Lecithin/PLGA Composite Microspheres for Sustained Release Delivery of Hydrophilic Protein

来源 :第二届全国生物颗粒学术研讨会、第三届国际工业药学和临床药学研讨会暨第一届岭南国际药学大会 | 被引量 : 0次 | 上传用户:lsy999
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  There was a conventional water-in-oil-in-water (W/O/W) double emulsion technique that had been widely used to prepare PLGA microspheres due to its simplicity of the fabrication processes.However, this method generally resulted in high burst release from microspheres at the initial stage because hydrophilic peptide was easy to diffuse to the external water phase during the preparation processes and distributed at the surface of microspheres.The purpose of this work was to develop a novel composite lecithin/poly (lactic-co-glycolic) acid (PLGA) microparticulate system with low burst release effect and this delivery system was purposed to attained sustain-release for hydrophilic peptide.A modified method, which called solid-in-oil-in-water (S/O/W), was used in this study.And our previous study demonstrated that this method could decrease the initial burst release and maintain the bioactivity of peptide.Bovine Serum Albumin (BSA), the extremely soluble model protein dissolving in water with lyoprotectant, was mixed with tert-butanol containing lecithin to form lipid vesicles, followed by a freeze-drying process to remove solvents.Then the lyophilized lecithin nanoparticles loaded peptide, which gained resistance to organic solvents or water-air interfaces and cross-linking reagents, was encapsulated into PLGA microspheres by the solvent diffusion evaporation technique.Characteristics of composite microspheres including morphology, particle size distribution, entrapment efficiency, loading content and in vitro release were investigated.The lecithin/PLGA composite microsphere showed a spherical shape, smooth surfaces and diameters ranging from 2 to 5 μm.Invitro release study indicated peptide drug released from microspheres in a long-effective manner and lasted up to 50 days with low burst release (≈10% at the first day).Moreover, the bio-stability of Bovine Serum Albumin was confirmed to be preserved during the preparation process by circular dichroism (CD) spectrum analysis.The lecithin/PLGA composite microspheres could be a potential platform for peptide stabilization and sustain-release delivery.
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