Monday, October 5, 2015

Encapsulation Efficiency Determination method of mPEG-PLA nanoparticles

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers such as mPEG-PLA. Often these polymers are used for generating nanoparticles for drug release. A question I often receive is: how does one determine encapsulation efficiency for the drug loaded in the nanoparticles? It is typically not advised to load the nanoparticles directly into the HPLC. The answer depends on the pharmaceutical ingredient but typically requires disrupting the nanoparticles by dissolving them in a good polymer solvent first (such as dichloromethane) and then extracting the drug into a solvent which is appropriate for HPLC testing. An example is shown below:
Example encapsulation efficiency protocol for paclitaxel in mPEG-PLA (Y. Dong, S.-S. Feng / Biomaterials 25 (2004) 2843–2849):
“Two ml particle suspension was freeze-dried and the drug encapsulated in the lyophilized particles was determined using HPLC (Agilent LC 1100). Briefly, 3 mg particles were dissolved in 1 ml DCM under vigorous vortexing. This solution was transferred to 5 ml of the mixture of 50/50 (v/v) acetonitrile and water. The nitrogen was introduced to evaporate dicholoromethane and a clear solution was obtained for HPLC analysis. The mobile phase of HPLC was composed of acetonitrile and water of 50/50 (v/v). The measurement was performed triplicate. The EE was expressed as the percentage of the drug loaded in the final product.”
You can read more about this as well as other aspects of mPEG-PLA drug loading and delivery here: Dong, Yuancai, and Si-Shen Feng. "Methoxy poly (ethylene glycol)-poly (lactide)(MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs." Biomaterials 25, no. 14 (2004): 2843-2849. http://www.sciencedirect.com/science/article/pii/S014296120300797X
“Abstract: Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized and used to make nanoparticles by the nanoprecipitation method for clinical administration of antineoplastic drugs. Paclitaxel was used as a prototype drug due to its excellent efficacy and commercially great success. The size and size distribution, surface morphology, surface charge and surface chemistry of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, atomic force microscopy, zeta-potential analyzer and X-ray photoelectron spectroscopy (XPS). The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography. The effects of various formulation parameters were evaluated. The prepared nanoparticles were found of spherical shape with size less than 100 nm. Zeta potential measurement and XPS analysis demonstrated the presence of PEG layer on the particle surface. Viscosity of the organic phase was found to be one of the main process factors for the size determination. The EE was found to be greatly influenced by the drug loading. The drug release pattern was biphasic with a fast release rate followed by a slow one. The particle suspension exhibited good steric stability in vitro. Such a nanoparticle formulation of paclitaxel can be expected to have long-circulating effects in circulation. Keywords: AFM (atomic force microscopy); Biodegradable polymers; Chemotherapy; Taxanes; XPS (X-ray photoelectron spectroscopy)”
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