Shell cross-linked hyaluronic acid/polylysine layer-by-layer polyelectrolyte microcapsules prepared by removal of reducible hyaluronic acid microgel cores.

Hyukjin Lee, Yongho Jeong, Tae Gwan Park

Index: Biomacromolecules 8(12) , 3705-11, (2007)

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Abstract

Shell cross-linked hollow polyelectrolyte microcapsules composed of hyaluronic acid (HA) and poly- l-lysine (PLL) were prepared by layer-by-layer (LBL) adsorption and subsequent core removal by a reductive agent. Disulfide cross-linked HA microgels were used as template core materials for the LBL deposition on the surface and removed by treatment of dithiothreitol at neutral pH condition. HA/PLL polyelectrolyte multilayers on the shell were chemically cross-linked via carbodiimide chemistry, and their physicochemical properties and drug release behaviors were investigated. Shell cross-linked HA/PLL polyelectrolyte microcapsules exhibited far enhanced physical stability against freeze-thaw cycles and acidic pH conditions compared to the un-cross-linked ones. The cross-linked HA/PLL multilayer shell also demonstrated pH responsive permeability, which became more permeable at low pH than at neutral pH. When bovine serum albumin (BSA), as a model protein drug, was loaded inside using the pH-dependent permeability, BSA release profiles from the microcapsules could be readily modulated by varying medium pH values or adding an HA digesting enzyme (hyaluronidase) in the incubation medium.