Sustained protein release from hydrogel microparticles using layer-by-layer (LbL) technology

Abstract

Context and objectives: Since most of developed therapeutic proteins are intended to treat chronic diseases, patients are prescribed multiple injections for long time periods, and therefore, sustained release formulations are much needed. However, challenges facing these formulations are quite significant. In this context, a model protein, lysozyme (Lys), was loaded on hydrogel microparticles (beads) and the ability of layer-by-layer (LbL) coating to control Lys release and maintain its activity over a one-month period was investigated. Methods: LbL coating was composed of chondroitin sulfate as a negatively charged polyelectrolyte and a biocompatible, hydrolytically degradable poly b-aminoester as a positively charged polyelectrolyte. Loading distribution was monitored by fluorescence imaging, and followed by depositing a series of LbL coatings of different thicknesses. Release of Lys from these formulations was studied and activity of released fraction was determined. Results: Lys was loaded effectively on hydrogel beads achieving about 9 mg protein/100 mg wet spheres. LbL coating was proven successful by monitoring the zeta potential of the beads, which was reversed after the addition of each layer. In vitro release studies showed sustained release profiles that depend on the thickness of the deposited coat, with t 50 extended from 4.9 to 143.9 h. More importantly, released Lys possessed a high degree of biological activity during the course of release maintaining at least 72% of initial activity. Conclusions: Successful loading of Lys and extension of its release while maintaining a considerable degree of activity might make this formulation suitable for use with other active therapeutic proteins.

Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo

“…These effective DDSs are used to deliver hydrophobic or hydrophilic therapeutics which exhibit poor pharmacokinetics and high cytotoxicity to the site of tumor (Wang et al, 2016;Qin et al, 2017;Li et al, 2019). Recently, multilayered liposome-polymer NPs prepared by layer-bylayer (LbL) deposition technique appear as the more promising nano-sized carriers for targeted drug delivery and controlled release (Ariga et al, 2014;Borges & Mano, 2014;Sakr et al, 2016;Olszyna et al, 2019). LbL NPs are constituted by a functional core for drug loading, a multifunctional polyelectrolyte multilayer for drug controlled release, and a stealth layer for extended circulation time and targeting effect (Yan et al, 2011;Alotaibi et al, 2019).…”

Graphene Oxide Thin Films with Drug Delivery Function

“…Furthermore, a careful monitoring of the drug’s release profile is important. In order to access this, for the most part what happens is the incubation of the films in physiological conditions (generally PBS at 37 °C), and then the PBS solution is analyzed through various methods which might include: UV-visible/fluorescence spectroscopy to evaluate the release kinetics [ 34 , 36 , 52 , 53 , 54 ]; micro-BCA kit to evaluate loading efficiency [ 55 ]; measurement of fluorescence spectra for fluorescent molecules [ 56 ]; ELISA for release studies of some proteins [ 57 ]; and gel electrophoresis and circular dichroism (CD) spectroscopy to evaluate whether proteins released from films maintain their primary and secondary structures [ 58 , 59 ]. Notwithstanding, the erosion of a multilayered DDS can be followed using the same technique that was applied to follow the growth of the film to obtain a detailed interpretation of the drug release behavior.…”

Current Research on Polyelectrolyte Nanostructures: From Molecular Interactions to Biomedical Applications

“…They were applied as carriers for simvastatin to avoid any cytotoxic effects. Sulfonated poly(vinyl alcohol)-based hydrogel beads were decorated by electrostatically stabilized alternating multilayers of chondroitin sulfate and hydrolytically degradable poly β-aminoester in order to prevent the burst release and prolong the discharge of the model drug protein lysozyme [91].…”