Generic placeholder image

Pharmaceutical Nanotechnology


ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Influence of Albumin in the Microfluidic Synthesis of PEG-PLGA Nanoparticles

Author(s): Bettina Poller, Gavin F. Painter and Greg F. Walker*

Volume 7, Issue 6, 2019

Page: [460 - 468] Pages: 9

DOI: 10.2174/2211738507666191023091938


Background: A key challenge in the manufacturing of polymeric colloids is producing nanoparticles with good batch-to-batch consistency.

Objective: Develop a robust microfluidics method for the preparation of PEG-PLGA nanoparticles using dimethyl sulfoxide (DMSO) as the organic phase solvent for the encapsulation of DMSO soluble agents.

Methods: Microfluidic process parameters, total flow rate (10 mL/min), flow rate ratio (1:1) of the aqueous phase and the organic polymer solution, and polymer concentration (5 mg/ml). Polyvinyl alcohol (PVA) or human serum albumin (HSA) was included in the aqueous phase. Dynamic light scattering and transmission electron microscopy were used to investigate the size and morphology of particles.

Results: PLGA nanoparticles made using DMSO with the aqueous solvent containing PVA (2%) had an average size of 60 nm while PLGA-PEG nanoparticles made with and without PVA (2%) had an average size of 70 and 100 nm, respectively. PLGA-PEG nanoparticles generated with or without PVA had a high batch-to-batch coefficient of variation for the particle size of 20% while for PLGA nanoparticles with PVA it was 4%. HSA added to the aqueous phase reduced the size and the zeta potential of PEG-PLGA nanoparticles as well the batch-to-batch coefficient of variation for particle size to < 5%. Nanoparticles were stable in solution and after lyophilized in the presence of sucrose.

Conclusion: Albumin was involved in the self-assembly of PEG-PLGA nanoparticles altering the physicochemical properties of nanoparticles. Adding protein to the aqueous phase in the microfluidic fabrication process may be a valuable tool for tuning the properties of nanoparticles and improving batch-to-batch consistency.

Keywords: Batch-to-batch reproducibility, microfludics, nanoparticles, PEG-PLGA, PEGylation, stability.

Graphical Abstract
Rezvantalab S, Drude NI, Moraveji MK, et al. PLGA-based nanoparticles in cancer treatment. Front Pharmacol 2018; 9: 1260.
[] [PMID: 30450050]
Swider E, Koshkina O, Tel J, Cruz LJ, de Vries IJM, Srinivas M. Customizing poly(lactic-co-glycolic acid) particles for biomedical applications. Acta Biomater 2018; 73: 38-51.
[] [PMID: 29653217]
Peng Q, Zhang S, Yang Q, et al. Preformed albumin corona, a protective coating for nanoparticles based drug delivery system. Biomaterials 2013; 34(33): 8521-30.
[] [PMID: 23932500]
Abdelwahed W, Degobert G, Stainmesse S, Fessi H. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Deliv Rev 2006; 58(15): 1688-713.
[] [PMID: 17118485]
Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev 2011; 63(3): 170-83.
[] [PMID: 20965219]
Abstiens K, Goepferich AM. Microfluidic manufacturing improves polydispersity of multicomponent polymeric nanoparticles. J Drug Deliv Sci Technol 2019; 49: 433-9.
Morikawa Y, Tagami T, Hoshikawa A, Ozeki T. The use of an efficient microfluidic mixing system for generating stabilized polymeric nanoparticles for controlled drug release. Biol Pharm Bull 2018; 41(6): 899-907.
[] [PMID: 29863078]
Fornaguera C, Calderó G, Mitjans M, Vinardell MP, Solans C, Vauthier C. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies. Nanoscale 2015; 7(14): 6045-58.
[] [PMID: 25766431]
Gossmann R, Fahrlander E, Hummel M, Mulac D, Brockmeyer J, Langer K. Comparative examination of adsorption of serum proteins on HSA- and PLGA-based nanoparticles using SDS-PAGE and LC-MS. Eur J Pharm Biopharm 2015; 93: 80-7.
Leroux JC, Gravel P, Balant L, et al. Internalization of poly(D,L-lactic acid) nanoparticles by isolated human leukocytes and analysis of plasma proteins adsorbed onto the particles. J Biomed Mater Res 1994; 28(4): 471-81.
[] [PMID: 8006052]
Zhang T-X, Zhu G-Y, Lu B-Y, Zhang C-L, Peng Q. Concentration-dependent protein adsorption at the nano-bio interfaces of polymeric nanoparticles and serum proteins. Nanomedicine 2017; 12(22): 2757-69.
[] [PMID: 29017387]
Cenni E, Granchi D, Avnet S, et al. Biocompatibility of poly(D,L-lactide-co-glycolide) nanoparticles conjugated with alendronate. Biomaterials 2008; 29(10): 1400-11.
[] [PMID: 18191195]
Pakulska MM, Elliott Donaghue I, Obermeyer JM, et al. Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. Sci Adv 2016; 2(5)e1600519
[] [PMID: 27386554]
Garg SM, Parmar M, Thomas A, et al. Microfluidics-based manufacture of PEG-b-PLGA block copolymer nanoparticles for the delivery of small molecule therapeutics association for pharmaceutical sciences annual meeting 2016 .Nov 13-17; Denver, Colorado.
Locatelli E, Comes Franchini M. Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system. J Nanopart Res 2012; 14(12): 1316.
Birnbaum DT, Kosmala JD, Brannon-Peppas L. Optimization of preparation techniques for poly(lactic acid-co-glycolic acid) Nanoparticles. J Nanopart Res 2000; 2(2): 173-81.
Cabra V, Arreguin R, Farrés A. Emulsifying properties of proteins. Boletín de la Sociedad Química de México 2008; 2(2): 80-9.
Cheng J, Teply BA, Sherifi I, et al. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 2007; 28(5): 869-76.
[] [PMID: 17055572]
Tuyen DTP, Nguyen TH, To VV, Ho TH, Nguyen TA, Dang MC. A new formulation of curcumin using poly (lactic-co-glycolic acid)-polyethylene glycol diblock copolymer as carrier material. Adv Nat Sci: Nanosci Nanotechnol 2014; 5(3) 035013
Vlasova IM, Saletsky AM. Study of the denaturation of human serum albumin by sodium dodecyl sulfate using the intrinsic fluorescence of albumin. J Appl Spectrosc 2009; 76(4): 536-41.
Shubhra QTH, Tóth J, Gyenis J, Feczkó T. Surface modification of HSA containing magnetic PLGA nanoparticles by poloxamer to decrease plasma protein adsorption. Colloids Surf B Biointerfaces 2014; 122: 529-36.
[] [PMID: 25092588]

© 2024 Bentham Science Publishers | Privacy Policy