Hydrophilic nanostructured membrane active antimicrobials with high activity, selectivity and biodegradability
The present invention includes compositions and methods of making hydrophilic nanostructured antibiotics (i.e. nanoantibiotics), including nanoantibiotics that use environmentally degradable biomolecules as the backbone building blocks, wherein the backbone building blocks can include spherical backbones such as sucroses, cyclodextrins, glycogens, and phytoglycogen with different diameters, or rod-like backbone building blocks such as dextrins, amyloses, and celluloses with different lengths. These hydrophilic nanoantibiotics with well-defined sizes and shapes can selectively disrupt bacterial membranes (i.e., serve as membrane-active antimicrobials) while being benign to mammalian cells. Depending on the size and shape difference of the hydrophilic nanoantibiotics, they can also selectively kill one type of bacteria (e.g., gram-negative) over another type (e.g., gram-positive). The environmentally degradable nanoantibiotics will have built-in dismantling “switches” to dismantle and become antimicrobial inactive in responsive to environmental stimuli once released into natural habitat, hence greatly reducing the possibility of developing bacteria resistance.
1. A method of making biodegradable spherical polymer molecular brushes (PMBs) with specific structures and high hydrophilicity via controlled polymerization methods comprising:
wherein the spherical backbone is a biodegradable polymer and the hydrophilic polymer brushes are poly(2-(trimethylamino)ethyl methacrylate) (PTMAEMA).
2. The method of claim 1 , wherein the length n is 1 to 20, 20 to 40, 40 to 60, 60 to 80, 80 to 100, or more than 100.
3. The method of claim 1 , wherein X is selected from Cl or Br.
4. The method of claim 1 , wherein a spherical backbone is selected from at least one of sucroses, cyclodextrins, glycogens, phytoglycogen or other environmentally degradable molecules.
5. The method of claim 1 , wherein the hydrophilic polymer brushes further comprise poly(4-vinyl-N methylpyridine iodide) (P4MVP), or other polyelectrolytes including polyester and polypeptides.
6. The method of claim 1 , wherein the PMB at least one of: selectively disrupts bacterial membranes while not disrupting mammalian cell membranes, is environmentally degradable, has antimicrobial activity while in use in an animal but is dismantled into antimicrobially inactive pieces when released into a natural habitat, is a nanostructure that is either a nanorod or a nanosphere, or is formulated in a pharmaceutically acceptable carrier in an amount effective to reduce or eliminate a bacterial infection.