Nanoparticles for delivery of a pharmacologically active agent, comprising water insoluble (co)polymer core amp; hydrophilic acrylate-based (co)polymer shell

摘要

Core-shell nanoparticles comprisWC 1e: SL LI(a) a core which comprises a water insoluble polymer or copolymer, and LI(b) a shell which comprises a hydrophilic polymer or copolymer; /SL ```said nanoparticles being obtainable by emulsion polymerization of a mixture comprising, in an aqueous solution, at least one water-insoluble monomer (especially a styrenic, WC 1acrylic or methacrylic monomer) to form the core and either: SL LI(i) a monomer of formula (I): EMI ID=1.1 HE=15 WI=25 LX=406 LY=498 TI=CF wherein R1 represents hydrogen or methyl, and R2 represents -COOAOH, -COO-A-NR9R10 or -COO-A-N+R9R10R11 X-, in which A represents C1-20 WC 1alkylene, R9, R10 and R11 each independently represent hydrogen or C1-20WC 1 alkyl and X represents halogen, sulphate, sulphonate or perchlorate, and a water-soluble polymer of formula (II) EMI ID=1.2 HE=16 WI=40 LX=329 LY=914 TI=CF wherein R3 represents hydrogen or methyl, R4 represents hydrogen or C1-20 alkyl, and n is an integer such that the polymer of formula (II) WC 1has a number-average molecular weight of at least 1000; or LI(ii) a hydrophilic copolymer which comprises repeating units of formulae /SL (III) and (IV): EMI ID=1.3 HE=29 WI=32 LX=403 LY=1554 TI=CF PCwherein R5 and R7 each independently represent hydrogen or methyl, R6 represents hydrogen, -A-NR9R10 or -A-N+R9R10R11 X-, which A represents C1WC 1-20 alkylene, R9, R10 and R11 each independently represent hydrogen or C1-20 alkyl and X represents halogen, sulphate, sulphonate or perchlorate and R8 represents C1-10 WC 1alkyl. The shell is formed by (i) or (ii). The nanoparticles may further comprise, adsorbed at the surface of the nanoparticles, at least one pharmacologically active agent, such as a disease-associated antigen The antigen may be a deoxyribonucleic acid, ribonucleic acid, oligodeoxynucleotide, oligonucleotide or protein; a microbial antigen or a cancer-associated antigen. A preferred antigen is a human immunodeficiency virus-l (HIV-1) antigen, especially an HIV -1 Tat protein or an immunogenic fragment thereof. Such materials may be used in a method of treatment of the human or animal body by therapy (especially for preventing or treating HN infection or AIDS) or in a diagnostic method practised on the human or animal body.