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Targeted Administration of Proteic Drugs. I. Preparation of Polymeric Nanoparticles

Elisabetta E. Chiellini

Federica Chiellini

Roberto Solaro

Department of Chemistry and Industrial Chemistry, University of Pisa, via Risorgimento 35, 56126 Pisa, Italy

The formulation of hybrid nanoparticles based on synthetic polymer-protein hybrid matrices for the targeted release of proteic drugs with antiviral activity such as a-interferon was investigated. Human serum albumin, alone, or in combination with myoglobin, and the hemiesters of alternating copolymers of maleic anhydride/alkyl vinyl ethers of oligo(ethylene glycol) were selected as proteic and synthetic components, respectively. Digalactosyl diacyl gycerol, a natural glycolipid selectively recognized by the asialofetuin receptor was used for the active targeting of liver hepatocytes. Nanoparticle suspensions were prepared either by slow solvent evaporation from biphase and triphase emulsions or by controlled coprecipitation. Nanoparticles, 0.1-0.3 gm in diameter, were obtained by the latter method, whereas the former one afforded heterogeneous micro and nanoparticle mixtures. Several techniques were tested to separate the nanoparticle dispersions from the suspending solution. The best results, in terms of a homogeneous distribution of mostly spherical nanoparticles, were obtained by centrifugation in the presence of modified cyclodextrins. After lyophilization of supernatant, the resulting fluffy powder was easily resuspendable in water.

Journal of Bioactive and Compatible Polymers, Vol. 16, No. 6, 441-465 (2001)
DOI: 10.1106/6CFL-4E8A-L7XR-MUF7


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