Analysis of the controlled drug release (CDR) from biopolymer nanoparticles during the initial burst using a novel modeling method

In the initial stage of the controlled release of a drug from a nanoparticle into a medium a phenomenon referred to as burst can occur. During burst a large amount of drug is released over a small period of time. Apart from... [ view full abstract ]

In the initial stage of the controlled release of a drug from a nanoparticle into a medium a phenomenon referred to as burst can occur. During burst a large amount of drug is released over a small period of time. Apart from the loss in the overall CDR time of actuation, high initial drug release rates can result into toxic drug levels, which would not be attained otherwise. The initial burst has been studied in the past, but with little success in elucidating the mechanisms that control the phenomenon.
In this contribution, a mathematical model is established to investigate how experimental conditions and nanoparticle formulations impact on the initial burst release. Experimental conditions, nanoparticle formulations and drug release profiles were extracted from publications for drug-PLGA or -PLGA/PEG carriers and a database was created. Subsequently, statistical methods were utilized to analyze the data and a model was developed that can predict the burst release based on experimental conditions and nanoparticle formulations. Good agreement between model predictions and experimental burst data was obtained. Further analysis revealed that a clear augmentation in the quantity and kinetics of the burst is obtained when PEG is bound to PLGA. It also seems that an increase in the burst release quantity occurs for greater carrier particles, i.e. going from 5E1 nanometers towards microparticles, but at a slower rate. Longer chains of PLGA and smaller drug molecules show an enhancement on the burst rate.
The increased understanding of the burst release can in future be used to manipulate the system more rationally e.g. to reduce the intensity of the burst release.