Optimization of protein precipitation for high-loading drug delivery systems for immunotherapeutics

Levi Nelemans, Aiva Simaite, Matej Buzgo
2020 Proceedings of The 1st International Electronic Conference on Pharmaceutics   unpublished
Cancer is the second leading cause of death in the world and is often untreatable. Proteinbased therapeutics, such as immunotherapeutics, show promising results in the fight against cancer, resulting in their market share increasing every year. Unfortunately, most protein-based therapeutics suffer from fast degradation in the blood, making effective treatment expensive, causing more off-target effects (due to the high doses necessary), and often require repeated injections to stay within the
more » ... stay within the correct therapeutic range. Encapsulation of these proteins inside nanocarriers is prompted to overcome these problems by enhancing targeted drug delivery and, thus, leading to a less frequent administration and lower required dose. However, most current protein encapsulation methods show very low loading capacities (LC). This leads to even more expensive treatments and might pose a further risk for the patient caused by systemic toxicity against high concentrations of the carrier material. We investigated and optimized protein nanoprecipitation as a method to obtain a high protein LC and encapsulation efficiency (EE) inside poly(lactic-co-glycolic acid; PLGA) nanoparticles via a simple two-step process. In this work, we used model proteins to investigate the influence of various parameters such as precipitation solvent, addition speed, and protein concentration on protein activity. Our work is a critical step towards the high-loading encapsulation of immunotherapeutics.
doi:10.3390/iecp2020-08683 fatcat:mbto6zq3cfa53nndxtcoq6xq2q