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POLYMERIC SURFACTANT MICELLES AS MICROCONTAINERS FOR NEUROLEPTIC TARGETING IN THE BRAIN Alexander V. Kabanov, Vlad imi r P. Chekhonin* All-Union Research Centre of Molecular Diagnostics and Therapy, Simpheropolsky blvd. 8, Moscow 113149 and *All- Union Research Institute for General and Foreraic Psychiatry, Kropotkinskii per. 23, Moscow 119839, USSR Microcontainers for drug targeting were prepared using polymeric suffactant pluronic (poly(oxyethylene)-poly(oxypropylene) block eopolymer) t. Molecules of a drug are solubilized in a pluronic micelle being incorporated into its inner hydrophobic core, formed by poly(oxypropylene) chain blocks. Outer hydrophylic shell of such micelle is formed by nontoxic and nonimmunogenic poly(oxyethylene) blocks. According to quasielastic light scattering data the diameter of pluronic micelles (including these containing solubilized compounds) was in the range of 14 - 20 nm. For targeting of such microcontainers to a certain cell pluronic molecules were conjttgated with antibodies against a target-specif:,'- antigen. The obtained conjugates were incorporated into the drug containing micelles by mixing of the corresponding components. Interaction of the miceUar microcontainer with a cell in vitro results in penetration of solubilized low molecular weight compounds incorporated in the hydrophobic core as well as a protein conjugated with the micelle forming surfactani into a cell. Solubilization of FITC in pluronic mi.celles considerably influence distribution of this compouad in mouse tissues after parenteral administration. FITC containing miceUes modified by antibodies against neurospecific antigen (or 2- glycoprotein), are targeted to brain. Possibility of using of micellar microcontainers for targeting of solubilized neuroleptic (haloperidol) in brain was demonstrated I. Solubilization of haloperidol in pluronic micelles results in change of dynamics of haloperidoi action and in 1.5-5 folk increase of its specific neuroleptic activity. Incorporation of antibodies into haloperidol containing micelles results in additional drastic increase (more than by 2 orders of magnitude) of the drug effect 1. Kabanov, A.V. et al., (1989) FEBS Left., 258, 343-345.

CLONING OF MICROGLIAL CELLS FROM PROGENITORS IN THE BRAINS OF NEWBORN AND ADULT MICE Elvia Armendar iz , Jane t Gatewood, Twala L. Hogg, Jeffrey M. McCormack , Steven C. Moore, Deming Sun, and Wil l iam S. W a l k e r Dept. of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38101, USA We report the successful soft-agar cloning of microglial cells from progenitors in the brains of normal newborn and adult mice. Cells from nylon wool-filtrates of trypsin-DNAase digested meninges-free brains were suspended in warmed Dulbecco's modified Eagle medium (DMEM) containing 0.3% melted agar and this mixture was plated over a hardened base of 0.5% agar in DMEM. The DMEM was supplemented with 20% pre- screened fetal bovine serum and 10% conditioned medium (CM) from ceil lines that secrete different growth factors. As found in a previous study with mouse splenic macrophage progenitom (Cell. Immunol. 107:417, 1987), by day 14 of culture, only CM from the LADMAC cell line, which secretes the macrophage-specific growth factor colony stimulating factor- 1 (CSF- 1) (J.Cell.Physiol. 125:403, 1985) promoted maximum macroscopic colony formation (ca. 320110,000 cells plated). The CM from mouse and rat astrocyte cell lines and WEHI-3 were at least 5-fold less effective and mixing of the various CM indicated that CSF-I was likely the only required grewth factor. The CSF-1 dependency and the preliminary results of functional, immunopbenotypie and molecular analyses are consistent with most of the colonies being members of the macrophage family of cells. (Supported by NIH grants AI 17979, CA 21764 and by ALSAC.)