Preparation and characterization of magnetic poly D, L- lactide -co-glycolic acid phenylarsine oxide nanoparticles

Chen CAI; Qin DONG; Hongpei CAI; Shen GAO

ABSTRACT

BACKGROUND:

With the development of nanotechnology, a new system for the delivery of drugs by magnetic nanovectors has been proposed. Within a magnetic field, the system can implement site-specific drug administration, thereby raising drug concentration at the lesion focus, elevate therapeutic effects, and reduce side effects.

OBJECTIVE:

To study the preparation of magnetic poly D, L-lactide-co-glycolic acid phenylarsine oxide nanoparticles (M-PLGA-PAO-NPs) and to evaluate characteristics of the prepared nanoparticles.

DESIGN:

Several factors influencing nanoparticle characteristics were selected for single-factor tests. Then, according to experimental results, and in conjunction with orthogonally designed statistics, the optimized prescription was obtained.

SETTING:

Department of Special Diagnosis, Changhai Hospital, Second Military Medical University of Chinese PLA.MATERIALS The study was performed at the Department of Pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA from January 2005 to March 2006. The reagents used were as follows phenylarsine oxide (Sigma, USA), poly D, L-lactic-co-glycolic acid (Shandong Medical Apparatus Institute, China), ferroso-ferric oxide (nanometer, Sigma, USA), polyvinyl alcohol (PVA1788, Beijing Organic Chemical Industry Plant, China). Methylene dichloride and other agents were all analytical grade and purchased from Shanghai Sinopharm Chemical Reagent Co., Ltd, China.

METHODS:

M-PLGA-PAO-NPs were prepared through an emulsion-evaporation process. Nanoparticle shape was observed by transmission electron microscopy. Magnetism was determined by a vibrating sample magnetometer. The size and diametral distribution of nanoparticles were determined by a laser particle size analyzer. The encapsulation ratio and drug loading of phenylarsine were measured by high performance liquid chromatography (HPLC). The percentage of phenylarsine oxide release in vitro was calculated [the percentage of phenylarsine oxide release in vitro =(total dose of phenylarsine oxide-residual dose of phenylarsine oxide)/ total dose of phenylarsine oxide].MAIN OUTCOME

MEASURES:

The shape, size, drug loading, encapsulation ratio and release in vitro of M-PLGA-PAO-NPs.

RESULTS:

The prepared nanoparticles had an average encapsulation ratio of 34.2%. Drug loading of 5 batches of nanoparticles was 3.06%, 3.15%, 3.18%, 3.21%, and 3.41%, respectively, with an average drug loading of 3.20%. Drug loading difference was small between batches, indicating good stability and reproducibility of the technology. M-PLGA-PAO-NPs were spherical, smooth, evenly distributed and non-adhesive. Ferrosoferric oxide microparticles, which exhibited unevenly dispersed black opacities, were found in the magnetic microparticles. Nanoparticles were in a narrow size range, with an average diameter of 290 nm (range 140-500 nm). When the magnitude and the direction of the outside magnetic field were changed, nanoparticles showed different intensities of magnetization. This indicated that M-PLGA-PAO-NPs had a certain magnetic response. The in vitro nanoparticle-release curve indicated that drug release was initially fast followed by a slow controlled release, and on day 8, it was basically stable.

CONCLUSION:

The experiment acquires a satisfactory technique for preparation of M-PLGA-PAO-NPs. The prepared M-PLGA-PAO-NPs were well targeted and exhibited slowly controlled drug release effects.