Transitioning Layer-by-Layer Nanocapsule Synthesis from Batch to Continuous Production: Optimizing Calcium Phosphate Core Template Encapsulation

Sam Au 1*

Continuous LbL nanocapsule production could revolutionize scalable drug delivery, enhancing targeted, efficient treatments through controlled release mechanisms.

Abstract

Background: The Layer-by-Layer (LbL) self-assembly technique, involving alternating deposition of oppositely charged polyelectrolytes on core templates, offers significant promise for enhancing drug encapsulation in targeted delivery systems. Traditional batch methods limit scalability, thus motivating this study’s focus on a continuous production process for nanocapsules using calcium phosphate (CaP) cores coated with poly(diallyldimethylammonium chloride) (PDADMAC) and poly(styrene sulfonate) (PSS). Methods: This study examined essential factors for a continuous nanoparticle production process. Single-layered CaP-PDADMAC nanoparticle synthesis was first semi-continuously optimized, focusing on PDADMAC and PSS concentration, with a deposition time determination for each layer. Comparative analyses between traditional batch, optimized batch, and continuous methods were conducted, evaluating zeta potential and particle size for stability and uniformity. Results: The optimized conditions were found to be 1 g/L for PDADMAC and 3 g/L for PSS, with a deposition time of 5 minutes per layer. Zeta potential measurements indicated values above +25 mV or below -25 mV, ensuring stability across methods. The ZetaPLUS Particle Size Analyzer confirmed a mean diameter of 88.5 nm for continuously produced 8-layered CaP-PDADMAC/PSS nanoparticles, with a relative variance of 0.273. SEM imaging validated the core dissolution and formation of hollow nanocapsules with each polyelectrolyte layer contributing an average thickness of 3.2 nm. Conclusion: The study demonstrates the viability of continuous LbL nanocapsule production, achieving consistent nanoparticle stability and size, supporting its potential in scalable drug delivery applications.

Keywords: Layer-by-Layer self-assembly, nanocapsules, polyelectrolyte layers, continuous process, drug delivery

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