Targeted delivery methods and compositions for antihistamines

Abstract

Products, compositions, and methods for using one or more small particles to facilitate the delivery of one or more antihistamines to a human body are disclosed. In some aspects, methods are disclosed that utilize small particles that may be integrated with one or more guiding antibodies that detect and bind to high affinity immunoglobulin E receptors associated with various types of target cells, such as mast cells, basophils, and dendritic cells. Methods in accordance with the present disclosure may use small particles that are configured to contain relatively high concentrations of at least one form of at least one antihistamine and deliver the antihistamine(s) to areas within a human body where one or more actions associated with an allergic reaction may be in progress and/or where one or more actions associated with an allergic reaction may be likely to occur.

What is claimed is: 
     
         1 . A composition comprising
 a nanoparticle having an FcεR targeting moiety extending from an external surface of the nanoparticle, and   an antihistamine contained in the nanoparticle.   
     
     
         2 . The composition of  claim 1 , wherein the antihistamine is selected from the group consisting of azelastine, carbinoxamine, cyproheptadine, desloratadine, emedastine, hydroxyzine, levocabastine, levocabastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, diphenhydramine, fexofenadine, loratadine, and combinations thereof. 
     
     
         3 . The composition of  claim 1 , wherein the nanoparticle is a liposome. 
     
     
         4 . The composition of  claim 1 , wherein the targeting moiety is selected from a peptide, a small molecule, and an antibody. 
     
     
         5 . The composition of  claim 4 , wherein the targeting moiety is a monoclonal antibody that has a dissociation constant selected from 8.15×10 −8 , 4.21×10 −8 , 4.75×10 −8 , 1.88×10 −7 , and 8.53×10 −8  molar as measured by an Octet® RED96 instrument. 
     
     
         6 . The composition of  claim 1 , wherein the FcεR targeting moiety is an FcεRI targeting moiety. 
     
     
         7 . A formulation comprising the composition of  claim 1  formulated for low-dose delivery of antihistamine. 
     
     
         8 . The formulation of  claim 7 , wherein the antihistamine is selected from the group consisting of azelastine, carbinoxamine, cyproheptadine, desloratadine, emedastine, hydroxyzine, levocabastine, levocabastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, diphenhydramine, fexofenadine, loratadine, and combinations thereof. 
     
     
         9 . The formulation of  claim 7 , wherein the nanoparticle is a liposome. 
     
     
         10 . The formulation of  claim 9 , wherein at least one type of antihistamine is in an aqueous core of the liposome and at least a second type of antihistamine is in a lipid bilayer of the liposome. 
     
     
         11 . The formulation of  claim 7  further comprising a second composition of  claim 1 , wherein the nanoparticle of the second composition is configured for an extended release. 
     
     
         12 . The formulation of  claim 7  formulated for aerosol delivery. 
     
     
         13 . A method for treating allergic reactions comprising
 obtaining a composition comprising a nanoparticle having an FcεR targeting moiety extending from an external surface of the nanoparticle, and an antihistamine contained in the nanoparticle; and   delivering the composition to an FcεR in a patient.   
     
     
         14 . The method of  claim 13  further comprising delivering the antihistamine to a histamine receptor in the patient. 
     
     
         15 . The method of  claim 13 , wherein the composition comprises a second type of antihistamine in the nanoparticle. 
     
     
         16 . The method of  claim 13 , wherein the targeting moiety is selected from a peptide, a small molecule, and an antibody. 
     
     
         17 . The method of  claim 16 , wherein the targeting moiety is a monoclonal antibody, the method further comprising binding of the monoclonal antibody to the FcεR to prevent or minimize cross-linking of IgE and release of mediators. 
     
     
         18 . The method of  claim 13 , wherein the antihistamine is selected from the group consisting of azelastine, carbinoxamine, cyproheptadine, desloratadine, emedastine, hydroxyzine, levocabastine, levocabastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, diphenhydramine, fexofenadine, loratadine, and combinations thereof. 
     
     
         19 . The method of  claim 13 , wherein the nanoparticle is a liposome. 
     
     
         20 . The method of  claim 13 , wherein the FcεR is on a target cell selected from the group consisting of a mast cell, a basophil, and a dendritic cell. 
     
     
         21 . The method of  claim 13  formulated for low-dose delivery of antihistamine. 
     
     
         22 . The method of  claim 21  further comprising administering the formulation to a patient. 
     
     
         23 . The method of  claim 22  further comprising delivering the antihistamine to a histamine receptor in the patient. 
     
     
         24 . The method of  claim 22  further comprising administering the formulation to the patient a second time after at least two days. 
     
     
         25 . The method of  claim 22 , wherein the at least one antihistamine is selected from the group consisting of azelastine, carbinoxamine, cyproheptadine, desloratadine, emedastine, hydroxyzine, levocabastine, levocabastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, diphenhydramine, fexofenadine, loratadine, and combinations thereof. 
     
     
         26 . The method of  claim 22 , wherein the nanoparticle is a liposome. 
     
     
         27 . The method of  claim 22  further comprising binding of the antibody to an FcεRI on a target cell to prevent or minimize cross-linking of IgE and release of mediators. 
     
     
         28 . The method of  claim 27 , wherein the target cell is selected from the group consisting of a mast cell, a basophil, and a dendritic cell. 
     
     
         29 . The method of  claim 22  further comprising delivery of the formulation to portions of a respiratory system of the patient. 
     
     
         30 . The method of  claim 22  further comprising delivery of the formulation to portions of a systemic circulation of the patient.