May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Sustained Delivery of Proteins From Alginate Microspheres
Author Affiliations & Notes
  • L.A. Wells
    Chemical Engineering, McMaster University, Hamilton, ON, Canada
  • H. Sheardown
    Chemical Engineering, McMaster University, Hamilton, ON, Canada
  • Footnotes
    Commercial Relationships  L.A. Wells, None; H. Sheardown, None.
  • Footnotes
    Support  NSERC
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5125. doi:
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      L.A. Wells, H. Sheardown; Sustained Delivery of Proteins From Alginate Microspheres . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5125.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Ophthalmic sustained delivery systems with high resident times will help increase corneal delivery of molecules. High viscosity solutions help to lower the clearance of the delivery device by reducing its elimination by tear fluid. The use of alginate, a high viscosity, natural polymer, as a delivery system was investigated using a novel encapsulation method for proteins with varying charge properties.

Methods: : Albumin, lysozyme and chymotrypsin were encapsulated in the alginate spheres through soaking of freeze–dried and swollen alginate microspheres in a degradative protein–containing NaCl solution, followed by their re–crosslinking with calcium chloride to "lock" the protein into the alginate matrix. The encapsulation procedure was optimized, and followed by release studies into phosphate buffered saline, TRIS buffered saline or low concentration sodium chloride. The biological activity of released proteins was assessed.

Results and Discussion: : High pI proteins appeared to physically crosslink the sodium alginate; therefore they were loaded into spheres using the novel degradative–based technique. Using this method, quick encapsulations were achieved with over twice as much lysozyme and chymotrypsin encapsulated versus albumin. Release studies showed albumin released quickly into all media independent of loading technique. In TBS, chymotrypsin and lysozyme showed sustained release lasting over 150 hours. Release into NaCl further sustained the release of lysozyme to more than 2000 hours with reduced volume medium lengthening the release to past 6 months. Released lysozyme was shown to remain active with some data showing activity over 100% of the active control.

Conclusions: : The novel encapsulation technique can be used to rapidly load alginate microspheres, limiting potential degradation of proteins in solution. Both the charge of the protein and its release media were found to play an important role in the kinetics of release with electropositive proteins acting to slow alginate degradation. This system may be exploited for delivery of drugs to the eye; the presence of lysozyme in tear fluid may reduce the degradation rate of alginate making it a long–resident time drug delivery vehicle with the potential for crosslinking in situ.

Keywords: pharmacology • enzymes/enzyme inhibitors • cornea: basic science 

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