Mesoporous Silicon Particles Favor the Induction of Long-Lived Humoral Responses in Mice to a Peptide-Based Vaccine

Abstract

Vaccinology faces the challenge of developing improved immunization approaches that are able to induce long-term immunity with the desired Th profile according to the pathology. In this context, new vehicles for efficient antigen delivery that exert adjuvant effects play a critical role in addressing this goal. Herein, mesoporous silicon particles (PSiP) were assessed as carriers for a peptide-based vaccine targeting the receptor for advanced glycation end products (RAGE), which is a relevant receptor in Alzheimer´s disease and other diseases. A RAGE peptide was adsorbed onto PSiP (PSiP vaccine) and administered to BALB/c mice, leading to immune responses that were similar in magnitude to those induced by the soluble peptide. However, the response induced by PSiP lasted for a significantly longer period when compared with the behavior of the group immunized with the peptide alone. Therefore, PSiP are proposed as carriers to enhance immune memory, which is critical in vaccination. This study opens interesting perspectives related to the application of PSiP in vaccinology.

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides

“…111,117,118 Rosales-Mendoza et al prepared a peptidebased vaccine based on negatively charged pSi nanocarriers loaded with positively charged, advanced glycation end products (RAGE) peptide, for the treatment of immune diseases such as Alzheimer's. 114 In vivo results confirmed that the SC injected peptide loaded pSiNPs increased the prolonged efficacy of immunization by significantly longer humoral responses compared to free peptide injection (up to 52 days). 114 Molecular interactions of RAGE and pSi particles at the physiologic condition were responsible for the enhancement of the immunogenic activity of RAGE.…”

“…In vivo results confirmed that the SC injected peptide loaded pSiNPs increased the prolonged efficacy of immunization by significantly longer humoral responses compared to free peptide injection (up to 52 days) . Molecular interactions of RAGE and pSi particles at the physiologic condition were responsible for the enhancement of the immunogenic activity of RAGE . In another study, Herzig et al designed thermally hydrocarbonized pSi (THCpSi) MPs with 38–53 μm size for the delivery of peptide Melanotan II .…”

“…pSi particles are a promising candidate for biomedical and drug delivery applications, particularly due to their biodegradability, tunable pore/particle size, high porosity, and high loading capacity. ,, pSi particles can protect peptides from the body’s harsh conditions such as acidic pHs (due to high acidic-pH resistance of pSi) or enzymolysis. , Facile surface functionalization of pSi with various chemistries and agents enables improved and targeted delivery with minimum side effects. ,, Rosales-Mendoza et al prepared a peptide-based vaccine based on negatively charged pSi nanocarriers loaded with positively charged, advanced glycation end products (RAGE) peptide, for the treatment of immune diseases such as Alzheimer’s . Molecular interactions of RAGE and pSi particles at the physiologic condition were responsible for the enhancement of the immunogenic activity of RAGE .…”

“…114 Molecular interactions of RAGE and pSi particles at the physiologic condition were responsible for the enhancement of the immunogenic activity of RAGE. 114 In another study, Herzig et al designed thermally hydrocarbonized pSi (THCpSi) MPs with 38−53 μm size for the delivery of peptide Melanotan II. 123 The peptide LE of 15 w/w % along with sustained release kinetics over 8 days were achieved.…”

“…Micro- and nanoparticle-based delivery platforms have been receiving considerable attention in biomedical and drug delivery applications due to their unique properties, such as high stability in the physiological environments of the body, biodegradability, tunable properties (e.g., size, physical/chemical features, hydrophobicity, surface functionalization), high permeability, − and capability to deliver water-insoluble drugs . They also provide effective protection of encapsulated biologically active therapeutic agents and control over drug dose and release kinetics from hours to months. ,,,− Moreover, particle-based delivery platforms can be designed with minimal toxicity, high drug loading capacity, and targeted delivery of peptides. ,− Furthermore, particles have been reported to encapsulate and deliver a wide range of hydrophobic and hydrophilic therapeutic peptides. , Some recent examples of novel particle platforms are liposomes/lipid-based particles, polymeric particles, porous silicon (pSi) particles, silica particles, and stimuli-responsive (linker-conjugated) particles. Several micro/nanoformulated particle platforms containing therapeutic peptides are now available in the market, such as Bydureon, a once-weekly SC injected long-acting formulation of exenatide encapsulated in 60 μm poly­(lactic- co -glycolic acid) (PLGA) microspheres and long-acting PLGA/PLA microparticle (MP) based formulations for leuprolide acetate …”