Background: Noscapine is a phthalideisoquinoline alkaloid obtained from opium poppy found to have anti cancer properties. The compound is well-tolerated with low toxicity profile but its clinical translation against cancer is limited due to poor dissolution characteristics, and substantial first-pass metabolism. Objective: This paper deals with the preparation, optimization and characterization of poly(D,L-lactide) nanoparticles encapsulating noscapine for its intended use as anticancer formulation. Methods: Noscapine encapsulation in biodegradable poly(D,L-lactide) nanoparticles was done by employing emulsion solvent diffusion method. A number of variables such as organic solvent, its ratio with aqueous phase, drug to polymer ratio, mixing speed were optimized. To investigate the effect of process variables on mean particle size, drug loading and entrapment efficiency of several stabilizers were also screened. In vitro noscapine release was studied using dialysis bag method. Final formulation was freeze dried for long term storage for which a number of lyoprotectants were screened. Results: It was observed that stabilizer, solvent, drug to polymer ratio, surfactant concentration, organic/aqueous phase volume ratio and stirring speed influence nanoparticle size significantly whereas drug loading and entrapment efficiency were significantly influenced by stabilizers, solvents, drug to polymer ratio and surfactant concentration. Optimized noscapineloaded PLA nanoparticles were found to be of spherical shape with mean size of 190.8±3.5nm. Drug loading and entrapment efficiency were 7.2±0.2% and 70.3±1.7% respectively. Noscapine release pattern from the prepared PLA nanoparticles was found to be biphasic with an initial burst followed by sustained release. Mannitol provided best lyoprotection to freeze dried noscapine PLA nanoparticles. Conclusion: Noscapine can be successfully formulated as poly(D,L-lactide) nanoparticles with good drug loading and encapsulation efficiency whose prolonged storage can be ensured with freeze drying.