Title:Noscapine-loaded PLA Nanoparticles: Systematic Study of Effect of Formulation and Process Variables on Particle Size, Drug Loading and Entrapment Efficiency
VOLUME: 3 ISSUE: 2
Author(s):Kiran Yadav, Deepak Yadav, Manisha Yadav and Sunil Kumar
Affiliation:Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana 136119, India.
Keywords:PLA, noscapine, polymeric nanoparticles, emulsification solvent diffusion method.
Abstract: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.
