Translating the fabrication of protein-loaded poly(lactic-co-glycolic acid) nanoparticles from bench to scale-independent production using microfluidics

被引:61
作者
Roces, Carla B. [1 ]
Christensen, Dennis [2 ]
Perrie, Yvonne [1 ]
机构
[1] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, 161 Cathedral St, Glasgow G4 0RE, Lanark, Scotland
[2] Statens Serum Inst, Ctr Vaccine Res, Copenhagen, Denmark
基金
欧盟地平线“2020”;
关键词
Microfluidics; PLGA; Nanoparticles; Proteins; Adjuvants; Polymers; IN-VITRO; PLGA NANOPARTICLES; DELIVERY-SYSTEMS; DRUG; DEGRADATION; MICROPARTICLES; MICROSPHERES; PARTICLES; NANOPRECIPITATION; ENCAPSULATION;
D O I
10.1007/s13346-019-00699-y
中图分类号
TH7 [仪器、仪表];
学科分类号
0804 ; 080401 ; 081102 ;
摘要
In the formulation of nanoparticles, poly(lactic-co-glycolic acid) (PLGA) is commonly employed due to its Food and Drug Administration and European Medicines Agency approval for human use, its ability to encapsulate a variety of moieties, its biocompatibility and biodegradability and its ability to offer a range of controlled release profiles. Common methods for the production of PLGA particles often adopt harsh solvents, surfactants/stabilisers and in general are multi-step and time-consuming processes. This limits the translation of these drug delivery systems from bench to bedside. To address this, we have applied microfluidic processes to develop a scale-independent platform for the manufacture, purification and monitoring of nanoparticles. Thereby, the influence of various microfluidic parameters on the physicochemical characteristics of the empty and the protein-loaded PLGA particles was evaluated in combination with the copolymer employed (PLGA 85:15, 75:25 or 50:50) and the type of protein loaded. Using this rapid production process, emulsifying/stabilising agents (such as polyvinyl alcohol) are not required. We also incorporate in-line purification systems and at-line particle size monitoring. Our results demonstrate the microfluidic control parameters that can be adopted to control particle size and the impact of PLGA copolymer type on the characteristics of the produced particles. With these nanoparticles, protein encapsulation efficiency varies from 8 to 50% and is controlled by the copolymer of choice and the production parameters employed; higher flow rates, combined with medium flow rate ratios (3:1), should be adopted to promote higher protein loading (% wt/wt). In conclusion, herein, we outline the process controls for the fabrication of PLGA polymeric nanoparticles incorporating proteins in a rapid and scalable manufacturing process. Scale-independent production of polymer nanoparticles
引用
收藏
页码:582 / 593
页数:12
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