Protein complexed with chondroitin sulfate in poly(lactide-co-glycolide) microspheres.
Chondroitin sulfate (CsA) is an acidic mucopolysaccharide, which is able to form ionic complexes with positively charged proteins. In this study, a protein-CsA complex was constructed to nano-sized particles. Zeta potential measurements revealed that a CsA-to-protein fraction of greater than 0.1 results in a neutralization of the positive charge on lysozyme (Lys). Based on this preliminary study, we have prepared poly(lactide-co-glycolide) (PLGA) microspheres harboring Lys/CsA complexes via the multi-emulsion method. Protein stability in the PLGA microspheres was preserved during both microsphere preparation and protein release. The profiles of Lys release from the PLGA microspheres evidenced nearly zero-order kinetics, depending on the quantity of CsA. An in vivo fluorescent image of experimental mouse tissue showed that the PLGA microspheres with the Lys/CsA complex had released the entirety of their Lys without no residual amount after 23 days, but microspheres without the complex harbored a great deal of residual Lys, which is attributable to its degradation by acidic PLGA degradates. The tissue reaction evidenced by the PLGA microspheres stabilized with CsA showed minimal foreign body reaction and little configuration of immune cells including neutrophils and macrophages, but the reactions of the PLGA microspheres without CsA were characterized by a relatively elevated inflammation. These results show that CsA is a viable candidate for long-acting micro-particular protein delivery.
Lee
Eun Seong
ES
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
Park
Keun-Hong
KH
Kang
Dongmin
D
Park
In Suh
IS
Min
Hyo Young
HY
Lee
Don Haeng
DH
Kim
Sungwon
S
Kim
Jong Ho
JH
Na
Kun
K
D000818:Animals; D002645:Chickens; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate; D005453:Fluorescence; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008837:Micrococcus / Q000166:cytology / Q000187:drug effects; D008863:Microspheres; D009113:Muramidase / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013816:Thermodynamics; D051598:Whole Body Imaging
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002809:Chondroitin Sulfates; D009113:Muramidase; D016650:Fluorescein-5-isothiocyanate