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A Multiplexed Electrospray Process for Single-Step Synthesis of Stabilized Polymer Particles for Drug Delivery

A Multiplexed Electrospray Process for Single-Step Synthesis of Stabilized Polymer Particles for Drug Delivery

Begoña Almería, Tarek M Fahmy, Alessandro Gomez

J Control Release. 2011 Sep 5;154(2):203-10.

PMID: 21640147

Abstract:

While conventional methods for biodegradable particle production rely predominately on batch, emulsion preparation methods, an alternative process based on multiplexed electrospray (ES) can offer distinct advantages. These include enhanced encapsulation efficiency of hydrophilic and hydrophobic agents, scale-up potential, tight control over particle size and excellent particulate reproducibility. Here we developed a well-controlled ES process to synthesize coated biodegradable polymer particles. We demonstrate this process with the Poly(DL-lactic-co-glycolic acid) system encapsulating amphiphilic agents such as doxorubicin (DOX), Rhodamine B (RHO(B)) and Rhodamine B octadecyl ester perchlorate (RHO(BOEP)). We show that in a single-step flow process particles can be made encapsulating the agent with high efficiency and coated either with emulsifiers that stabilize them in solution or that may facilitate further functionalization for targeted drug delivery. The coating process allows for the surface modification of the particles without further changes in particle size or morphology, and with minimal loss of drug (>94% encapsulation efficiency). This synthesis technique is well suited for massive scale-up using microfabricated, multiplexed arrays consisting of multiple electrospray nozzles operating in parallel. A simple analytical model of the diffusion of the encapsulated agent within the polymer reveals two distinct phases in the cumulative release profile: a first phase in which the release is dominated by diffusion and a second phase with a slower release related to the erosion of the polymer matrix. The first, diffusion-driven stage is highly affected by particle agglomeration properties, whereas the second one shows a much less pronounced dependence on particle size. Modeling suggests that the size of the particles will substantially influence the initial burst in both the percentage of drug released and the rate at which it is released. It will also affect to a smaller extent the secondary slow and sustained release. Our study highlights the importance of tight control over particle size and morphology and the avoidance of particle aggregation for control over the release kinetics and formulation repeatability.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP142179008	Rhodamine B octadecyl ester perchlorate		142179-00-8	Price

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