Resumen
[0001] The present invention in particular relates to the field of micro- and nanoparticles, more in particular to coated nanoparticles. The coatings of the present invention in particular comprise surfactant protein B (SP-B) and one or more lipids. The invention further relates to such coated particles and compositions comprising them for use as a medicament, in particular for use in the treatment of various disorders. Furthermore, the invention provides the use of the compositions of the current invention for delivering one or more agents, such as small interfacing RNA (siRNA) molecules, to the target tissue or cells.
Reivindicaciones
CLAIMS 1 . An intracellular drug delivery composition comprising a particle, said particle comprising one or more active agents and a proteolipid composition, said proteolipid composition consisting of (a) surfactant-protein B (SP-B) and (b) one or more lipids; wherein said particle is not a cationic liposome; and wherein said drug delivery composition does not comprise SP-C. 2. The composition according to claim 1 , wherein the one or more lipids are phospholipids. 3. The composition according to claim 1 or 2, wherein said phospholipids are selected from the list comprising: 1 ,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1 -palmitoyl-2- oleoyl-sn-glycero-3-phosphocholine (POPC), 1 -stearoyl-2-oleoyl-sn-glycero-3- phosphocholine (SOPC), 1 ,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1 ,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1 ,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), 1 ,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1 ,2- dilauroyl-sn-glycero-3-phosphocholine (DLPC), L-a-phosphatidylcholine ((egg)PC), L-a- phosphoethanolamine ((egg)PE), 1 ,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG), L-a-phosphatidylglycerol ((egg)PG), 1 ,2-dioleoyl-sn-glycero-3-phosphatidic acid (DOPA), L-a-phosphatidic acid ((egg)PA), or combinations thereof. 4. The composition according to claim 2 or 3, wherein the phospholipids are a combination of one or more zwitterionic phospholipids and one or more anionic phospholipids. 5. The composition according to claim 3 or 4, wherein said phospholipids are a combination of DPPC:(egg)PG (1 ,2-dipalmitoyl-sn-glycero-3-phosphocholine; L-a- phosphatidylglycerol), a combination of DPPC:(egg)PA (1 ,2-dipalmitoyl-sn-glycero-3- phosphocholine; L-a-phosphatidic acid), a combination of DOPC:(egg)PG (1 ,2-dioleoyl-sn- glycero-3-phosphocholine; L-a-phosphatidylglycerol) or a combination of DOPC:(egg)PA (1 ,2-dioleoyl-sn-glycero-3-phosphocholine; L-a-phosphatidic acid). 6. The composition according to claim 5, wherein said DPPC:(egg)PG, DPPC:(egg)PA, DOPC:(egg)PG or DOPC:(egg)PA has a ratio of about 85:15. 7. The composition according to any one of claims 1 -6, wherein said SP-B, or said SP-B related protein or peptide, is present at a weight ratio of about 0,1 wt% to about 5,0 wt% with respect to the complete proteolipid composition; more specifically between about 0,4 wt% and about 1 ,6 wt%. 8. The composition according to any one of claims 1 -7, wherein the particle is a dextran nanogel, more in particular a cationic dextran nanogel. 9. The composition according to any one of claims 1 -8, wherein the one or more active agents are selected from the list comprising: a therapeutic agent, a biologically active agent or a diagnostic imaging agent. 10. The composition according to claim 9, wherein the active agent is a nucleic acid, in particular siRNA. 1 1 . The composition according to any one of claims 1 -10, wherein the particle further comprises a targeting ligand, an imaging agent, a fluorescent agent, a PEGylated lipid or a functionalized lipid. 12. A pharmaceutical composition comprising the composition according to any one of claims 1 -1 1 , and a pharmaceutically acceptable excipient, carrier and/or diluent. 13. The composition according to any one of claims 1 -12, for use as a medicament. 14. Use of the composition according to any one of claims 1 -12, for delivering the active agent(s) across cellular membranes in a subject. 15. The use according to claim 14, wherein the composition is administered to the subject by inhalation. 16. Use of a proteolipid composition consisting of surfactant protein B (SP-B) and one or more lipids, for coating particles, in particular dextran nanogels; and wherein said particle is not a cationic liposome.
