Nano-Particulate Design and Preparation for Targeting and Controled Release of Drugs

Nano-particulate systems have attracted much attention recently in pharmaceutical field as drug carriers and functional components of pharmaceutical dosage forms. This paper describes our approaches in design and preparation of nano-particulate systems, including lipid nano-emulsions, chitosan nanoparticles and thermosensitive acrylic nanoparticles, for certain pharmaceutical applications mentioned below. The lipid nano-emulsions with their particle size smaller than 100 nm were prepared for gadolinium neutron-capture therapy (Gd-NCT) of cancer by a thin-film hydration method with sonication, and intraperitoneally injected into Greene's melanoma (melanotic No. 179)-bearing Syrian hamsters. This provided such a high gadolinium concentraton in tumor as 107 µg/g tumor (wet basis) at 48 h after administration. As an alternative gadolinium nano-carrier for Gd-NCT, biodegradable and highly gadopentetate-loaded chitosan nanoparticles (Gd-nanoCPs, 426 mTI in particle diameter and 9.3% in Gd content) were prepared by a novel emulsion-droplet coalescence technique. A significant tumor-killing effect could be obtained when Gd-nanoCP suspension was injected intratumorally twice 24 and 8 hours before neutron irradiation into B 16Fl O melanoma-bearing mice and subsequently thermalneutron was irradiated toward tumor site with a flux of 2 x 109 n/cm2/sec for 60 min. As one another application of nanoparticles, a novel acrylic composite latex with a hydrophobic core and a thermosenstively swellable shell was designed for fabricating microcapsules showing thermosensitive mode of drug release. The microcapsules with the composite latex-dispersing membranes exhibited an exceptionally rapid on-off response of drug-release in a thermosensitive manner.