Mineral coated microparticles for gene delivery in chronic wound therapy
AssigneeWisconsin Alumni Research Foundation
InventorsWilliam L. Murphy, Andrew Salim Khalil, Xiaohua Yu
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Abstract
Disclosed are formulations for providing a therapeutic bioactive polypeptide to injured tissue. Formulations include mineral coated microparticles wherein a polynucleotide is adsorbed to the mineral layer. Other formulations include a carrier including mineral coated microparticles wherein mineral coated microparticles include a polynucleotide. Also disclosed are methods for sustained delivery of a bioactive polypeptide and methods for treating chronic wounds using a formulation for providing sustained delivery of the bioactive peptide.
Claims10
A method of repairing injured tissue in a subject in need thereof, the method comprising:
- contacting a microparticle comprising a mineral layer with a polynucleotide selected from the group consisting of small interfering RNAs (siRNAs), messenger RNA (mRNA), short hairpin RNAs (shRNAs), and RNA aptamers, wherein the polynucleotide is adsorbed to the mineral layer;
- and
- contacting the microparticle with the injured tissue, wherein the polynucleotide is released, is taken up by cells of the injured tissue, and results in increased production of a bioactive peptide, wherein the bioactive polypeptide is selected from the group consisting of cytokines, growth factors, and combinations thereof;
- wherein the bioactive polypeptide secreted from the cells becomes sequestered with the microparticle, and subsequently is released as the mineral layer of the mineral coated microparticle degrades,
- wherein the injured tissue is a diabetic ulcer, and
- wherein the mineral layer is in the shape of a needle having an average length of from about 10 nm to about 750 nm.
A method for sustained delivery of bioactive polypeptides, the method comprising:
- contacting a mineral coated microparticle comprising a mineral layer with a polynucleotide adsorbed thereto with at least one cell, wherein the mineral layer comprises calcium, phosphate, carbonate and combinations thereof, and wherein the polynucleotide encodes a bioactive polypeptide selected from the group consisting of cytokines, growth factors, and combinations thereof, wherein the polynucleotide is released, is taken up by the at least one cell of the injured tissue, and results in increased production of the bioactive peptide in the at least one cell;
- wherein the bioactive polypeptide secreted from the cells becomes sequestered with the microparticle via electrostatic interactions between the polypeptide and the microparticle, and subsequently is released as the mineral layer of the mineral coated microparticle degrades, wherein the injured tissue is a diabetic ulcer, and
- wherein the mineral layer is in the shape of a needle having an average length of from about 10 nm to about 750 nm.
Dependencies are inferred from the claim text.