In vitro biocompatibility and bioactivity of microencapsulated heparan sulfate.
The glycosaminoglycan sugar heparan sulfate (HS) is an attractive agent for the repair of bone defects due to its ability to regulate endogenous growth factors. The sustained delivery of HS to the localized wound site over the period of healing which can last for over 1 month may prove advantageous for its therapeutic use. In this study we investigated the encapsulation of HS by the water-in oil-in water (W(1)/O/W(2)) technique in polycaprolactone (PCL) microcapsules as a prolonged delivery device. Encapsulation efficiencies of 70% could be achieved by using a 1:1 mixture of dichloromethane (DCM) and acetone as the solvent in the organic phase, while DCM alone gave poor encapsulation. Although addition of polyvinyl alcohol (PVA) to the drug phase did not affect the size or drug loading of the microcapsules, it did however produce a large change in the morphology and drug distribution, which resulted in different release rates. Release from capsules made with PVA in the drug phase reached 60% after 40 days, while those made with water in the drug phase completed release after 20 days. In vitro biocompatibility studies were performed and detected no increase in cell death in human mesenchymal stem cells (hMSC) or induction of an inflammatory response in macrophages after exposure to release products from HS-loaded microcapsules. The released HS retained its ability to increase the proliferation of hMSC after the encapsulation process. These results indicate that encapsulation of HS by the W(1)/O/W(2) method creates a promising device for the repair of bone tissue.
Luong-Van
Emma
E
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
Grøndahl
Lisbeth
L
Nurcombe
Victor
V
Cool
Simon
S
D000818:Animals; D001672:Biocompatible Materials; D002478:Cells, Cultured; D004339:Drug Compounding; D017102:Fracture Healing; D006497:Heparan Sulfate / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008855:Microscopy, Electron, Scanning
D001672:Biocompatible Materials; D006497:Heparan Sulfate