Translating the Manufacture of Immunotherapeutic PLGA Nanoparticles from Lab to Industrial Scale: Process Transfer and In Vitro Testing

Translating the Manufacture of Immunotherapeutic PLGA Nanoparticles from Lab to Industrial Scale: Process Transfer and In Vitro Testing

Poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug delivery systems are known to offer a plethora of potential therapeutic benefits. However, challenges related to large-scale manufacturing, such as the difficulty of reproducing complex formulations and high manufacturing costs, hinder the...

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Bibliographic Details
Published in:Pharmaceutics Vol. 14; no. 8; p. 1690
Main Authors: Operti, Maria Camilla, Bernhardt, Alexander, Pots, Jeanette, Sincari, Vladimir, Jager, Eliezer, Grimm, Silko, Engel, Andrea, Benedikt, Anne, Hrubý, Martin, De Vries, Ingrid Jolanda M, Figdor, Carl G, Tagit, Oya
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01-08-2022
MDPI
Subjects:
Alzheimer's disease
Antigens
Cancer
clinical translation
drug delivery
Drug delivery systems
Drugs
Good Manufacturing Practice
Immunotherapy
Manufacturing
nanomedicine
Nanoparticles
Particle size
Peptides
Pharmaceutical research
PLGA
Polymers
Production processes
scale-up manufacturing
Severe acute respiratory syndrome coronavirus 2
Technology application
Testing
Ultrasonic imaging
Vehicles
Netherlands
United Kingdom > UK
United States > US
Germany
nanomedicine
PLGA
clinical translation
nanoparticles
scale-up manufacturing
drug delivery
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Summary:Poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug delivery systems are known to offer a plethora of potential therapeutic benefits. However, challenges related to large-scale manufacturing, such as the difficulty of reproducing complex formulations and high manufacturing costs, hinder their clinical and commercial development. In this context, a reliable manufacturing technique suitable for the scale-up production of nanoformulations without altering efficacy and safety profiles is highly needed. In this paper, we develop an inline sonication process and adapt it to the industrial scale production of immunomodulating PLGA nanovaccines developed using a batch sonication method at the laboratory scale. The investigated formulations contain three distinct synthetic peptides derived from the carcinogenic antigen New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) together with an invariant natural killer T-cell (iNKT) activator, threitolceramide-6 (IMM60). Process parameters were optimized to obtain polymeric nanovaccine formulations with a mean diameter of 150 ± 50 nm and a polydispersity index <0.2. Formulation characteristics, including encapsulation efficiencies, release profiles and in vitro functional and toxicological profiles, are assessed and statistically compared for each formulation. Overall, scale-up formulations obtained by inline sonication method could replicate the colloidal and functional properties of the nanovaccines developed using batch sonication at the laboratory scale. Both types of formulations induced specific T-cell and iNKT cell responses in vitro without any toxicity, highlighting the suitability of the inline sonication method for the continuous scale-up of nanomedicine formulations in terms of efficacy and safety.
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Present address: Department of BioInterfaces, Institute for Chemistry and Bioanalytics, School of Life Sciences, FHNW University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14081690