Synthesis and Characterization of Thiolated Nanoparticles Based on Poly (Acrylic Acid) and Algal Cell Wall Biopolymers for the Delivery of the Receptor Binding Domain from SARS-CoV-2

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2024 Jul 27

PMID 39065588

Authors

Ileana Garcia-Silva

Susan Farfan-Castro

Sergio Rosales-Mendoza

Gabriela Palestino

Affiliations

Soon will be listed here.

Abstract

The COVID-19 pandemic required great efforts to develop efficient vaccines in a short period of time. However, innovative vaccines against SARS-CoV-2 virus are needed to achieve broad immune protection against variants of concern. Polymeric-based particles can lead to innovative vaccines, serving as stable, safe and immunostimulatory antigen delivery systems. In this work, polymeric-based particles called thiolated PAA/Schizo were developed. Poly (acrylic acid) (PAA) was thiolated with cysteine ethyl ester and crosslinked with a sp. cell wall fraction under an inverse emulsion approach. Particles showed a hydrodynamic diameter of 313 ± 38 nm and negative Zeta potential. FT-IR spectra indicated the presence of coconut oil in thiolated PAA/Schizo particles, which, along with the microalgae, could contribute to their biocompatibility and bioactive properties. TGA analysis suggested strong interactions between the thiolated PAA/Schizo components. In vitro assessment revealed that thiolated particles have a higher mucoadhesiveness when compared with non-thiolated particles. Cell-based assays revealed that thiolated particles are not cytotoxic and, importantly, increase TNF-α secretion in murine dendritic cells. Moreover, immunization assays revealed that thiolated PAA/Schizo particles induced a humoral response with a more balanced IgG2a/IgG1 ratio. Therefore, thiolated PAA/Schizo particles are deemed a promising delivery system whose evaluation in vaccine prototypes is guaranteed.

References

Ramos-Vega A, Rosales-Mendoza S, Banuelos-Hernandez B, Angulo C . Prospects on the Use of sp. to Develop Oral Vaccines. Front Microbiol. 2018; 9:2506. PMC: 6209683. DOI: 10.3389/fmicb.2018.02506. View

Bonengel S, Haupstein S, Perera G, Bernkop-Schnurch A . Thiolated and S-protected hydrophobically modified cross-linked poly(acrylic acid)--a new generation of multifunctional polymers. Eur J Pharm Biopharm. 2014; 88(2):390-6. DOI: 10.1016/j.ejpb.2014.06.009. View

Romagnani S . Th1/Th2 cells. Inflamm Bowel Dis. 1999; 5(4):285-94. DOI: 10.1097/00054725-199911000-00009. View

Gunn B, Alter G . Modulating Antibody Functionality in Infectious Disease and Vaccination. Trends Mol Med. 2016; 22(11):969-982. PMC: 8767654. DOI: 10.1016/j.molmed.2016.09.002. View

Dunnhaupt S, Barthelmes J, Kollner S, Sakloetsakun D, Shahnaz G, Duregger A . Thiolated nanocarriers for oral delivery of hydrophilic macromolecular drugs. Carbohydr Polym. 2014; 117:577-584. DOI: 10.1016/j.carbpol.2014.09.078. View

Marschutz M, Bernkop-Schnurch A . Thiolated polymers: self-crosslinking properties of thiolated 450 kDa poly(acrylic acid) and their influence on mucoadhesion. Eur J Pharm Sci. 2002; 15(4):387-94. DOI: 10.1016/s0928-0987(02)00025-8. View

Maddi B, Vadlamani A, Viamajala S, Varanasi S . Quantification of Lipid Content in Oleaginous Biomass Using Thermogravimetry. Methods Mol Biol. 2019; 1995:121-129. DOI: 10.1007/978-1-4939-9484-7_6. View

Garcia-Silva I, Olvera-Sosa M, Ortega-Berlanga B, Ruiz-Rodriguez V, Palestino G, Rosales-Mendoza S . Synthesis and Characterization of Innovative Microgels Based on Polyacrylic Acid and Microalgae Cell Wall and Their Potential as Antigen Delivery Vehicles. Pharmaceutics. 2023; 15(1). PMC: 9863243. DOI: 10.3390/pharmaceutics15010133. View

Luchner M, Reinke S, Milicic A . TLR Agonists as Vaccine Adjuvants Targeting Cancer and Infectious Diseases. Pharmaceutics. 2021; 13(2). PMC: 7911620. DOI: 10.3390/pharmaceutics13020142. View

10.

Wen Z, Xu Y, Zou X, Xu Z . Chitosan nanoparticles act as an adjuvant to promote both Th1 and Th2 immune responses induced by ovalbumin in mice. Mar Drugs. 2011; 9(6):1038-1055. PMC: 3131560. DOI: 10.3390/md9061038. View

11.

Patnaik S, Gorain B, Padhi S, Choudhury H, Gabr G, Md S . Recent update of toxicity aspects of nanoparticulate systems for drug delivery. Eur J Pharm Biopharm. 2021; 161:100-119. DOI: 10.1016/j.ejpb.2021.02.010. View

12.

Habeeb A . A sensitive method for localization of disulfide containing peptides in column effluents. Anal Biochem. 1973; 56(1):60-5. DOI: 10.1016/0003-2697(73)90169-3. View

13.

Heidary M, Kaviar V, Shirani M, Ghanavati R, Motahar M, Sholeh M . A Comprehensive Review of the Protein Subunit Vaccines Against COVID-19. Front Microbiol. 2022; 13:927306. PMC: 9329957. DOI: 10.3389/fmicb.2022.927306. View

14.

Pulendran B, Arunachalam P, OHagan D . Emerging concepts in the science of vaccine adjuvants. Nat Rev Drug Discov. 2021; 20(6):454-475. PMC: 8023785. DOI: 10.1038/s41573-021-00163-y. View

15.

Gok M, Demir K, Cevher E, Ozsoy Y, Cirit U, Bacinoglu S . The effects of the thiolation with thioglycolic acid and l-cysteine on the mucoadhesion properties of the starch-graft-poly(acrylic acid). Carbohydr Polym. 2017; 163:129-136. DOI: 10.1016/j.carbpol.2017.01.065. View

16.

Grabovac V, Laffleur F, Bernkop-Schnurch A . Thiomers: Influence of molecular mass and thiol group content of poly(acrylic acid) on efflux pump inhibition. Int J Pharm. 2015; 493(1-2):374-9. DOI: 10.1016/j.ijpharm.2015.05.079. View

17.

Wajant H, Pfizenmaier K, Scheurich P . Tumor necrosis factor signaling. Cell Death Differ. 2003; 10(1):45-65. DOI: 10.1038/sj.cdd.4401189. View

18.

Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S . The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011; 1813(5):878-88. DOI: 10.1016/j.bbamcr.2011.01.034. View

19.

Souza C, de Lima D, Bastos T, de Oliveira S, Beirao B, Felix A . Microalgae Schizochytrium sp. as a source of docosahexaenoic acid (DHA): Effects on diet digestibility, oxidation and palatability and on immunity and inflammatory indices in dogs. Anim Sci J. 2019; 90(12):1567-1574. DOI: 10.1111/asj.13294. View

20.

Sarti F, Iqbal J, Muller C, Shahnaz G, Rahmat D, Bernkop-Schnurch A . Poly(acrylic acid)-cysteine for oral vitamin B12 delivery. Anal Biochem. 2011; 420(1):13-9. DOI: 10.1016/j.ab.2011.08.039. View