys Chem B 120:7133–7142. https://doi.org/10.1021/acs.jpcb.6b03212

    Article  CAS  PubMed  Google Scholar 

  11. Labouta H, El-Khordagui L, Kraus T, Schneider M (2011) Mechanism and determinants of nanoparticle penetration through human skin. Nanoscale 3:4989. https://doi.org/10.1039/c1nr11109d

    Article  CAS  PubMed  Google Scholar 

  12. Allen MP, Tildesley DJ (2017) Computer simulation of liquids. Oxford University Press, Oxford

    Book  Google Scholar 

  13. Oostenbrink C, Villa A, Mark A, Van Gunsteren W (2004) A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem 25:1656–1676. https://doi.org/10.1002/jcc.20090

    Article  CAS  PubMed  Google Scholar 

  14. Jorgensen W, Maxwell D, Tirado-Rives J (1996) Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. J Am Chem Soc 118:11225–11236. https://doi.org/10.1021/ja9621760

    Article  CAS  Google Scholar 

  15. Wang J, Wolf R, Caldwell J et al (2004) Development and testing of a general amber force field. J Comput Chem 25:1157–1174. https://doi.org/10.1002/jcc.20035

    Article  CAS  PubMed  Google Scholar 

  16. Vanommeslaeghe K, Hatcher E, Acharya C et al (2009) CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. https://doi.org/10.1002/jcc.21367

  17. Berger O, Edholm O, Jähnig F (1997) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J 72:2002–2013. https://doi.org/10.1016/s0006-3495(97)78845-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Marrink S, de Vries A, Mark A (2004) Coarse Grained Model for Semiquantitative Lipid Simulations. J Phys Chem B 108:750–760. https://doi.org/10.1021/jp036508g

    Article  CAS  Google Scholar 

  19. Marrink S, Risselada H, Yefimov S et al (2007) The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations. J Phys Chem B 111:7812–7824. https://doi.org/10.1021/jp071097f

    Article  CAS  PubMed  Google Scholar 

  20. Materials Studio. Accelrys Software Inc. http://accelrys.com/products/collaborative-science/biovia-materials-studio/

  21. Case D, Cheatham T, Darden T et al (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668–1688. https://doi.org/10.1002/jcc.20290. http://ambermd.org/GetAmber.php

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4:435–447. https://doi.org/10.1021/ct700301q. http://www.gromacs.org/

    Article  CAS  PubMed  Google Scholar 

  23. Plimpton S, Crozier P, Thompson A (2007) LAMMPS-large-scale atomic/molecular massively parallel simulator. Sandia Natl Lab 18:43–43. http://lammps.sandia.gov/

    Google Scholar 

  24. Phillips J, Braun R, Wang W et al (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26:1781–1802. https://doi.org/10.1002/jcc.20289. http://www.ks.uiuc.edu/Research/namd/

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Brooks B, Bruccoleri R, Olafson B et al (1983) CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 4:187–217. https://doi.org/10.1002/jcc.540040211. https://www.charmm.org/charmm

    Article  CAS  Google Scholar 

  26. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14:33–38. https://doi.org/10.1016/0263-7855(96)00018-5. http://www.ks.uiuc.edu/Research/vmd/

    Article  CAS  PubMed  Google Scholar 

  27. Coderch L, Lopez O, de la Maza A, Parra J (2003) Ceramides and skin function. Am J Clin Dermatol 4:107–129. https://doi.org/10.2165/00128071-200304020-00004

    Article  PubMed  Google Scholar 

  28. Gupta R, Dwadasi B, Rai B (2016) Molecular dynamics simulation study of permeation of molecules through skin lipid bilayer. J Phys Chem B 120:8987–8996. https://doi.org/10.1021/acs.jpcb.6b05451

    Article  CAS  PubMed  Google Scholar 

  29. Gupta R, Dwadasi B, Rai B (2016) Molecular dynamics simulation of skin lipids: effect of ceramide chain lengths on bilayer properties. J Phys Chem B 120:12536–12546. https://doi.org/10.1021/acs.jpcb.6b08059

    Article  CAS  PubMed  Google Scholar 

  30. Guo S, Moore T, Iacovella C et al (2013) Simulation study of the structure and phase behavior of ceramide bilayers and the role of lipid headgroup chemistry. J Chem Theory Comput 9:5116–5126. https://doi.org/10.1021/ct400431e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Martínez L, Andrade R, Birgin E, Martínez J (2009) PACKMOL: a package for building initial configurations for molecular dynamics simulations. J Comput Chem 30:2157–2164. https://doi.org/10.1002/jcc.21224

    Article  CAS  PubMed  Google Scholar 

  32. Gupta R, Rai B (2017) Molecular dynamics simulation study of translocation of fullerene C60through skin bilayer: effect of concentration on barrier properties. Nanoscale 9:4114–4127. https://doi.org/10.1039/c6nr09186e

    Article  CAS  PubMed  Google Scholar 

  33. Gupta R, Kashyap N, Rai B (2017) Transdermal cellular membrane penetration of proteins with gold nanoparticles: a molecular dynamics study. Phys Chem Chem Phys 19:7537–7545

    Article  CAS  PubMed  Google Scholar 

  34. Gupta R, Rai B (2018) In-silico design of nanoparticles for transdermal drug delivery application. Nanoscale 10:4940–4951

    Article  CAS  PubMed  Google Scholar 

  35. Gupta R, Rai B (2017) Effect of size and surface charge of gold nanoparticles on their skin permeability: a molecular dynamics study. Sci Rep 7:45292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Berman H (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242. https://doi.org/10.1093/nar/28.1.235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. http://www.cgmartini.nl/index.php/tools2/proteins-andbilayers/204-martinize

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Authors and Affiliations

  1. Physical Science Research Area, TCS Research, Tata Research Development and Design Centre, Tata Consultancy Services, Pune, Maharashtra, India

    Rakesh Gupta & Beena Rai

Authors
  1. Rakesh Gupta
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  2. Beena Rai
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Corresponding author

Correspondence to Beena Rai .

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Editors and Affiliations

  1. Jain PharmaBiotech, Basel, Switzerland

    Kewal K. Jain

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Gupta, R., Rai, B. (2020). Computer-Aided Design of Nanoparticles for Transdermal Drug Delivery. In: Jain, K. (eds) Drug Delivery Systems. Methods in Molecular Biology, vol 2059. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9798-5_12

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  • DOI: https://doi.org/10.1007/978-1-4939-9798-5_12

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9797-8

  • Online ISBN: 978-1-4939-9798-5

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