Preparation and characterization of ciliary neurotrophic factor sustained-release microcapsules / 中国组织工程研究

ABSTRACT

BACKGROUND:Conventional ophthalmic delivery of ciliary neurotrophic factor (CNTF) is extremely difficult to pass the blood-retinal barrier, resulting in a very low bioavailability and the need of long-term drug delivery. To solve the problem, the CNTF can be encapsulated in a semi-permeable membrane to form a microcapsule, which may then achieve the release of bioactive substances encapsulated, or bioactive molecules secreted by living cels and smal molecular metabolites through semi-permeability of the special membrane. OBJECTIVE:To prepare a special structural CNTF sustained-release microcapsule. METHODS: A selected poly(ether sulfone) holow fiber was cut into 1 cm long with its two ends sealed by 1181-M medical adhesive using UV curing. To prepare CNTF encapsulated microcapsule, one end was first sealed, and then the CNTF was loaded to poly(ether sulfone) microcapsule from the other end which then was sealed. The leaching liquor of sustained-release microcapsule was co-cultured with mouse fibroblast L929, to observe the cytotoxicity of the microcapsule. The sustained-release microcapsule was co-cultured with mouse retinal pigment epithelial cels, to observe the celladhesion ability of the microcapsule. The CNTF sustained-release microcapsule was immersed in physiological saline, to observe the degradability. Moreover,in vitro release behavior of immunoglobulin and CNTF were evaluated. RESULTS AND CONCLSIONThe CNTF sustained-release microcapsule had an inner diameter of about 398 μm and a membrane thickness of about 145 μm. The microcapsule presents a lot of macropores in the outer wal and many 10 nanometers micropores in the inner wal. The sustained-release microcapsule was not degraded in saline within 4 months, indicating good cellcompatibility. The microcapsule can selectively release CNTF while protecting against invading of antibodies (IgG), showing its good selective permeability. Meanwhile, the sustained-release microcapsule improved the initial burst release of traditional drug delivery vesicles. The microcapsule presents a mild sudden release in the middle stage, and then a sustained release.