Increase Therapeutic Effects of Drug Delivering Microparticles
Drug delivery systems utilizing microparticle blends that incorporate poly(propylacrylic acid) into poly(lactide-co-glycolide) improve intracellular cytosolic delivery of bioactive molecules. The therapeutic potential of bioactive molecules delivered by microparticles is reduced considerably when the microparticles accumulate in cellular lysosomal compartments without being released into the cytoplasm. Poly(propylacrylic acid) displays pH-dependent membrane disruptive functionality at endo- lysosomal pH values. However, poly(propylacrylic acid) alone cannot support a matrix that encapsulates bioactive molecules. Researchers at the University of Florida have developed micro or nano particles that incorporate poly(propylacrylic acid) into poly(lactide-co-glycolide), creating an efficient vehicle to deliver bioactive molecules. The particle will experience pH dependent disruption when inside the desired cell. These poly(propylacrylic acid) blended poly(lactide-co-glycolide) particles show enhanced cytosolic drug delivery and induce a specific immune response to the particle enclosed antigen.
Application
These poly(propylacrylic acid) poly(lactide-co-glycolide) blended particles improve efficiency of bioactive molecule delivery into eukaryotic cells
Advantages
- Poly(lactide-co-glycolide)/ poly(propylacrylic acid) blended particles are more cost effective than particles made with poly(lactide-co-glycolide) alone due to the efficient cytosolic delivery of drugs cutting down the requirement for higher drug concentrations to reach the effective therapeutic doses
- Poly(lactide-co-glycolide)is biocompatible, biodegradable, and approved by the FDA for application in humans
- Poly(propylacrylic acid) inclusion increases the amount of biomolecules released to the cytosol from endolysosomal compartments, reducing the loss of the therapeutic potential
- Poly(lactide-co-glycolide)/ poly(propylacrylic acid) particles use safe, commonly used poly(lactide-co-glycolide) as a base polymer, enabling the loading of virtually any type of bioactive molecule
- Poly(lactide-co-glycolide)/ poly(propylacrylic acid) particles are non-toxic to eukaryotic cells, limiting risks for human use
Technology
Therapeutic potential of bioactive molecules delivered by particles can be reduced considerably due to the non-availability of the therapeutic agent as a result of the accumulation of the particles containing the bioactive molecules in cellular lysosomal compartments following internalization by endocytosis or phagocytosis. To prevent this loss, the incorporation of poly(propylacrylic acid) into poly(lactide-co-glycolide) has demonstrated pH-dependent disruption and release of bioactive molecules into the cytosol, without cellular toxicity. These blended particles are biocompatible, biodegradable, and non-toxic. They are taken into the cells in the same route as pure poly(lactide-co-glycolide) particles even when poly(propylacrylic acid) is incorporated, and the particle matrix is disrupted due to the pH in the endolysosomal compartment. This allows for more efficient cytosolic delivery of antigens and therapeutic responses. These poly(lactide-co-glycolide)/ poly(propylacrylic acid) based particles can be developed as a vehicle to deliver small molecular drugs, genes/peptides to produce a DNA vaccine/immunotherapy for autoimmune diseases and cancer.
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