Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up.
Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up.
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DOI：
10.1016/j.jconrel.2021.07.012
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发表时间：
2021-09-10
期刊：
影响因子：
--
通讯作者：
Grinstaff MW
中科院分区：
文献类型：
--
作者：
Colby AH;Liu R;Doyle RP;Merting A;Zhang H;Savage N;Chu NQ;Hollister BA;McCulloch W;Burdette JE;Pearce CJ;Liu K;Oberlies NH;Colson YL;Grinstaff MW
One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate level of production, i.e., “pilot-scale” production, can be achieved. Pilot-scale production at the one-liter scale serves as a proof-of-concept that large-scale production will be possible. Here, we describe the pilot-scale production of the expansile nanoparticle (eNP) technology including verification of activity and efficacy following scaleup. We describe the challenges of sonication-based emulsification procedures and how these were overcome by use of a Microfluidizer technology. We also describe the problem-solving process that led to pre-polymerization of the nanoparticle polymer—a fundamental change from the lab-scale and previously published methods. Furthermore, we demonstrate good control over particle diameter, polydispersity and drug loading and the ability to sterilize the particles via filtration using this method. To facilitate long-term storage of these larger quantities of particles, we investigated six lyoprotectants and determined that sucrose is the most compatible with the current system. Lastly, we demonstrate that these changes to the manufacturing method do not adversely affect the swelling functionality of the particles, their highly specific localization to tumors, their non-toxicity in vivo or their efficacy in treating established intraperitoneal mesothelioma xenografts.
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影响因子：
17.1
作者：
Colby AH;Berry SM;Moran AM;Pasion KA;Liu R;Colson YL;Ruiz-Opazo N;Grinstaff MW;Herrera VL
通讯作者：
Herrera VL
影响因子：
6.7
作者：
Colby AH;Colson YL;Grinstaff MW
通讯作者：
Grinstaff MW
影响因子：
14
作者：
Liu R;Colby AH;Gilmore D;Schulz M;Zeng J;Padera RF;Shirihai O;Grinstaff MW;Colson YL
通讯作者：
Colson YL
影响因子：
15
作者：
Griset, Aaron P.;Walpole, Joseph;Grinstaff, Mark W.
通讯作者：
Grinstaff, Mark W.
DOI：
10.1016/j.jtcvs.2019.12.076
发表时间：
2020-09-01
影响因子：
6
作者：
Ngoc-Quynh Chu;Liu, Rong;Colson, Yolonda L.
通讯作者：
Colson, Yolonda L.