The purpose of this research was to prepare Doxorubicin loaded Nanosponge gel for Sustained release of drug, increase the drug solubility, and increase the drug permeability, to reduce the dosing frequency and side effects. The FTIR studies proved that there were no interaction between the drug and Polymers. Homogenization technique followed by centrifugation was employed to prepare Nanosponge using various polymers. The formulation were prepared using different Polymers (Ethyl cellulose and Poly methyl methacrylate) in different ratios (Drug: Polymer–1:1, 1:2, 1:3, 1:4 and 1:5,) Using dichloromethane as cross linker as well as solvent. The formulations were characterized for drug entrapment efficiency. The entrapment efficiency of the formulations was observed to be from 97.85 to 99.21. The highest entrapment efficiency was observed with 99.21 and 98.94 for the formulations F3 and F7. The formulations were characterized for drug content. The Drug content of the formulations was observed to be from 82.90 to 95.71. The particle size analysis done by Malvern Zeta sizer showed that the average particle size of Doxorubicin loaded Nanosponge F3 and F7was 231.1nm and 370.3nm respectively. The SEM analysis of Nanosponge shows the spherical surface of the particles. The in-vitro release of Doxorubicin Nanosponge optimized formulation F3 was found to be 36.28% and F7 was 45.66% at the end of 24 hours. The drug content of the Gel G1and G2 was found to be 25.15% and 28.88% respectively. The in-vitro release of Doxorubicin Nanosponge Gel formulation G1was found to be 23.15% and G2 was 28.88% at the end of 24hours. The pH of the gels G1and G2 was found to be 4.89 and 4.92 respectively. The Viscosity of the gels G1 and G2 was found to be 2.939x106 cps and 2.853x106 cps respectively. It was concluded that the Doxorubicin loaded Nanosponge Gel may have increased the solubility, drug release and Antifungal activity (Increase in Zone of Inhibition), and provide sustained effect The FTIR studies proved that there were no interaction between the drug and Polymers.