Delivery of large molecular weight biologically active substances

Abstract

The invention relates generally to intradermal, transdermal, and/or transmembrane delivery of biologically active substances in the epidermis and/or through the skin, sub-dermal tissues, blood vessels and cellular membranes without causing damage to the cellular surface, tissue or membrane. The biologically active substances may have a molecular weight no less than about 5.8 kDa to about 2,500 kDa, such as Hyaluronic Acid (HA). The biologically active substances may be deposited in a dermal patch containing a red algae polysaccharide-based matrix, wherein the red algae poly-saccharide is an extract of Chondrus crispus at 2% by weight of the dermal patch. The invention provides systems and methods for enhanced intradermal, transdermal, and/or transmembrane delivery of such biologically active substances using pulsed incoherent light. The invention further provides a device for the application of the pulsed incoherent light to cellular surfaces and membranes using those compositions and methods.

1 . A device for photokinetic intradermal and/or transdermal delivery of a biologically active substance to a subject, said device comprising:
 (1) a generator that provides an oscillating electrical pulse;   (2) at least one light emitting diode that receives the oscillating electrical pulse and responds by providing an incoherent light; and,   (3) a donor cell that holds a formulation comprising the biologically active substance, wherein the donor cell is positioned to receive the incoherent light.   
     
     
         2 - 54 . (canceled) 
     
     
         55 . A method for photokinetic intradermal and/or trans dermal delivery of a biologically active substance having a molecular weight of no less than 5800 Da to a subject, the method comprising:
 (1) preparing a formulation comprising the biologically active substance;   (2) applying said formulation to a cellular surface on the skin of the subject;   ( 3 ) illuminating said formulation on said cellular surface with a pulsed incoherent light having a selected wavelength, pulse rate and duty cycle; and,   (4) allowing said biologically active substance in said formulation to permeate said cellular surface, thereby effecting photokinetic intradermal and/or transdermal delivery of the biologically active substance.   
     
     
         56 - 61 . (canceled) 
     
     
         62 . The method of  claim 55 , wherein the formulation comprises a gelling agent. 
     
     
         63 . (canceled) 
     
     
         64 . The method of  claim 55 , wherein the formulation further comprises a photocatalytic agent. 
     
     
         65 - 72 . (canceled) 
     
     
         73 . The method of  claim 55 , wherein said biologically active substance comprises sodium hyaluronate (e.g., one with a M.W. of at least about 1000 kDa, 1600 kDa, 2200 kDa, 2500 kDa, 3000 kDa, 3500 kDa, 4000 kDa, 4500 kDa, 5000 kDa). 
     
     
         74 . The method of  claim 55 , wherein said biologically active substance is a cosmetic agent, or a therapeutic agent. 
     
     
         75 . The method of  claim 55 , wherein said biologically active substance comprises:
 (1) a peptide selected from the group consisting of Gly-Tyr, Val-TyrVal, Tyr-Gly-Gly-Phe-Met (SEQ ID NO: 1), Tyr-Gly-Gly-Phe-Leu (SEQ ID NO: 2), and Asp-Arg-Val-Tyr-Ile-His-Pro-Phe (SEQ ID NO: 3);   (2) a hormone selected from the group consisting of methionine enkephalin acetate, leucine enkephalin, angiotensin II acetate, f)-estradiol, methyl testosterone, and progesterone; or,   (3) a protein selected from the group consisting of enzymes, nonenzymes, antibodies, and glycoproteins.   
     
     
         76 . (canceled) 
     
     
         77 . The method of  claim 55 , wherein said pulsed incoherent light is selected from the group consisting of fluorescent, ultraviolet, visible, near infrared, LED (light emitting diode), and halogen light. 
     
     
         78 - 83 . (canceled) 
     
     
         84 . The method of  claim 55 , wherein said pulse rate is between about 1.7 cycles per second (cps) and about 120 cps, or about 1.7 cps and about 80 cps. 
     
     
         85 . (canceled) 
     
     
         86 . The method of  claim 55 , wherein said duty cycle is between about 50% and about 75%. 
     
     
         87 . The method of  claim 55 , further comprising adjusting the transdermal flux rate of the biologically active substance by modulating the light energy. 
     
     
         88 - 110 . (canceled)