Development of an in situ forming PLGA drug delivery system I. Characterization of a non-aqueous protein precipitation

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Martin Körber, Roland Bodmeier

Abstract

The incorporation of the model protein hen egg white lysozyme into liquid in situ forming poly(lactide-co-glycolide) (PLGA) implant or microparticle formulations was investigated. Ternary solvent blends of dimethyl sulfoxide (DMSO), ethyl acetate and water were used to adjust the protein solubility in order to facilitate the incorporation of either dispersed or dissolved protein into the polymer solution. Lysozyme formed large gel particles when dispersed directly in the polymer solution. These formulations had a pronounced initial release. Non-aqueous precipitation of lysozyme from solutions in DMSO with ethyl acetate led to a reversible aggregation without loss in biological activity. Lysozyme could be incorporated in a finely dispersed state through an in situ precipitation by non-solvent or polymer addition. Non-aqueous precipitation could thus be utilized to manufacture biodegradable in situ forming drug delivery systems containing homogeneously distributed and bioactive protein.

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Citations

May 28, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Milica StankovićWouter L J Hinrichs
Oct 16, 2009·Journal of the Royal Society, Interface·Marjan EnayatiMohan Edirisinghe
Jan 1, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Raghu Raj Singh ThakurDavid S Jones
Dec 29, 2013·Drug Development and Industrial Pharmacy·Muge KilicarslanRoland Bodmeier
Dec 29, 2015·International Journal of Biological Macromolecules·Zhixia GengZugong Yu
Oct 22, 2016·Drug Development and Industrial Pharmacy·Soad Ali YehiaMary Yosry Aziz
Mar 25, 2017·Journal of Pharmaceutical Sciences·Hanif HaidariSanjay Garg
Jun 23, 2015·Macromolecular Bioscience·Parker LeeJonathan Pokorski
Aug 6, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Karyn L JarvisClive A Prestidge
Aug 8, 2021·Advanced Drug Delivery Reviews·Xiaoyi Wang, Diane J Burgess
Nov 25, 2020·International Journal of Pharmaceutics·Min Sung SuhDiane J Burgess
Mar 15, 2012·International Journal of Pharmaceutics·Sonali V KapsePadma V Devarajan

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