The layer-by-layer film deposition is a suitable strategy for the design and functionalization of drug carriers with superior performance, which still lacks information describing the influence of assembly conditions on the mechanisms governing the drug release process. Herein, traditional poly(acrylic acid)/poly(allylamine) polyelectrolyte multilayers (PEM) were explored as a platform to study the influence of the assembly conditions such as pH, drug loading method, and capping layer deposition on the mechanisms that control the release of calcein, the chosen model drug, from PEM. Films with 20−40 bilayers were assembled at pH 4.5 or 8.8, and the drug loading process was carried out during-or post-film assembly. Release data were fitted to three release models, namely, Higuchi, Ritger−Peppas, and Berens−Hopfenberg, to investigate the mechanism governing the drug transport, such as the apparent diffusion and the relaxation time. The postassembly drug loading method leads to a higher drug loading capacity than the during-assembly method, attributed to the washing out of calcein during film assembly steps in the latter method. Higuchi's and Ritger−Peppas' model analyses indicate that the release kinetic constant increased with the number of bilayers for the postassembly method. The opposite trend is observed for the during-assembly method. The Berens−Hopfenberg release model enabled the decoupling of each drug transport mechanism's contribution, indicating the increase of the diffusion contribution with the number of bilayers for the postassembly method at pH 4.5 and the increase of the polymer relaxation contribution for the during-assembly method at pH 8.8. Deborah's number, which represents the ratio of the polymer relaxation time to the diffusion time, follows the trends observed for the relaxation contribution for the conditions investigated. The deposition of the capping phospholipid layer over the payload also favored the polymer relaxation contribution in the drug release, featuring new strategies to investigate the drug release in PEM.

Com o objetivo de investigar a influência de parâmetros de formação nas propriedades físico-químicas de recobrimentos poliméricos produzidos pela técnica de Layer-by-Layer spin coating, foram desenvolvidos filmes contendo 10 bicamadas utilizando os pares de polieletrólitos SPS/PDAC (poli(4-estirenosulfonato de sódio) e poli(cloreto de dialildimetilamonio)) e HA/CHI (ácido hialurônico e quitosana) em substratos de silício. Foram variadas, de maneira geral, as seguintes condições: velocidade de rotação do substrato, concentração das soluções poliméricas utilizadas, grau de acetilação e pH das soluções poliméricas. Os filmes foram caracterizados via Espectroscopia de UV-Vis e Microscopia de Força Atômica (AFM) com módulos de KPFM e dC/dZ. Paralelamente, filmes de 10 e 20 bicamadas foram produzidos pelo método imersivo nas mesmas condições de concentração para fins de comparação.

The self-assembled layer-by-layer technique has attracted a great deal of attention as a method for engineering bio-functional surfaces under mild chemical conditions. The production of multilayer films, starting from newly designed building blocks, may be laborious, considering the inherent limitations for anticipating how minimal changes in the macromolecular composition may impact both film deposition and performance. This paper presents an automated, high-throughput approach to depositing polyelectrolyte multilayers (PEMs) in multiwell plates, enabling the screening of nearly 100 film formulations in the same process. This high-throughput layer-by-layer (HT-LbL) method runs in an affordable, fully commercial platform using Python-coded routines that can be easily adapted for the materials science lab settings. The HT-LbL system was validated by investigating the deposition of polysaccharide-based films in multiwell plates, probing the absorbance signal of ionically stained polyelectrolyte multilayers (PEMs) prepared in one single batch. The HT-LbL method was also used to investigate the deposition of PEMs with a small library of genetically engineered elastin-like polypeptides (ELPs) with different levels of ionizable and hydrophobic amino acid residues. The deposition of ELP/chitosan films was assessed based on the signal of fluorescently labeled species (chitosan or ELP-mCherry), demonstrating that both electrostatic and hydrophobic residues are essential for film buildup. The growth and surface properties of ELP-mCherry/chitosan films also seemed susceptible to the assembly pH, forming a higher film growth and a rougher and more hydrophobic surface for both polyelectrolytes deposited under a low ionization degree. Overall, this study illustrates the challenge of predicting the growth and properties of multilayer films and how the HT-LbL can accelerate the development of multilayer films that demand high levels of testing and optimization.