title: Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: State-of-the-art and challenges.
abstract: Poly(lactide-co-glycolide) (PLGA) microspheres are efficient delivery systems for controlled release of low molecular weight drugs as well as therapeutic macromolecules. The most common microencapsulation methods are based on emulsification procedures, in which emulsified droplets of polymer and drug solidify into microspheres when the solvent is extracted from the polymeric phase. Although high encapsulation efficiencies have been reported for hydrophobic small molecules, encapsulation of hydrophilic and/or amphiphilic small molecules is challenging due to the partitioning of drug from the polymeric phase into the external phase before solidification of the particles. This review addresses formulation-related aspects for efficient encapsulation of small hydrophilic/amphiphilic molecules into PLGA microspheres using conventional emulsification methods (e.g., oil/water, water/oil/water, solid/oil/water, water/oil/oil) and highlights novel emulsification technologies such as microfluidics, membrane emulsification and other techniques including spray drying and inkjet printing. Collectively, these novel microencapsulation technologies afford production of this type of drug loaded microspheres in a robust and well controlled manner.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands; Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Farshad
authors.initials: F
authors.lastname: Ramazani
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
authors.forename: Weiluan
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
authors.forename: Cornelis F
authors.initials: CF
authors.lastname: van Nostrum
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands; Department of Controlled Drug Delivery, University of Twente, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany; Department of Controlled Drug Delivery, University of Twente, The Netherlands.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands. Electronic address: r.j.kok@uu.nl.
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Kok
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004655:Emulsions; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D008970:Molecular Weight; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012997:Solvents / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Encapsulation efficiency; Microencapsulation; PLGA; Polymeric microspheres; Sustained release