Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Industrial Scale Manufacturing and Downstream Processing of PLGA-Based Nanomedicines Suitable for Fully Continuous Operation

MC. Operti, A. Bernhardt, V. Sincari, E. Jager, S. Grimm, A. Engel, M. Hruby, CG. Figdor, O. Tagit

. 2022 ; 14 (2) : . [pub] 20220125

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22010161

Grantová podpora
PRECIOUS 686089 European Union

Despite the efficacy and potential therapeutic benefits that poly(lactic-co-glycolic acid) (PLGA) nanomedicine formulations can offer, challenges related to large-scale processing hamper their clinical and commercial development. Major hurdles for the launch of a polymeric nanocarrier product on the market are batch-to-batch variations and lack of product consistency in scale-up manufacturing. Therefore, a scalable and robust manufacturing technique that allows for the transfer of nanomedicine production from the benchtop to an industrial scale is highly desirable. Downstream processes for purification, concentration, and storage of the nanomedicine formulations are equally indispensable. Here, we develop an inline sonication process for the production of polymeric PLGA nanomedicines at the industrial scale. The process and formulation parameters are optimized to obtain PLGA nanoparticles with a mean diameter of 150 ± 50 nm and a small polydispersity index (PDI < 0.2). Downstream processes based on tangential flow filtration (TFF) technology and lyophilization for the washing, concentration, and storage of formulations are also established and discussed. Using the developed manufacturing and downstream processing technologies, production of two PLGA nanoformulations encasing ritonavir and celecoxib was achieved at 84 g/h rate. As a measure of actual drug content, encapsulation efficiencies of 49.5 ± 3.2% and 80.3 ± 0.9% were achieved for ritonavir and celecoxib, respectively. When operated in-series, inline sonication and TFF can be adapted for fully continuous, industrial-scale processing of PLGA-based nanomedicines.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22010161
003      
CZ-PrNML
005      
20220425131732.0
007      
ta
008      
220420s2022 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/pharmaceutics14020276 $2 doi
035    __
$a (PubMed)35214009
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Operti, Maria Camilla $u Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands $u Evonik Operations GmbH, Research Development & Innovation, 64293 Darmstadt, Germany $1 https://orcid.org/0000000222176096
245    10
$a Industrial Scale Manufacturing and Downstream Processing of PLGA-Based Nanomedicines Suitable for Fully Continuous Operation / $c MC. Operti, A. Bernhardt, V. Sincari, E. Jager, S. Grimm, A. Engel, M. Hruby, CG. Figdor, O. Tagit
520    9_
$a Despite the efficacy and potential therapeutic benefits that poly(lactic-co-glycolic acid) (PLGA) nanomedicine formulations can offer, challenges related to large-scale processing hamper their clinical and commercial development. Major hurdles for the launch of a polymeric nanocarrier product on the market are batch-to-batch variations and lack of product consistency in scale-up manufact $a Despite the efficacy and potential therapeutic benefits that poly lactic co glycolic acid PLGA nanomedicine formulations can offer challenges related to large scale processing hamper their clinical and commercial development Major hurdles for the launch of a polymeric nanocarrier product on the market are batch to batch variations and lack of product consistency in scale up manufacturing $a Despite the efficacy and potential therapeutic benefits that poly(lactic-co-glycolic acid) (PLGA) nanomedicine formulations can offer, challenges related to large-scale processing hamper their clinical and commercial development. Major hurdles for the launch of a polymeric nanocarrier product on the market are batch-to-batch variations and lack of product consistency in scale-up manufacturing. Therefore, a scalable and robust manufacturing technique that allows for the transfer of nanomedicine production from the benchtop to an industrial scale is highly desirable. Downstream processes for purification, concentration, and storage of the nanomedicine formulations are equally indispensable. Here, we develop an inline sonication process for the production of polymeric PLGA nanomedicines at the industrial scale. The process and formulation parameters are optimized to obtain PLGA nanoparticles with a mean diameter of 150 ± 50 nm and a small polydispersity index (PDI < 0.2). Downstream processes based on tangential flow filtration (TFF) technology and lyophilization for the washing, concentration, and storage of formulations are also established and discussed. Using the developed manufacturing and downstream processing technologies, production of two PLGA nanoformulations encasing ritonavir and celecoxib was achieved at 84 g/h rate. As a measure of actual drug content, encapsulation efficiencies of 49.5 ± 3.2% and 80.3 ± 0.9% were achieved for ritonavir and celecoxib, respectively. When operated in-series, inline sonication and TFF can be adapted for fully continuous, industrial-scale processing of PLGA-based nanomedicines.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Bernhardt, Alexander $u Evonik Operations GmbH, Research Development & Innovation, 64293 Darmstadt, Germany
700    1_
$a Sincari, Vladimir $u Institute of Macromolecular Chemistry CAS, Heyrovsky Square 2, 162 06 Prague, Czech Republic $1 https://orcid.org/000000027379066X
700    1_
$a Jager, Eliezer $u Institute of Macromolecular Chemistry CAS, Heyrovsky Square 2, 162 06 Prague, Czech Republic
700    1_
$a Grimm, Silko $u Evonik Operations GmbH, Research Development & Innovation, 64293 Darmstadt, Germany
700    1_
$a Engel, Andrea $u Evonik Corporation, Birmingham Laboratories, Birmingham, AL 35211, USA
700    1_
$a Hruby, Martin $u Institute of Macromolecular Chemistry CAS, Heyrovsky Square 2, 162 06 Prague, Czech Republic $1 https://orcid.org/000000025075261X $7 xx0060770
700    1_
$a Figdor, Carl Gustav $u Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands
700    1_
$a Tagit, Oya $u Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands $1 https://orcid.org/0000000257736647
773    0_
$w MED00186380 $t Pharmaceutics $x 1999-4923 $g Roč. 14, č. 2 (2022)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35214009 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20220420 $b ABA008
991    __
$a 20220425131729 $b ABA008
999    __
$a ind $b bmc $g 1784510 $s 1161359
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 14 $c 2 $e 20220125 $i 1999-4923 $m Pharmaceutics $n Pharmaceutics $x MED00186380
GRA    __
$a PRECIOUS 686089 $p European Union
LZP    __
$a Pubmed-20220420

Najít záznam

Citační ukazatele

Možnosti archivace