Chitosan derivatives for inactivation of endotoxins and surface protection of nanoparticles
The present disclosure provides a polymer comprising a derivative of chitosan, wherein the derivative is zwitterionic, as well as methods of using the polymer. In addition, the present disclosure provides a nanoparticle structure comprising a derivative of chitosan and a dendrimer, as well as methods of utilizing the nanoparticle structure.
1. An anti-tumor nanoparticle comprising a non-covalent, electrostatic complex between (1) a conjugate comprising a poly(amidoamine) dendrimer (PAMAM dendrimer) and an anti-tumor agent and (2) a zwitterionic chitosan derivative having an anhydride to amine (An/Am) ratio of 0.3 to 0.7, wherein (A) the zwitterionic chitosan derivative was synthesized by partial amidation of a chitosan with succinic anhydride, (B) the weight ratio of zwitterionic chitosan derivative to PAMAM dendrimer is greater than or equal to 1 but less than or equal to 4, and (C) the size of the anti-tumor nanoparticle is between 250 nm and about 500 nm.
2. The anti-tumor nanoparticle of claim 1 , wherein the PAMAM dendrimer is a generation 5 (G5) dendrimer.
3. A method of treating a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the anti-tumor nanoparticles of claim 1 .
4. A method of treating a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the anti-tumor nanoparticles of claim 2 .
5. An imaging nanoparticle comprising a non-covalent, electrostatic complex between (1) a conjugate comprising a poly(amidoamine) dendrimer (PAMAM dendrimer) and an imaging agent and (2) a zwitterionic chitosan derivative having an anhydride to amine (An/Am) ratio of 0.3 to 0.7, wherein (A) the zwitterionic chitosan derivative was synthesized by partial amidation of a chitosan with succinic anhydride, (B) the weight ratio of zwitterionic chitosan derivative to PAMAM dendrimer is greater than or equal to 1 but less than or equal to 4, and (C) the size of the imaging nanoparticle is between 250 nm and about 500 nm.
6. The imaging nanoparticle of claim 5 , wherein the PAMAM dendrimer is a generation 5 (G5) dendrimer.
7. A method of imaging a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the imaging nanoparticles of claim 5 .
8. A method of imaging a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the imaging nanoparticles of claim 6 .