Ultrasonic Production of Biodegradable Nanospheres0 pages

Ultrasonic Production of Biodegradable Nanospheres
Biodegradable micro- and nanospheres can be produced in a continuous, contact- and
contamination-free process that can be readily run under sterile conditions.

Introduction
Biodegradable micro- and nanospheres (MS, NS) made of poly(lactide-coglycolide) (PLGA) or
other materials are very potent drug and antigen delivery systems with inherent potential
for drug and antigen targeting. Present methods to produce PLGA NS are typical batch
processes and suffer from difficulties of upscaling under sterile conditions. Here, we present
a novel and elegant method to produce PLGA NS in a continuous, contact- and
contamination-free process that can be readily run under sterile conditions. During the
entire manufacturing process, the product is in direct contact only with sterile glass and
Teflon® tubes. The process can be run in a closed system to prevent any environmental
contamination.

Methods
PLGA50:50 nanoparticles (Resomer® RG503H, Boehringer Ingelheim) were produced using a
modified solvent extraction/evaporation process [1]. PLGA dissolved in dichloromethane (2
or 5%) was dispersed in aqueous 0.5% (w/w) PVA-solution by means of the novel
experimental set-up involving a contact-free flow-through ultrasonication cell. The coarse
O/W-dispersion was first premixed by a magnetic stirrer and then homogenized in the
ultrasonic flow-through cell (flow rates of O- and W-phases were at 1:8). The initially formed
PLGA-solvent nanodroplets gradually solidified during the passage in the tubes to become
PLGA nanoparticles. Final hardening of the particles was achieved in a larger volume of 0.5%
PVA solution.

Fig. 1: Experimental set-up for the production of PLGA nanospheres