The present invention relates to biocompatible polymeric beads and to biocompatible delivery systems comprising same for controlled or sustained release of bioactive mols. In particular, the invention relates to polymeric beads having a two-phase core and shell structure and to polymeric delivery systems comprising same that provide sustained release of the bioactive compd. A method of prepg. the biocompatible polymeric beads, comprises: (1) mixing an aq. soln. or suspension of the bioactive compd. in an oily phase to form a water-in-oil emulsion, in the presence of at least one surface active agent; (2) homogenizing the mixt.; (3) applying a polymeric shell around small droplets of the emulsion by means of core/shell extrusion; and (4) solidifying the shell to form two phase core-and-shell-structured polymeric beads. For example, both emulsion and suspension bead expts. were conducted with micronized halofuginone·HBr (I). A water-in-oil emulsion was prepd., in which the internal phase contained I and the oil was sunflower oil. Beads were formed by a core-shell double nozzle using a shell soln. contg. Na alginate and a crosslinking agent contg. CaCl2. [on SciFinder(R)]

The present invention relates to biocompatible polymeric delivery systems for controlled or sustained release of quinazolinone derivs.(I; n = 1-2; R1 = H, halo, NO2, benzo, alkyl, Ph, alkoxy; R2 = OH, acetoxy, alkoxy; R3 = H, alkenoxy carbonyl), including the compd. halofuginone. In particular the invention relates to a polymeric delivery system comprising biocompatible polymeric beads having a two-phase core and shell structure, or polymeric films, beads or complexes that provide local sustained release of the pharmacol. agent. For example, polymeric emulsion beads with core/shell structure were prepd. for controlled release of halofuginone. A water-in-oil emulsion was prepd., in which the 20% wt. internal phase contained 50 mg halofuginone HBr/mL and the oil was sunflower oil. The emulsion was prepd. by adding the aq. halofuginone soln. in to the oil which contains 2.7% wt. span 80, and homogenized. Beads were formed by a core-shell double nozzle Innotek. The shell soln. was 2.5% sodium alginate and 2.5% silica in aq. soln. [on SciFinder(R)]

In vitro compartmentalization (IVC) uses water-in-oil emulsions to create artificial cell-like compartments in which genes can be individually transcribed and translated. Here, we present a new application of IVC for the selection of DNA-nuclease inhibitors. We developed a nano-droplets delivery system that allows the transport of various solutes, including metal ions, into the emulsion droplets. This transport mechanism was used to regulate the activity of colicin nucleases that were co-compartmentalized with the genes, so that the nucleases were activated by nickel or cobalt ions only after the potential inhibitor genes have been translated. Thus, genes encoding nuclease inhibitors survived the digestion and were subsequently amplified and isolated. Selection is therefore directly for inhibition, and not for binding of the nuclease. The stringency of selection can be easily modulated to give high enrichments (100-500-fold) and recoveries. We demonstrated its utility by selecting libraries of the gene encoding the cognate inhibitor of colicin E9 (immunity protein 9, or Im9) for inhibition of another colicin (ColE7). The in vitro evolved inhibitors show significant inhibition of ColE7 both in vitro and in vivo. These Im9 variants carry mutations into residues that det. the selectivity of the natural counterpart (Im7) while completely retaining the residues that are conserved throughout the family of immunity protein inhibitors. The in vitro evolution process confirms earlier hypotheses regarding the "dual recognition" binding mechanism and the way in which new colicin-immunity pairs diverged from existing ones. [on SciFinder(R)]

{The present invention provides a drug delivery system comprising nanoparticles or microparticles of a water poorly sol. drug dispersed in a polymeric bead contg. essentially only of hydrophilic polymers (i.e., without hydrophobic polymers). The present invention further provides a method of producing the drug delivery system of the invention. Thus, a 4% sodium alginate soln. was prepd. by mixing 16 g of sodium alginate and 400 g water together with 0.4 g of Bronopol (preservative) at about 37° until complete dissoln. A crosslinking agent was prepd. by dissolving 14.8 g of calcium chloride dihydrate in 1000 g water. An oil-in-water emulsion (20% oil phase, 80% aq. phase) was prepd. contg. 3% surfactant (mixt. of Tween 20 and Span 20

The interaction between the anionic surfactant, Na dodecyl sulfate, and the polyelectrolyte, poly(diallyldimethylammonium chloride), may give nanoparticles dispersed in H2O. The morphol. of the resulting nanoparticles and their ability to solubilize hydrophobic mols. were evaluated. As shown by SEM and AFM imaging, the particles are spherical, having a diam. of \~20 nm. The solubilization within the nanoparticles was tested with pyrene, a fluorescence probe, and Nile Red, a solvatochromic probe. For Nile Red the solubilization within the nanoparticles is at lower polarity than for SDS micelles, and from pyrene solubilization apparently the hydrophobicity of the nanoparticles depends on the ratio between the SDS mols. and the charge unit of the polymer. [on SciFinder(R)]