AAAR 30th Annual Conference
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Da-Ren Chen

PLGA-Based Controlled Drug Delivery System Generated by a Twin-Head Electrospray

Huijing Fu, Da-Ren Chen

Washington University in St. Louis

     Abstract Number: 589
     Last modified: April 4, 2011

     Working Group: Nanoparticles and Materials Synthesis

Abstract
Drug delivery systems have evolved from traditional pills to controlled release delivery systems. Compared to traditional delivery system (TDS), controlled release drug delivery system (CRS) can increase drug effectiveness by maintaining the drug concentration in target organs at a desired level while decreasing the side effects caused by drug concentration close to the toxic threshold which is often encountered in TDS. Electrohydrodynamic atomization (Electrospray, ES) has been shown to generate polymer-coated drug particles with the diameters ranging from nanometers to micrometers. ES-generated particles are nearly monodisperse, which can be directly used in pulmonary drug delivery. High encapsulation efficiency can be achieved by well controlling the spray conditions.

A twin-head electrospray was developed to generate controlled drug delivery system. Each spray head could be operated in either single capillary or dual-capillary configuration. Positive and negative charged droplets were generated by two spray heads which were controlled separately. Charge-enhanced coagulation process also reduced the level of electrical charges carried by droplets. Biodegradable poly(lactid-co-glycolide) (PLGA) was used as the coating material. Two drugs, budesonide and pioglitazone, both of which are approved by the Food and Drug Administration (FDA) for clinical use, were coated/mixed with PLGA for the twin-head ES. The size distributions and morphology of synthesized drug were measured by scanning mobility particle sizer (SMPS) and SEM (Nova NanoSEM 2300, FEI), respectively. The release profile of synthesized drug was also characterized by high performance liquid chromatography (HPLC).

Controlled release profile can be achieved by a dual-capillary ES. By using the twin-head ES with the dual-capillary configuration for each spray head, the drug release rate can be further decreased as compared to the cases produced by one ES head. More, drug/PLGA matrix particles can be produced by using twin spray heads in single capillary configuration with one producing drug droplets and the other PLGA droplets. Oppositely charged droplets then collided to form drug/PLGA matrix particles. Our characterization of synthesized drug/PLGA matrix particles shows that their release profiles had an initial rapid release and slow zero order release.

In general droplets generated by ES processes are highly charged in the same polarity because of its DC operation. The charges on particles require to be reduced in order to minimize the electrostatic loss of droplet. The collision between oppositely charged polymer and drug droplets in the twin-head ES also served as charge-reduction process. Our experimental data shows that the particle penetration efficiency in the twin-head ES was comparable with that in the cases using two radioactive neutralizers. The drug/PLGA particles produced by twin-head ES can thus be directly used for in vivo controlled drug delivery studies in pulmonary delivery, eliminating the use of other charge reduction techniques, such as radioactive materials, corona discharge, and soft X-ray.

 
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