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WIREs Nanomed Nanobiotechnol
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Poly(lactic‐co‐glycolic acid) devices: Production and applications for sustained protein delivery

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Injectable or implantable poly(lactic‐co‐glycolic acid) (PLGA) devices for the sustained delivery of proteins have been widely studied and utilized to overcome the necessity of repeated administrations for therapeutic proteins due to poor pharmacokinetic profiles of macromolecular therapies. These devices can come in the form of microparticles, implants, or patches depending on the disease state and route of administration. Furthermore, the release rate can be tuned from weeks to months by controlling the polymer composition, geometry of the device, or introducing additives during device fabrication. Slow‐release devices have become a very powerful tool for modern medicine. Production of these devices has initially focused on emulsion‐based methods, relying on phase separation to encapsulate proteins within polymeric microparticles. Process parameters and the effect of additives have been thoroughly researched to ensure protein stability during device manufacturing and to control the release profile. Continuous fluidic production methods have also been utilized to create protein‐laden PLGA devices through spray drying and electrospray production. Thermal processing of PLGA with solid proteins is an emerging production method that allows for continuous, high‐throughput manufacturing of PLGA/protein devices. Overall, polymeric materials for protein delivery remain an emerging field of research for the creation of single administration treatments for a wide variety of disease. This review describes, in detail, methods to make PLGA devices, comparing traditional emulsion‐based methods to emerging methods to fabricate protein‐laden devices. This article is categorized under: Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology‐Inspired Nanomaterials > Peptide‐Based Structures
Schematic diagram of protein encapsulation within poly(lactic‐co‐glycolic acid) microparticles via the double emulsion process (W/O/W)
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(a) Size exclusion chromatography chromatogram, dynamic light scattering histogram, and transmission electron micrograph image of native Qβ virus‐like particles (VLPs) showing the correct 30 nm size and icosahedral morphology. (b) Size exclusion chromatography chromatogram, dynamic light scattering histogram, and transmission electron micrograph image of Qβ VLPs after melt extrusion with PLGA showing the appearance of a small aggregate peak in the chromatogram and histogram. (c) Anti‐Qβ IgG end‐point titers and subtypes generated of mice immunized via three biweekly injections of Qβ solution, denoted “Injection,” and mice implanted once with Qβ/PLGA material, denoted “Implant.” The black arrow indicates an injection of Qβ solution for all mice to challenge the immunological memory(Lee, Shukla, et al., )
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(a) Dispersion of bovine serum albumin (BSA) within a poly(lactic‐co‐glycolic acid) (PLGA) cylinder prepared via twin‐screw extrusion and (b) in vitro release of BSA from cylinders before and after storage at 30 °C for 8 weeks. (c) Dispersion of BSA modified with hydrophobic fluorescein isothiocyanate (FITC) dye within a PLGA cylinder prepared via twin‐screw extrusion and (d) in vitro release of BSA modified with hydrophobic FITC dye from cylinders before and after storage at 30 °C for 8 weeks(Cossé et al., )
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Schematic diagram of the melt extrusion process for encapsulation of bovine serum albumin with poly(lactic‐co‐glycolic acid)(Rajagopal, Wood, Tran, Patapoff, & Nivaggioli, )
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(a) Scanning electron microscopy (SEM) micrograph and (b) size distribution histogram of poly(lactic‐co‐glycolic acid) (PLGA) microparticles prepared via coaxial electrospray. (c) Confocal microscopy image of the distribution of fluorescently labeled bovine serum albumin (BSA) within PLGA microparticles prepared via coaxial electrospray. (d) SEM micrograph and (e) size distribution histogram of PLGA microparticles prepared via coaxial electrospray. (f) Confocal microscopy image of the distribution of fluorescently labeled BSA within PLGA microparticles prepared via coaxial electrospray. Release profile of BSA from microparticles prepared via (g) emulsion and (h) coaxial electrospray with the release over the first day shown in the inset(Wang et al., )
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Schematic diagram of the electrospinning and electrospraying process with a rotating drum collector
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(a) Schematic diagram of the three‐fluid atomizer and spray drying process. (b) in vitro release profile of lysozyme from spray‐dried microspheres prepared using acetonitrile (M50F10ACN), acetone (M50F10ACE), and dichloromethane (M50F10DCM)(Wan et al., )
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Schematic diagram of inlet flows and nozzle designs for (a) two‐fluid pressure nozzle spray drying, (b) three‐fluid pressure nozzle spray drying, (c) rotary nozzle spray drying, and (d) ultrasonic nozzle spray drying
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(a) Scanning electron microscopy (SEM) micrograph of poly(lactic‐co‐glycolic acid) (PLGA) microparticles encapsulating tetanus toxoid prepared via coacervation. (b) Antibody response of mice immunized with microparticles releasing tetanus toxoid (open symbols) and tetanus toxoid adsorbed to aluminum (closed symbols) (Esparza & Kissel, ). (c) Optical image of PLGA microparticles encapsulating triptorelin during phase separation. (d) Phase diagram for PLGA microparticle formation via coacervation with the stability window shown in black(Ruiz, Tissier, & Benoit, )
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Schematic diagram of microparticle production via coacervation. The protein solution (blue) is added to the polymer (red) dissolved in the primary organic solvent (orange) and emulsified. The emulsion is then added to the primary nonsolvent (green) to induce phase separation where the polymer coalesces around the aqueous droplet and the primary solvent mixes with the primary nonsolvent. The coalesced polymer/protein droplets is then added to a secondary nonsolvent (purple) that induces further phase separation and hardening of the polymer around the inner protein‐rich phase
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(a) Table of parameters for production of liraglutide encapsulated poly(lactic‐co‐glycolic acid) (MW = 30 kDa, 50/50 lactide/glycolide) microspheres via the W/O/W emulsion process. (b) Scanning electron microscopy (SEM) micrograph of microspheres used for in vivo studies produced using parameters from serial 2. (c) in vivo plasma glucose response of rat treatment groups after sugar gavage administration. The treatment groups were: CG, negative control; HFG, positive control; LLG, single injection of microspheres containing 0.9 mg liraglutide; LMG, single injection of microspheres containing 1.8 mg liraglutide, LHG, single injection of microspheres containing 3.6 mg of liraglutide and LCIG, daily injection of 0.06 mg of liraglutide(Wu et al., )
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Biology-Inspired Nanomaterials > Peptide-Based Structures
Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Biology-Inspired Nanomaterials > Protein and Virus-Based Structures

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