Development of PLGA microparticles with high immunoglobulin G-loaded levels and sustained-release properties obtained by spray-drying a water-in-oil emulsion

Abstract

A B S T R A C TIn this study, the possibility of producing highly antibody-loaded microparticles with sustained-release properties was evaluated. Polyclonal immunoglobulin G (IgG) was used as a model of antibody and its encapsulation into poly(lactide-co-glycolide) acid (PLGA) microparticles was performed by spray-drying a water-in-oil (w/o) emulsion. It was demonstrated that the use of the Resomer ® RG505 PLGA allowed an IgG loading of 20% w/w with an encapsulation efficiency higher than 85%. The produced microparticles were characterized by a mean diameter lower than 10 µm. The burst effect was shown to reach a maximal value of 40%. IgG stability after encapsulation was also assessed. The use of this single PLGA provided a lag time of 3 months which dramatically slowed down the release rate after the initial release of the encapsulated IgG. Using blends of PLGA characterized by different inherent viscosities allowed decreasing the lag time and modulating the dissolution profile of the IgG from the spray-dried microparticles. Therefore, spray-drying a water-in-oil emulsion appeared to be a promising strategy to produce highly antibody-loaded microparticles characterized by sustained-release properties.

Development of mAb-loaded 3D-printed (FDM) implantable devices based on PLGA

“…To ensure a steady and sustained release of the loaded mAb over time, melt processing such as 3DP seemed adequate. To our knowledge, systems such as microparticles have shown high burst effects (Arrighi et al, 2019;Marquette et al, 2014). This issue could be decreased using DDS with a dense polymer matrix.…”

“…Dichloromethane was removed and the Nanosep® devices containing the mAb precipitate were placed for 1 h under vacuum to remove potential residual solvent. Then, 0.5 mL of PBS (0.2 M, pH 7.0) containing 0.02% w/w of polysorbate 80 (PS80) were added into the tube to solubilize the mAb before the solution was stirred at 600 rpm for 2 h. The Nanosep® devices were then centrifuged for 10 min at 12 000 rpm (adapted from Arrighi et al, 2019). The mAb stability was then evaluated by SEC (as described in Section 2.2.7).…”

“…microparticles and implants) are characterized by a triphasic release profiles. These phases include an initial burst effect (I), a latent phase with diffusion driven release (II) and a sustained release of the drug due to the erosion of the polymer (III) (Arrighi et al, 2019;Duque et al, 2018;Fredenberg et al, 2011). To ensure a steady and sustained release of the loaded mAb over time, melt processing such as 3DP seemed adequate.…”

PLGA sustained-release microspheres loaded with an insoluble small-molecule drug: microfluidic-based preparation, optimization, characterization, and evaluation in vitro and in vivo

“…What is more, it is necessary to adjust the size of microspheres for adapting to the standards of drug administration for different diseases. Traditional preparation methods of microspheres usually have wide particle size distribution, such as emulsification and spray drying (Arrighi et al., 2019 ; Steipel et al., 2019 ; Hsu et al., 2020 ). Therefore, it is very important to develop a technology that can accurately control the particle size and size distribution of microspheres.…”

Towards a better understanding of the release mechanisms of caffeine from PLGA microparticles

“…This type of advanced drug products allows to preprogram the release rate of the active agent into the human body after injection or implantation. Flexible release periods can be provided, for example, ranging from a few days up to several months . Controlling the “entry” rate into the human body allows optimizing the therapeutic efficacy and minimizing the risk of toxic side effects.…”