Solid lipid nanoparticle for intracellular release of active substances and method for production the same

Abstract

The invention relates to solid lipid nanoparticle for intracellular release of active substances, can be used in the pharmaceutical industry, in the medicine, cosmetics, as well as for food supplements. Solid lipid nanoparticle has spherical shape with a diameter of 15-100 nm, the lipid is a solid lipid selected from natural plant wax or its synthetic analogue, as the surface acting agent is used TMDSC. The particles of solid lipid nanoparticle is characterized with high melting point, high lipophilicity and low (or lack) of in-vitro dissolution profile. The system is lipase-resistant and is capable to freely penetrate through cell membranes into cells where to release the active substance(s) due to an intracellular digestion with controllable depo-effect. In a second aspect, the invention relates to a method of production of the solid lipid nanoparticle. The preferred technology for production of the compositions is a Phase Inversion Temperature method.

1 . Solid lipid nanoparticle for intracellular release of active substances containing a lipid, a surface acting agent, water and an active compound, characterized by that, the solid lipid nanoparticle is with spherical shape with a diameter of 15-100 nm, the lipid is a solid lipid selected from natural plant or synthetic wax, as the surface acting agent is used d-α-Tocopheryl polyethylene glycol 1000 succinate, the active substance is incorporated in the nanoparticles and the components of the solid lipid nanoparticles are in the following quantitative ratios in w/w parts: from 0.01 to 20 parts natural plant wax or its synthetic analogue, from 0.01 to 20 parts d-α-Tocopheryl polyethylene glycol 1000 succinate, an active substance from 0.00001 to 10 parts and water in the amount up to 100 parts. 
     
     
         2 . Solid lipid nanoparticle for intracellular release of active substances according to  claim 1 , wherein the natural plant wax is carnauba wax. 
     
     
         3 . Solid lipid nanoparticle for intracellular release of active substances according to  claim 1 , which further comprises a liquid lipid in an amount up to 20% of the total lipid. 
     
     
         4 . Solid lipid nanoparticle for intracellular release of active substances according to  claim 3 , wherein the liquid lipid is selected from the group consisting of natural or synthetic oil with high content of Tocotrienol, such as red palm oil, rice bran oil, wheat germ oil or animal oils. 
     
     
         5 . Solid lipid nanoparticle for intracellular release of active substances according to  claim 3 , wherein the liquid lipid is mono- or mix from isomers of Tocotrienol. 
     
     
         6 . Solid lipid nanoparticle for intracellular release of active substances according to  claim 1 , wherein the surface acting agent further comprises a polysorbate, such as polysorbate 20, polysorbate 40, polysorbate 60 or polysorbate 80, preferably from 0.01 to 10 w/w parts. 
     
     
         7 . Solid lipid nanoparticle for intracellular release of active substances according to  claim 6 , wherein the polysorbate is polysorbate 40. 
     
     
         8 . Solid lipid nanoparticle for intracellular release of active substances according to  claim 1 , wherein the active substance is drug substances, diagnostic agents, biological products, food supplements, cosmetic products or medical devices. 
     
     
         9 . Method of production of solid lipid nanoparticle, according to  claim 1 , characterized by that, the lipid compound/compounds, the surface acting agent/agents and an active substance are heated up to 90°±2° C. to melt under stirred until a homogeneous clear mixture is obtained, to the mixture obtained is added drop wise under stirring the water, heated in advance to the same temperature and after that the dispersion obtained is cooled down gradually under stirring to 20°±2° C. to give the nanoparticle dispersion.