10.1186/2194-0517-2-3

An integrated experimental and modeling approach to propose biotinylated PLGA microparticles as versatile targeting vehicles for drug delivery

HTML PDF
  • Olivia Donaldson1,
  • Zuyi Jacky Huang1,
  • Noelle Comolli*1,
  1. Villanova University, Villanova, PA, 19085, US
Cover Image

Published in Issue 2013-02-13

How to Cite

Donaldson, O., Huang, Z. J., & Comolli, N. (2013). An integrated experimental and modeling approach to propose biotinylated PLGA microparticles as versatile targeting vehicles for drug delivery. Progress in Biomaterials, 2(1 (December 2013). https://doi.org/10.1186/2194-0517-2-3
Crossref
Scopus
Google Scholar
Europe PMC

Abstract

Abstract Polymeric microparticles with covalently attached biotin are proposed as versatile targeting vehicles for drug delivery. The proposed microparticles made of 85/15 poly (lactic- co -glycolic acid) (PLGA) will have biotin available on the outside of the particle for the further attachment with an avidin group. Taking advantage of biotin’s high affinity for avidin, and avidin’s well-known chemistry, the particle has the potential to be easily coated with a variety of targeting moieties. This paper focuses on the design and resulting effect of adding biotin to PLGA microparticles using an integrated experimental and modeling approach. A fluorescent-tagged avidin (488-streptavidin) was used to confirm the presence and bioavailability of biotin on the outside of the particles. For the purpose of this study, bovine serum albumin (BSA) was used as a model therapeutic drug. Microparticles were created using two different types of polyvinyl alcohol 88 and 98 mol% hydrolyzed, which were then analyzed for their size, morphology, and encapsulation capacity of BSA. Release studies performed in vitro confirmed the slow release of the BSA over a 28-day period. Based on these release profiles, a release kinetics model was used to further quantify the effect of biotinylation of PLGA microparticles on their release characteristics by quantitatively extracting the effective drug diffusivity and drug desorption rate from the release profiles. It was found that the biotinylation of the PLGA microparticles slowed down both the drug desorption and drug diffusion process, which confirmed that biotinylated PLGA microparticles can be used for controlled drug release. The presented technology, as well as the proposed integrated experimental and modeling approach, forms a solid foundation for future studies using a cell-specific ligand that can be attached to avidin and incorporated onto the microparticles for targeted delivery.

Keywords

  • Drug Release,
  • Biotin,
  • Mole Percentage,
  • Drug Release Profile,
  • PLGA Microparticle
HTML PDF

References

  1. Anderson and Shive (1997) Biodegradation and biocompatability of PLA and PLGA microspheres (pp. 5-24) https://doi.org/10.1016/S0169-409X(97)00048-3
  2. Balkwill (2004) The significance of cancer cell expression of the chemokine receptor CXCR4 14(3) (pp. 171-179) https://doi.org/10.1016/j.semcancer.2003.10.003
  3. Batycky et al. (1997) a theoretical model of erosion and macromolecular drug release from biodegrading microspheres 87(12) (pp. 1464-1477) https://doi.org/10.1021/js9604117
  4. Brannon-Peppas (1995) Recent advances on the use of biodegradable microparticles and nanoparticles in controlled drug delivery 116(1) (pp. 1-9) https://doi.org/10.1016/0378-5173(94)00324-X
  5. Brannon-Peppas and Blanchette (2004) Nanoparticle and targeted systems for cancer therapy 56(11) (pp. 1649-1659) https://doi.org/10.1016/j.addr.2004.02.014
  6. Cao and Shoichet (1998) Biodegradation and biocompatibility of PLA and PLGA microspheres (pp. 329-339) https://doi.org/10.1016/S0142-9612(98)00172-0
  7. Cleland and Sanders (1997) Protein delivery from biodegradable microspheres (pp. 1-25) Kluwer Academic
  8. Datta et al. (2006) Recognition based separation of HIV-Tat protein using avidin-biotin interaction in modified microfiltration membranes (pp. 298-310) https://doi.org/10.1016/j.memsci.2006.01.031
  9. Diamandis and Christopoulos (1991) The biotin-(strept)avidin system: principles and applications in biotechnology 37(5) (pp. 625-636)
  10. Dziubla et al. (2005) Polymer nanocarriers protecting active enzyme cargo against proteolysis 102(2) (pp. 427-439) https://doi.org/10.1016/j.jconrel.2004.10.017
  11. Folger et al. (2006) Inhibition of malarial topoisomerase II in Plasmodium falciparum by antisense nanoparticles 319(1–2) (pp. 139-146) https://doi.org/10.1016/j.ijpharm.2006.03.034
  12. Fung and Saltzman (1997) Polymeric implants for cancer chemotherapy 26(2–3) (pp. 209-230) https://doi.org/10.1016/S0169-409X(97)00036-7
  13. Kocbek et al. (2007) Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody 120(1–2) (pp. 18-26) https://doi.org/10.1016/j.jconrel.2007.03.012
  14. Moro et al. (1997) Tumor cell targeting with antibody-avidin complexes and biotinylated tumor necrosis factor alpha 57(10) (pp. 1922-1928)
  15. Muthu (2009) Nanoparticles based on PLGA and its co-polymer: an overview (pp. 266-273) https://doi.org/10.4103/0973-8398.59948
  16. Panyam et al. (2003) Polymer degradation and in vitro release of a model protein from poly(d, l-lactide-co-glycolide) nano- and microparticles 92(1–2) (pp. 173-187) https://doi.org/10.1016/S0168-3659(03)00328-6
  17. Park et al. (2011) Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates 156(1) (pp. 109-115) https://doi.org/10.1016/j.jconrel.2011.06.025
  18. Pegram et al. (1997) The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells 15(5) (pp. 537-547) https://doi.org/10.1038/sj.onc.1201222
  19. Putney (1998) Encapsulation of proteins for improved delivery (pp. 548-552) https://doi.org/10.1016/S1367-5931(98)80133-6
  20. Sayce et al. (2010) Targeting a host process as an antiviral approach against dengue virus 18(7) (pp. 323-330) https://doi.org/10.1016/j.tim.2010.04.003
  21. Shive and Anderson (1997) Biodegradation and biocompatibility of PLA and PLGA microspheres 28(1) (pp. 5-24) https://doi.org/10.1016/S0169-409X(97)00048-3
  22. Weiss et al. (2007) Coupling of biotin-(poly(ethylene glycol))amine to poly(d, l-lactide-co-glycolide) nanoparticles for versatile surface modification 18(4) (pp. 1087-1094) https://doi.org/10.1021/bc060342f