Double emulsion process

In one study, PLG microspheres bound to DNA using a cryogenic double emulsion process and injected intramuscularly into mice were found to promote transgene expression for up to 174 days after injection, dependent upon microsphere mass. More recently nanoparticles were constructed from carboxy terminated, PEG modified PGL polymers. These particles were conjugated with an aptamer to the prostate specific membrane antigen and evaluated for in vivo biodistribution in an LNCaP (PSMA+) xenograft mouse model of prostate cancer. In this study, the aptamer caused a 3.77-fold increase in polymer concentration in the tumor tissue after retro-orbital injection (79). 

DNA polyplexes have been encapsulated and released from polymer microspheres, which may enable these microspheres to be fabricated into matrices using an approach such as the gas-foaming procedure. PLL/DNA complexes have been incorporated into PLG microspheres using a double emulsion process. DNA is incorporated with efficiencies ranging from 30% to 45%, is released over approximately 35 days, and retains its integrity [207, 208]. Alternatively ONs complexed with PEI have been incorporated and released from PLG microspheres. The release profile of the ON/PEI complexes depended on the size, loading, and pore structure of the microspheres. The sustained release of ON/PEI complexes resulted in improved intracellular penetration of the delivered vector as compared with uncom-plexed DNA [209, 210]. PLG/DNA scaffolds have successfully been used in vivo to enhance matrix deposition [113], angiogenesis [112, 113, 115], and bone formation [114]. 

To enhance encapsulation efficiency, a spray-drying method could be proposed. Thus, this technique provides a significant improvement of betamethasone encapsulation efficacy into PLGA microparticles, namely, 90% encapsulation efficacy compared with 15% for Wi/o/ W2 double emulsion process [28]. An emulsification/spray-drying technique has also been proposed as an alternative to the double emulsion method for encapsulation of peptide drug, vancomycin into microspheres for the topical ocular delivery (encapsulation efficacy 84-99%) [29]. 

Yang, R., Gao, R., Li, F., He, H., Tang, X., 2011. The infiuence of lipid characteristics on the formation, in vitro release, and in vivo absorption of protein-loaded SLN prepared by the double emulsion process. Drug Development and Industrial Pharmacy 37, 139—148. 

Fig. 4. Schematic representation of the emulsion-based microencapsulation processes the single emulsion process utilizes lyophilized drug in the first step whereas the double emulsion process utilizes an aqueous solution of the drug in the first step.

Maa YF, Hsu CC. 1997. Effect of primary emulsions on microsphere size and proteinloading in the double emulsion process. J Microencapsul 14 225-241. 

J. Bibette, F. Leal-Calderon, and P. Gorria Polydisperse Double Emulsion, Corresponding Monodisperse Double Emulsion and Process to Fabricate the Monodisperse Emulsion. Patent WOO 121297 (1999). 

In the early 1970s Li [13] proposed a method that is now called Emulsion (surfactant) Liquid Membrane (ELM) or Double Emulsion Membrane (DEM) (Fig. 3). The name reveals that the three liquid system is stabilized by an emulsifier, the amount of which reaches as much as 5 % or more with respect to the membrane liquid. The receiving phase R, which usually has a smaller volume than the donor solution, F of similar nature, is finally dispersed in the intermediate phase, M. In the next step the donor solution F is contacted with the emulsion. For this purpose, the emulsion is dispersed in the donor solution F by gentle mixing typically in a mixer-settler device. After this step, the emulsion is separated and broken. The enriched acceptor solution is further processed and the membrane liquid M is fed back for reuse. 

Bibette J, Leal Calderon F, Gorria P (1999) Polydisperse double emulsion, corresponding monodisperse double emulsion and process to fabricate the monodisperse emulsion WO0121297... 

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