Mechanisms involved in the formation of biocompatible lipid polymeric patchy particles

Abstract

The invention relates to lipid polymeric patchy particles formed by nanoprecipitation and emulsification processes, utilizing a polymer blend including the polymer, solvent and lipid-PEGylated functional groups. More particularly, the invention relates to synthesizing particles having different or pre-selected morphologies (internal and external) and physicochemical properties. It has been found that the shear stress experienced by the polymer blend during emulsification can impart certain external and internal morphology and physicochemical properties to the resulting particles. Further, the one or more patches of the particles can be functionalized, such as, with gold nanoparticles, for use of the particles, in particular, in photoacoustic and ultrasound imaging.

1 - 18 . (canceled) 
     
     
         19 . A lipid polymeric patchy particle comprising:
 (a) a solid core having an outer surface surrounding the solid core;   (b) one or more shells surrounding the outer surface;   (c) a plurality of patches formed on the outermost shell; and   (d) a first lipid functional group having a first end and a second end, wherein the first end is bound to the outer surface, thereby forming a first shell, and wherein the second end has a first functional group,   wherein the outer surface comprises a hydrophobic polymer.   
     
     
         20 . The particle of  claim 19 , wherein the particle further comprises a second lipid functional group having a first end and a second end,
 wherein the first end of the second lipid functional group is bound to the outer surface, thereby forming the first shell, together with the first lipid functional group, and   wherein the second end of the second lipid functional group has a second functional group, wherein the first lipid functional group and the second lipid functional group are different.   
     
     
         21 . The particle of  claim 19 , wherein the hydrophobic polymer is a biocompatible, biodegradable polymer. 
     
     
         22 . The particle of  claim 19 , wherein the hydrophobic polymer is poly(lactide-co-glycolide) polymer. 
     
     
         23 . The particle of  claim 19 , wherein the first lipid functional group is a lipid-PEGylated functional group. 
     
     
         24 . The particle of  claim 23 , wherein the first lipid functional group has a formula: -1,2-distearoyl-sn-glycerol-3-phosphoethanolamine (DSPE)-N-poly(ethylene glycol) (PEG)-R, wherein R is a functional group. 
     
     
         25 . The particle of  claim 23 , wherein the first lipid functional group has a formula: -DSPE-PEG-R, wherein R is selected from amino, methoxyl, and maleimide (MAL). 
     
     
         26 . The particle of  claim 19 , wherein the particle comprises the first shell and a second shell, wherein the second shell surrounds the first shell. 
     
     
         27 . The particle of  claim 26 , wherein the particle further comprises a second lipid functional group having a first end and a second end,
 wherein the first end of the second lipid functional group is bound to the second shell, and   wherein the second end of the second lipid functional group has a second functional group, wherein the first lipid functional group and the second lipid functional group are different.   
     
     
         28 . The particle of  claim 27 , wherein the second lipid functional group has a formula -DSPE-PEG-NH 2  and wherein the different lipid functional group has a formula -DSPE-PEG-MAL. 
     
     
         29 . The particle of  claim 19 , wherein bound is via covalent bonds. 
     
     
         30 . The particle of  claim 19 , wherein a semi-conductor polymer is embedded in the solid core. 
     
     
         31 . The particle of  claim 30 , wherein the semi-conductor polymer is poly [2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b, 3, 4-alt-4,7(2, 1, 3-benzothiadiazole)] (PCPDTBT). 
     
     
         32 . The particle of  claim 19 , wherein a payload is embedded in the solid core. 
     
     
         33 . A method of making a lipid polymeric patchy particle, wherein the method comprises:
 (a) combining:
 (i) a first solution comprising a lipid-PEGylated functional group; and 
 (ii) a second solution comprising a hydrophobic polymer, 
 thereby forming a polymer blend; 
   (b) emulsifying the polymer blend using a high shear mixer assembly, thereby forming an emulsified blend,   wherein the particle comprises a hollow core and a single patch or wherein the particle comprises a solid core and a plurality of patches.   
     
     
         34 . The method of  claim 33 , wherein the method further comprises adjusting the magnitude of shear stress, thereby controlling the particle's external and internal morphology. 
     
     
         35 . The method of  claim 34 , wherein a high shear stress is applied and wherein the particle comprises the hollow core and the single patch. 
     
     
         36 . The method of  claim 34 , wherein a low shear stress is applied and wherein the particle comprises the solid core and the plurality of patches. 
     
     
         37 . The method of  claim 33 , wherein the high shear mixer assembly comprises:
 (a) a homogenizer workhead having an inner diameter; and   (b) a rotor shaft having an outer edge,   wherein the magnitude of shear stress is controlled by the distance between the inner diameter of the homogenizer workhead and the outer edge of the rotor shaft.   
     
     
         38 . The method of  claim 33 , wherein the distance between the inner diameter of the homogenizer workhead and the outer edge of the rotor shaft is in the order of micrometers.